SPECIAL ARTICLE

How Academia and the Pharmaceutical IndustryCan Work TogetherThe Presidentrsquos Lecture Annual Meeting of the American Thoracic SocietySan Francisco California

Michael Rosenblatt1

1Merck Whitehouse Station New Jersey

Abstract

There is a long history of productive collaboration betweenbiomedical scientists in academia and in the pharmaceuticalindustry The primary beneficiary of this collaboration has been thepublic Since the middle of the last century marked advances in thetreatment and prevention of disease have been driven by thetranslational research interactions across these two domains But

now at a time when collaboration between academia and industryshould be accelerating based on past success new technology andever-increasing need numerous obstacles to effective collaborationhave appeared In this analysis based on experience in bothacademia and industry the author provides perspective on currentobstacles to academicndashindustrial collaboration followed byrecommendations on how effective collaboration can be renewedand enhanced

(Received in original form September 11 2012 accepted in final form October 29 2012 )

Correspondence and requests for reprints should be addressed to Michael Rosenblatt MD Chief Medical Officer MerckWS3A-20 One Merck Drive Whitehouse Station NJ 08889 Email michaelrosenblattmerckcom

Ann Am Thorac Soc Vol 10 No 1 pp 31ndash38 Feb 2013Copyright ordf 2013 by the American Thoracic SocietyDOI 101513AnnalsATS201209-075PSInternet address wwwatsjournalsorg

Introduction

I want to thank Nicholas Hill MD and theAmerican Thoracic Society (ATS) for givingme the honor of the invitation to deliverthe 2012 Presidentrsquos Lecture

I have spent portions of my career inboth academia and the pharmaceuticalindustry Having done academic researcheducated medical students and participatedin industry drug discovery and developmentefforts I have developed ideas about howacademia and industry should intersectHere I share my thoughts about researchcollaboration between academia and thepharmaceutical industry

A tradition of collaboration betweenacademia and the pharmaceutical industrybegan with the era of modern therapeuticsAmong many possible examples there aretwo with great relevance to respiratorymedicine One is the discovery and clinicalapplication of corticosteroids recognized

with the award of a Nobel Prize to PhilipHench (Mayo Clinic) Tadeus Reichstein(Basel University) and Edward Kendall(Mayo Clinic) (1) The process for large-scale synthesis of cortisone for use inclinical trials was developed by a team atMerck led by Lew Sarrett (2) Anothercollaboration was initiated by SelmanWaksman (Rutgers University) who wonthe Nobel Prize in 1952 for the discovery ofstreptomycin (3) He persuaded GeorgeMerck to establish a production plant thatprovided the streptomycin used by SirGeoffrey Marshall (Medical Research CouncilUnited Kingdom) in what is regarded as thefirst randomized clinical trial (4)

My colleagues and I would very muchlike to see this tradition of collaborationbetween academia and industry continuedas it is of great benefit to our patients Butthe world has changed dramatically sincethe time when steroid hormones andantibiotics were being identified and tested

as therapies Here I review currentchallenges facing industry including ourongoing search for innovation to spurinvention of new medicines and vaccinesI will explain the vital role academia playsin industryrsquos mission to generate noveltherapeutic agents identify some obstaclesto collaboration and then describe newmodels for collaboration between the twodomains

Although I am aware that this journalhas an international readership made upof individuals who are primarily eitheracademically or industrially oriented someof the proposals herein are directedspecifically at American colleagues inacademia

The Nature of Drug Invention

The pharmaceutical industry lives andbreathes translational research There are

Special Article 31

few organizations on the planet that can dowhat it has successfully accomplishedrepeatedly transform knowledge ofa potential drug target into a medicine forpatients around the world

What the pharmaceutical industry doesis often referred to as drug discovery But tome that conjures an image of two oldprospectors in a mine Onersquos shovel hitssomething hard and he says ldquoCrsquomon overhere Joe Tell me if you think what I hit isa drugrdquo In the past natural molecules thatbecame drugs were typically discoveredserendipitously But today drugs areinvented targets are selected moleculessynthesized and their properties testedthen after safety assessment means forformulation and production are devisedThere is a long cycle from idea to productFor comparison it takes about three timesas long to invent a drug as it takes to createan iPad or an iPhone (compare Figure 1with Reference 5) It is estimated that thepharmaceutical industry spends about $1billion to $2 billion to invent each newdrug (6) Merckrsquos annual investment inresearch and development (RampD) (7) isabout eight times that of Apple (8) on apercent of revenue basis

Outlined in Figure 1 is the process ofinventing a drug The first half of theprocess begins after years of basic scienceresearch in academia that leads to theidentification of potential targets for druginvention (Figure 1) Once the drug target

is validated industry spends the next 3 to6 years screening compound collections ornatural products then synthesizing newmolecules and testing them in biologicalassays that represent various aspects ofhealthy and diseased states This includesin vitro testing and evaluation in animalmodels believed to be predictive ofresponses in human disease and extensivesafety testing If successful an equalamount of time is taken evaluatingpromising molecules in clinical trials andpreparing for their large-scale productionThe failure rate at this stage is high 80 ofmolecules that enter clinical testing do notbecome drugs In addition review byregulatory agencies typically takes 1additional year The total time required toinvent a drug from identification of thecompound to full regulatory approval isgenerally 10 to 15 years With increasingfrequency there also is a period of time inwhich clinical trials and active surveillancecontinue postapproval The process ischallenging intellectually economicallyorganizationally and emotionally Butwhen successful lives are saved andsuffering is alleviated Figure 2 shows twoexamples of major drug inventions thatresulted in great success on a public healthscale

The number of deaths related tocardiovascular disease in the United Stateswas increasing in runawaymode up until the1970s Then in the 1980s a variety of

innovations including the introduction ofstatins reversed this trend Since that timecardiovascular mortality in the developedworld has been in decline (Figure 2A)

Similarly AIDS had become a deadlyglobal epidemic by the mid-1990s Theinvention of anti-HIV medicines by thepharmaceutical industry transformed thisnearly universally fatal infection intoa largely chronic disease that people in manyparts of the world now live with while theyreturn to work and lead nearly normal lives(Figure 2B)

Both of these examples are great publichealth victories resulting fromcollaborations between academia andindustry There are many more examplesPerhaps the best examples are vaccineswhich have saved the lives of millionsmostly children in the last 60 years Fewreaders of this article have not benefitedfrom a medicine or vaccine invented by thepharmaceutical industry in collaborationwith academic colleagues

The PharmaceuticalIndustry Today

Figure 3 shows an important dynamicwithin the pharmaceutical industry over thelast 3 decades Annual expenditure forRampD relative to income from sales (bars inFigure 3) has increased nearly every yearover the last 3 decades but the return on

Figure 1 The research and development process IND = Investigational New Drug Application Mfg = manufacture NDA = New Drug ApplicationAdapted by permission from Reference 21

32 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

capitalized RampD investment (dotted line inFigure 3) has decreased When I startedworking in the pharmaceutical industry inthe early 1980s $1 invested in capitalizedresearch returned about $3 (in sales) Thistook 10 to 15 years but there was a clearpositive return on investment across theindustry Roughly 30 years later thefinancial picture is very differentcapitalized RampD returned only $083 per $1invested This is not a sustainable businessmodel and it has major implications forfinancing innovation to address unmetmedical needs

Another perspective on productivity isshown in Figure 4 It displays theproductivity of three of the oldest andlargest pharmaceutical companiesmdashMerckLilly and Rochemdashover the last 60 years Forall three companies productivity (as

measured by approved new compounds)has remained generally constant at a rate ofapproximately one compound per companyper year

Consider the progress that has beenmade in our understanding of thecomplexity of biological systems and in thesophistication of our methodologies duringthe last 60 years Compare it with theproductivity of the pharmaceutical industryLook back at 1950 A drug approved in 1950was likely to have been conceived in the late1930s and developed in the 1940s In the1940s drug invention consisted of chemistsmaking compounds and administeringthem to animals in hopes of detectinga physiological response Thirty years laterin the 1970s and 1980s we entered theperiod of having true molecular targetsenzymes receptors and channels That time

is perceived as a golden age for thepharmaceutical industry What happened toproductivity at that time There was nochange compared with previous decadeseach company continued to produceapproximately one compound per year Twomore decades have passed We are now inthe era of ldquoomicsrdquo (genomics proteomicsetc) yet the yield of new medicinesremains approximately one compound percompany per year

The businessmodel of the pharmaceuticalindustry is relentlessly challenging Majorproducts in companiesrsquo portfolios todaywill be gone approximately 10 years fromnow because of patent expiry so thesecompanies need to reinvent themselvesevery decade Today pharmaceuticalcompanies fund research through revenuesderived from marketed drugs that are

Figure 2 Invention of therapeutic drugs contributes to reduction in deaths from cardiovascular disease (A) and AIDS (B) A Adapted by permission fromReference 22 B Adapted by permission from Reference 23

Figure 3 Research and development (RampD) spendsales and salescapitalized RampD for top pharmaceutical companies 1980ndash2008 Note The capitalizedRampD analysis is sales for a given yearRampD spend for 11 years (adjusted for inflation) Adapted by permission from Reference 24

Special Article 33

SPECIAL ARTICLE

based on RampD initiated 15 to 20 years agoResearch decisions made by companyleadership 10 to 15 years ago determinetodayrsquos picture And whatever positiona company will occupy in the ecosystem10 to 15 years from now will depend ondecisions that companyrsquos leaders aremaking today

The Rationalefor Collaboration

The pharmaceutical industryrsquos businessmodel depends on innovation but there isnow a growing divide in innovationstrategies within the industry Somecompanies plan to invest in their ownresearch engine at levels proportionatelysimilar to the past Merck is one suchcompany Others are backing away notwilling to take the risk inherent in long-term commitment to internal research andseeking innovation only externally It willbe years before we know the outcome ofthis big experiment But despite differentapproaches to RampD all majorpharmaceutical companies continuelooking to academia for sources ofinnovation beyond their own internalresearch engine

Why is there a need for researchcollaboration between the pharmaceuticalindustry and academia Academia andindustry have substantive differences butthey share the common goal of improvingthe health of our patients Industry relies onacademia for basic research that identifiesnovel molecular targets and for clinical trials

that evaluate the efficacy and safety ofinventions from industry Industry does nothave the vast basic research laboratoriesand hospitals that exist in academiaConversely academia is reliant on industryfor the medicines and technologies that ituses to take care of patients In additionmuch of the research funding receivedby academia is part of a covenant withgovernments and the people that discoveriesby academia will be whenever possibletranslated to improve health In a wayacademia and the pharmaceutical industryhave complementary enterprises Currentlya $33 billion National Institutes of Health(NIH) budget funds mostly basic researchalong with translational and clinical researchIn contrast research supported by industry ismostly clinical and translational with lessspent on basic research

Over the last 2 decades the relativeamount of research supported by the NIHcompared with that supported by thepharmaceutical industry has changeddramatically In the early 1990s the NIHand industry contributed approximatelyequally to supporting biomedical researchnow the pharmaceutical industry spends 25to 30 more on research than the NIH (910) This also means there are now moreresearch career opportunities in thepharmaceutical industry than in the past

Not only is there a naturalcomplementarity between academia and thepharmaceutical industry that should lead tocollaboration but collaboration is the law ofthe land at least in the United States TheBayh-Dole Act (PL 96-517 Patent andTrademark Act Amendments of 1980) is

more than 30 years old It obligatesacademic institutions that receive federalfunding for research to collaborate withindustry if they make a discovery that couldbenefit the health of the American publicThe legislation was crafted by Congressbecause many discoveries made throughpublic support were left sitting on the shelfNow the NIH clearly endorses collaborationwith industry in its Clinical TranslationalSciences Institutes and in the new NationalCenter for Advancing TranslationalSciences

Impediments to Collaboration

Before focusing attention on mechanismsfor improving research collaborations I willaddress several barriers that must beovercome First I acknowledge that theinterface between the pharmaceuticalindustry and practicing physicians has beenproblematic in the past and continues to bea source of tension and distrust This cancreate an obstacle to research collaborationsbecause some of the negative attitudesregarding this interface spill overinappropriately in my view into the arena ofresearch

Research-related relationships betweenthe pharmaceutical industry and academiaare already considerable and understoodto be essential in translating the discoveriesof basic biological research into newtherapies Organizations like ResearchAmerica have documented the publicrsquosendorsement of such collaboration (11)But there is a dissonance in understandingthe need for such collaborations and theirendorsement Attending a Jewish weddingI realized that a scene before me(Figure 5) illustrated the state of academiandashindustry relations

The community wants us to ldquodancetogetherrdquo (to collaborate) and beproductive But as in the wedding scenewhere the couple holds a handkerchiefbetween them we are not supposed totouch each other I believe academia andindustry need to find practical anddurable solutions for the best and mostappropriate ways to ldquodance togetherrdquo to beproductive without ldquotouchingrdquo

Academia has had conflict of interestrules for decades but the rules seem to be ina perpetual process of being rewritten Weneed to be mindful that constant andunpredictable change creates a regulatory

Figure 4 Cumulative new molecular entities (NMEs) produced by three large pharmaceuticalcompanies over 57 years Adapted by permission from Reference 25

34 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

vacuum A prolonged process ofmodification without ultimate resolutioncreates continuing uncertainty which keepsgood people on the sideline There isa second barrier to research collaborationsEach academic institution has its ownpolicy concerning collaboration withindustry but the language of most policies issimilar Would it be possible for a groupof universities or pharmaceuticalcompanies or both to create a universaltemplate Some would still need to beindividually negotiated such as royaltyrates payments and other items that arespecific to a particular collaboration But theavailability of a widely adopted templatecould increase efficiency and speed research

A third barrier is the growingawareness of the irreproducibility of somedata from academia (12 13) This isa problem for all who work in basicresearch Scientists at Bayer recentlyevaluated about 70 targets that they hadworked on They observed that for almosttwo-thirds of the targets the initial basicresearch data that prompted interest couldnot be replicated (14) A few months laterAmgen corroborated this finding with itsown observations (15) Venture capitalfirms do not start new companies until theyhave replicated relevant data (16) Thisproblem needs to be addressed I think theNIH and academic institutions should takeresponsibility for solving the problemThose who do deal with it directly will be inan advantaged position to collaborate withindustry

A fourth barrier is ldquored taperdquo Anysuccessful translational research continuum

requires a strong clinical researchcomponent But clinical research in certainparts of the world is in crisis Between 2002and 2007 there was a reduction byapproximately one-half in the number ofEuropean products in clinical trials that hadbeen developed in the United Kingdom(17) In 2004 6 of patients participatingin clinical trials globally did so in theUnited Kingdom But by 2008 this haddeclined to 2 to 3 (17) It has beensuggested that the reason is too muchbureaucracy (17) In the United Kingdom itnow takes almost 2 years from the timea decision is made to undertake a trialuntil the first patient enrolls The UnitedStates is not far behind we have longstartup times high dropout rates andfrequent failure to meet recruiting targets(18) Another discouraging observation isthat much time and money is spenttraining clinical investigators but almosthalf of them drop out after their firstclinical trial (18) so most first-timeinvestigators are last-time investigatorsThe environment can be so problematicand frustrating that even the NIH is off-shoring clinical trials (18)

Figure 6 shows a dramatic example ofthe changing geography of clinical trialsThe map shows the locations of sites fortwo of Merckrsquos Phase III clinical trials Oneof these trials performed in the 1990s used58 sites in 20 countries Another similartrial begun in 2009 used 387 sites in 40countries with proportionately many fewerUnited States sites

The clinical trials laboratory is nowglobal I wonder how many American

academic institutions see this picture clearlyThe US biomedical research enterprise isthe envy of the world others are looking forevery opportunity to replicate or usurp itFor example when former PresidentGeorge W Bush outlawed certain kinds ofstem cell research much of it migratedoverseas to the United Kingdom Singaporeand elsewhere with astonishing speedWe need to realize that American academicresearch institutions and globalpharmaceutical companies do not forma closed system The pharmaceuticalindustry which is sensitive to inefficienciesinappropriate barriers and practices andpolicies that slow entry of the first patientinto a trial is free and obliged to operatearound the world

How to Move Forward

I believe it is critically important forindustry and academia to collaboratebecause there remains so much unmet needin most areas of medicine In thoracicmedicine alone we do not yet have idealtherapies for chronic obstructive pulmonarydisease interstitial lung disease asthmalung cancer and pulmonary hypertensionOther areas of respiratory medicine havingunmet needs include AIDS multidrug-resistant tuberculosis and a variety ofldquoorphan diseasesrdquo

Despite all the tensions potentialconflicts of interest and regulatory issuesthat I describe above industryndashacademicpartnerships are at an all-time highFigure 7 shows a timeline of collaborationsestablished between January 2010 andFebruary 2012

Most of these collaborativearrangements differ from those of the pastwhich were large programmaticcollaborations embracing entire therapeuticareas but which for the most part wereunproductive Instead more focused and inmany ways more thoughtful models areevolving Joint steering committees decidewhat will be pursued and what will bepostponed and how much funding shouldbe allocated Instead of saying ldquohere isa check for 3 years come back and tell uswhat you found at the end of that timerdquomoney is now being released based onmilestones Sometimes academia is beingasked to ldquohave some skin in the gamerdquo ordefer rewards And industry is bringing notonly funding to collaborations but also core

Figure 5 A Jewish wedding dancing together without touching

Special Article 35

SPECIAL ARTICLE

Figure 6 Clinical trials go global Red stars identify cities where clinical trials of alendronate took place in the mid-1990s red dots identify cities whereclinical trials of odanacatib took place from 2009ndash2012

36 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

resources like genetically altered micechemical libraries and cutting-edgeimaging methods

For example a new model that Merckhas just initiated is the California Institutefor Biomedical Research (Calibr) Calibr isan independent not-for-profit organizationstartedMarch 2012 in San Diego CaliforniaMerck has made a $92 million commitmentto Calibr over the next 7 years Calibr willprovide academic collaborators with a rangeof industry infrastructure support such ascompound screening and medicinalchemistry Any investigator in any countryin the world can approach Calibr If theirproject or lead or target is accepted Calibrwill collaborate to bring the concept to proofof principle Proof of principle will triggera decision by Merck to become a formalcollaborator or to decline interest and returnto the academic institution and Calibr therights to the potential product

Another example is Pfizerrsquos Centers forTherapeutic Innovation (CTI) located inBoston New York City San Francisco andSan Diego and focused on the developmentof biologic therapies CTI research staffincludes both Pfizer employees andacademic scientists in some casescolocated in the same facility In additionto financial resources CTI provides

investigators access to select Pfizercompound libraries proprietary screeningmethods and antibody developmenttechnologies CTI will enable academiccareer advancement through research andpublication while creating significantfinancial opportunities through milestonesand royalties

In yet another collaboration thisbetween Gilead Sciences and Yale School ofMedicine scientists from both organizationswill work together to identify novel cancertherapies Gilead is providing $40 million inresearch support and basic scienceinfrastructure development during theinitial 4-year period of the collaborationGilead will provide a total of up to $100million over 10 years should thecollaboration be extended through that timeframe Gilead will have the first option tolicense Yale inventions that result from thecollaboration

What can be done to improve theclimate for clinical trials in the UnitedStates I recently coauthored a paper for anInstitute of Medicine report on clinical trials(18) We concluded that as the UnitedStates is reconfiguring the delivery ofmedical care under healthcare reform wehave an opportunity to include ldquoclinicalresearchrdquo in the business plan of new

entities such as accountable careorganizations A small tax on healthcare-related revenues could help support thisresearch In addition it is critical formedical students and trainees to beeducated in the importance and conduct ofclinical research

The leadership of the ATS has beenquite explicit in endorsing the views oncollaboration between industry andacademia espoused by the AmericanCongress and the NIH The Past-Presidentof the ATS Dr Nicholas Hill and hiscolleagues have stated ldquosuccessfulcollaborative efforts across academiagovernment and industry benefit usdaily We believe it is important for theATS to rededicate itself to fosteringa scientific culture that valuesinclusivenessmdasha scientific community ofexcellencerdquo (19) We encourage otherprofessional societies to adopt policiessimilar to that of the ATS

New Opportunitiesfor Collaboration

There are many opportunities for industryndashacademia collaborations in areas that areprecompetitive (genomics biomarkers

Figure 7 Recently formalized academiandashindustry partnerships BMS = Bristol-Myers Squibb Calibr = California Institute for Biomedical Research disc =discovery DTMI = Duke Translational Medical Institute GSK = GlaxoSmithKline JV = joint venture M = million POC = proof of concept RampD = researchand development UCB = University of California Berkeley UCSF = University of California San Francisco Wash Univ = Washington University in StLouis (Provided by and used with permission of Dr Robert M Califf Duke University Medical Center)

Special Article 37

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

capitalized RampD investment (dotted line inFigure 3) has decreased When I startedworking in the pharmaceutical industry inthe early 1980s $1 invested in capitalizedresearch returned about $3 (in sales) Thistook 10 to 15 years but there was a clearpositive return on investment across theindustry Roughly 30 years later thefinancial picture is very differentcapitalized RampD returned only $083 per $1invested This is not a sustainable businessmodel and it has major implications forfinancing innovation to address unmetmedical needs

Another perspective on productivity isshown in Figure 4 It displays theproductivity of three of the oldest andlargest pharmaceutical companiesmdashMerckLilly and Rochemdashover the last 60 years Forall three companies productivity (as

measured by approved new compounds)has remained generally constant at a rate ofapproximately one compound per companyper year

Consider the progress that has beenmade in our understanding of thecomplexity of biological systems and in thesophistication of our methodologies duringthe last 60 years Compare it with theproductivity of the pharmaceutical industryLook back at 1950 A drug approved in 1950was likely to have been conceived in the late1930s and developed in the 1940s In the1940s drug invention consisted of chemistsmaking compounds and administeringthem to animals in hopes of detectinga physiological response Thirty years laterin the 1970s and 1980s we entered theperiod of having true molecular targetsenzymes receptors and channels That time

is perceived as a golden age for thepharmaceutical industry What happened toproductivity at that time There was nochange compared with previous decadeseach company continued to produceapproximately one compound per year Twomore decades have passed We are now inthe era of ldquoomicsrdquo (genomics proteomicsetc) yet the yield of new medicinesremains approximately one compound percompany per year

The businessmodel of the pharmaceuticalindustry is relentlessly challenging Majorproducts in companiesrsquo portfolios todaywill be gone approximately 10 years fromnow because of patent expiry so thesecompanies need to reinvent themselvesevery decade Today pharmaceuticalcompanies fund research through revenuesderived from marketed drugs that are

Figure 2 Invention of therapeutic drugs contributes to reduction in deaths from cardiovascular disease (A) and AIDS (B) A Adapted by permission fromReference 22 B Adapted by permission from Reference 23

Figure 3 Research and development (RampD) spendsales and salescapitalized RampD for top pharmaceutical companies 1980ndash2008 Note The capitalizedRampD analysis is sales for a given yearRampD spend for 11 years (adjusted for inflation) Adapted by permission from Reference 24

Special Article 33

SPECIAL ARTICLE

based on RampD initiated 15 to 20 years agoResearch decisions made by companyleadership 10 to 15 years ago determinetodayrsquos picture And whatever positiona company will occupy in the ecosystem10 to 15 years from now will depend ondecisions that companyrsquos leaders aremaking today

The Rationalefor Collaboration

The pharmaceutical industryrsquos businessmodel depends on innovation but there isnow a growing divide in innovationstrategies within the industry Somecompanies plan to invest in their ownresearch engine at levels proportionatelysimilar to the past Merck is one suchcompany Others are backing away notwilling to take the risk inherent in long-term commitment to internal research andseeking innovation only externally It willbe years before we know the outcome ofthis big experiment But despite differentapproaches to RampD all majorpharmaceutical companies continuelooking to academia for sources ofinnovation beyond their own internalresearch engine

Why is there a need for researchcollaboration between the pharmaceuticalindustry and academia Academia andindustry have substantive differences butthey share the common goal of improvingthe health of our patients Industry relies onacademia for basic research that identifiesnovel molecular targets and for clinical trials

that evaluate the efficacy and safety ofinventions from industry Industry does nothave the vast basic research laboratoriesand hospitals that exist in academiaConversely academia is reliant on industryfor the medicines and technologies that ituses to take care of patients In additionmuch of the research funding receivedby academia is part of a covenant withgovernments and the people that discoveriesby academia will be whenever possibletranslated to improve health In a wayacademia and the pharmaceutical industryhave complementary enterprises Currentlya $33 billion National Institutes of Health(NIH) budget funds mostly basic researchalong with translational and clinical researchIn contrast research supported by industry ismostly clinical and translational with lessspent on basic research

Over the last 2 decades the relativeamount of research supported by the NIHcompared with that supported by thepharmaceutical industry has changeddramatically In the early 1990s the NIHand industry contributed approximatelyequally to supporting biomedical researchnow the pharmaceutical industry spends 25to 30 more on research than the NIH (910) This also means there are now moreresearch career opportunities in thepharmaceutical industry than in the past

Not only is there a naturalcomplementarity between academia and thepharmaceutical industry that should lead tocollaboration but collaboration is the law ofthe land at least in the United States TheBayh-Dole Act (PL 96-517 Patent andTrademark Act Amendments of 1980) is

more than 30 years old It obligatesacademic institutions that receive federalfunding for research to collaborate withindustry if they make a discovery that couldbenefit the health of the American publicThe legislation was crafted by Congressbecause many discoveries made throughpublic support were left sitting on the shelfNow the NIH clearly endorses collaborationwith industry in its Clinical TranslationalSciences Institutes and in the new NationalCenter for Advancing TranslationalSciences

Impediments to Collaboration

Before focusing attention on mechanismsfor improving research collaborations I willaddress several barriers that must beovercome First I acknowledge that theinterface between the pharmaceuticalindustry and practicing physicians has beenproblematic in the past and continues to bea source of tension and distrust This cancreate an obstacle to research collaborationsbecause some of the negative attitudesregarding this interface spill overinappropriately in my view into the arena ofresearch

Research-related relationships betweenthe pharmaceutical industry and academiaare already considerable and understoodto be essential in translating the discoveriesof basic biological research into newtherapies Organizations like ResearchAmerica have documented the publicrsquosendorsement of such collaboration (11)But there is a dissonance in understandingthe need for such collaborations and theirendorsement Attending a Jewish weddingI realized that a scene before me(Figure 5) illustrated the state of academiandashindustry relations

The community wants us to ldquodancetogetherrdquo (to collaborate) and beproductive But as in the wedding scenewhere the couple holds a handkerchiefbetween them we are not supposed totouch each other I believe academia andindustry need to find practical anddurable solutions for the best and mostappropriate ways to ldquodance togetherrdquo to beproductive without ldquotouchingrdquo

Academia has had conflict of interestrules for decades but the rules seem to be ina perpetual process of being rewritten Weneed to be mindful that constant andunpredictable change creates a regulatory

Figure 4 Cumulative new molecular entities (NMEs) produced by three large pharmaceuticalcompanies over 57 years Adapted by permission from Reference 25

34 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

vacuum A prolonged process ofmodification without ultimate resolutioncreates continuing uncertainty which keepsgood people on the sideline There isa second barrier to research collaborationsEach academic institution has its ownpolicy concerning collaboration withindustry but the language of most policies issimilar Would it be possible for a groupof universities or pharmaceuticalcompanies or both to create a universaltemplate Some would still need to beindividually negotiated such as royaltyrates payments and other items that arespecific to a particular collaboration But theavailability of a widely adopted templatecould increase efficiency and speed research

A third barrier is the growingawareness of the irreproducibility of somedata from academia (12 13) This isa problem for all who work in basicresearch Scientists at Bayer recentlyevaluated about 70 targets that they hadworked on They observed that for almosttwo-thirds of the targets the initial basicresearch data that prompted interest couldnot be replicated (14) A few months laterAmgen corroborated this finding with itsown observations (15) Venture capitalfirms do not start new companies until theyhave replicated relevant data (16) Thisproblem needs to be addressed I think theNIH and academic institutions should takeresponsibility for solving the problemThose who do deal with it directly will be inan advantaged position to collaborate withindustry

A fourth barrier is ldquored taperdquo Anysuccessful translational research continuum

requires a strong clinical researchcomponent But clinical research in certainparts of the world is in crisis Between 2002and 2007 there was a reduction byapproximately one-half in the number ofEuropean products in clinical trials that hadbeen developed in the United Kingdom(17) In 2004 6 of patients participatingin clinical trials globally did so in theUnited Kingdom But by 2008 this haddeclined to 2 to 3 (17) It has beensuggested that the reason is too muchbureaucracy (17) In the United Kingdom itnow takes almost 2 years from the timea decision is made to undertake a trialuntil the first patient enrolls The UnitedStates is not far behind we have longstartup times high dropout rates andfrequent failure to meet recruiting targets(18) Another discouraging observation isthat much time and money is spenttraining clinical investigators but almosthalf of them drop out after their firstclinical trial (18) so most first-timeinvestigators are last-time investigatorsThe environment can be so problematicand frustrating that even the NIH is off-shoring clinical trials (18)

Figure 6 shows a dramatic example ofthe changing geography of clinical trialsThe map shows the locations of sites fortwo of Merckrsquos Phase III clinical trials Oneof these trials performed in the 1990s used58 sites in 20 countries Another similartrial begun in 2009 used 387 sites in 40countries with proportionately many fewerUnited States sites

The clinical trials laboratory is nowglobal I wonder how many American

academic institutions see this picture clearlyThe US biomedical research enterprise isthe envy of the world others are looking forevery opportunity to replicate or usurp itFor example when former PresidentGeorge W Bush outlawed certain kinds ofstem cell research much of it migratedoverseas to the United Kingdom Singaporeand elsewhere with astonishing speedWe need to realize that American academicresearch institutions and globalpharmaceutical companies do not forma closed system The pharmaceuticalindustry which is sensitive to inefficienciesinappropriate barriers and practices andpolicies that slow entry of the first patientinto a trial is free and obliged to operatearound the world

How to Move Forward

I believe it is critically important forindustry and academia to collaboratebecause there remains so much unmet needin most areas of medicine In thoracicmedicine alone we do not yet have idealtherapies for chronic obstructive pulmonarydisease interstitial lung disease asthmalung cancer and pulmonary hypertensionOther areas of respiratory medicine havingunmet needs include AIDS multidrug-resistant tuberculosis and a variety ofldquoorphan diseasesrdquo

Despite all the tensions potentialconflicts of interest and regulatory issuesthat I describe above industryndashacademicpartnerships are at an all-time highFigure 7 shows a timeline of collaborationsestablished between January 2010 andFebruary 2012

Most of these collaborativearrangements differ from those of the pastwhich were large programmaticcollaborations embracing entire therapeuticareas but which for the most part wereunproductive Instead more focused and inmany ways more thoughtful models areevolving Joint steering committees decidewhat will be pursued and what will bepostponed and how much funding shouldbe allocated Instead of saying ldquohere isa check for 3 years come back and tell uswhat you found at the end of that timerdquomoney is now being released based onmilestones Sometimes academia is beingasked to ldquohave some skin in the gamerdquo ordefer rewards And industry is bringing notonly funding to collaborations but also core

Figure 5 A Jewish wedding dancing together without touching

Special Article 35

SPECIAL ARTICLE

Figure 6 Clinical trials go global Red stars identify cities where clinical trials of alendronate took place in the mid-1990s red dots identify cities whereclinical trials of odanacatib took place from 2009ndash2012

36 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

resources like genetically altered micechemical libraries and cutting-edgeimaging methods

For example a new model that Merckhas just initiated is the California Institutefor Biomedical Research (Calibr) Calibr isan independent not-for-profit organizationstartedMarch 2012 in San Diego CaliforniaMerck has made a $92 million commitmentto Calibr over the next 7 years Calibr willprovide academic collaborators with a rangeof industry infrastructure support such ascompound screening and medicinalchemistry Any investigator in any countryin the world can approach Calibr If theirproject or lead or target is accepted Calibrwill collaborate to bring the concept to proofof principle Proof of principle will triggera decision by Merck to become a formalcollaborator or to decline interest and returnto the academic institution and Calibr therights to the potential product

Another example is Pfizerrsquos Centers forTherapeutic Innovation (CTI) located inBoston New York City San Francisco andSan Diego and focused on the developmentof biologic therapies CTI research staffincludes both Pfizer employees andacademic scientists in some casescolocated in the same facility In additionto financial resources CTI provides

investigators access to select Pfizercompound libraries proprietary screeningmethods and antibody developmenttechnologies CTI will enable academiccareer advancement through research andpublication while creating significantfinancial opportunities through milestonesand royalties

In yet another collaboration thisbetween Gilead Sciences and Yale School ofMedicine scientists from both organizationswill work together to identify novel cancertherapies Gilead is providing $40 million inresearch support and basic scienceinfrastructure development during theinitial 4-year period of the collaborationGilead will provide a total of up to $100million over 10 years should thecollaboration be extended through that timeframe Gilead will have the first option tolicense Yale inventions that result from thecollaboration

What can be done to improve theclimate for clinical trials in the UnitedStates I recently coauthored a paper for anInstitute of Medicine report on clinical trials(18) We concluded that as the UnitedStates is reconfiguring the delivery ofmedical care under healthcare reform wehave an opportunity to include ldquoclinicalresearchrdquo in the business plan of new

entities such as accountable careorganizations A small tax on healthcare-related revenues could help support thisresearch In addition it is critical formedical students and trainees to beeducated in the importance and conduct ofclinical research

The leadership of the ATS has beenquite explicit in endorsing the views oncollaboration between industry andacademia espoused by the AmericanCongress and the NIH The Past-Presidentof the ATS Dr Nicholas Hill and hiscolleagues have stated ldquosuccessfulcollaborative efforts across academiagovernment and industry benefit usdaily We believe it is important for theATS to rededicate itself to fosteringa scientific culture that valuesinclusivenessmdasha scientific community ofexcellencerdquo (19) We encourage otherprofessional societies to adopt policiessimilar to that of the ATS

New Opportunitiesfor Collaboration

There are many opportunities for industryndashacademia collaborations in areas that areprecompetitive (genomics biomarkers

Figure 7 Recently formalized academiandashindustry partnerships BMS = Bristol-Myers Squibb Calibr = California Institute for Biomedical Research disc =discovery DTMI = Duke Translational Medical Institute GSK = GlaxoSmithKline JV = joint venture M = million POC = proof of concept RampD = researchand development UCB = University of California Berkeley UCSF = University of California San Francisco Wash Univ = Washington University in StLouis (Provided by and used with permission of Dr Robert M Califf Duke University Medical Center)

Special Article 37

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

based on RampD initiated 15 to 20 years agoResearch decisions made by companyleadership 10 to 15 years ago determinetodayrsquos picture And whatever positiona company will occupy in the ecosystem10 to 15 years from now will depend ondecisions that companyrsquos leaders aremaking today

The Rationalefor Collaboration

The pharmaceutical industryrsquos businessmodel depends on innovation but there isnow a growing divide in innovationstrategies within the industry Somecompanies plan to invest in their ownresearch engine at levels proportionatelysimilar to the past Merck is one suchcompany Others are backing away notwilling to take the risk inherent in long-term commitment to internal research andseeking innovation only externally It willbe years before we know the outcome ofthis big experiment But despite differentapproaches to RampD all majorpharmaceutical companies continuelooking to academia for sources ofinnovation beyond their own internalresearch engine

Why is there a need for researchcollaboration between the pharmaceuticalindustry and academia Academia andindustry have substantive differences butthey share the common goal of improvingthe health of our patients Industry relies onacademia for basic research that identifiesnovel molecular targets and for clinical trials

that evaluate the efficacy and safety ofinventions from industry Industry does nothave the vast basic research laboratoriesand hospitals that exist in academiaConversely academia is reliant on industryfor the medicines and technologies that ituses to take care of patients In additionmuch of the research funding receivedby academia is part of a covenant withgovernments and the people that discoveriesby academia will be whenever possibletranslated to improve health In a wayacademia and the pharmaceutical industryhave complementary enterprises Currentlya $33 billion National Institutes of Health(NIH) budget funds mostly basic researchalong with translational and clinical researchIn contrast research supported by industry ismostly clinical and translational with lessspent on basic research

Over the last 2 decades the relativeamount of research supported by the NIHcompared with that supported by thepharmaceutical industry has changeddramatically In the early 1990s the NIHand industry contributed approximatelyequally to supporting biomedical researchnow the pharmaceutical industry spends 25to 30 more on research than the NIH (910) This also means there are now moreresearch career opportunities in thepharmaceutical industry than in the past

Not only is there a naturalcomplementarity between academia and thepharmaceutical industry that should lead tocollaboration but collaboration is the law ofthe land at least in the United States TheBayh-Dole Act (PL 96-517 Patent andTrademark Act Amendments of 1980) is

more than 30 years old It obligatesacademic institutions that receive federalfunding for research to collaborate withindustry if they make a discovery that couldbenefit the health of the American publicThe legislation was crafted by Congressbecause many discoveries made throughpublic support were left sitting on the shelfNow the NIH clearly endorses collaborationwith industry in its Clinical TranslationalSciences Institutes and in the new NationalCenter for Advancing TranslationalSciences

Impediments to Collaboration

Before focusing attention on mechanismsfor improving research collaborations I willaddress several barriers that must beovercome First I acknowledge that theinterface between the pharmaceuticalindustry and practicing physicians has beenproblematic in the past and continues to bea source of tension and distrust This cancreate an obstacle to research collaborationsbecause some of the negative attitudesregarding this interface spill overinappropriately in my view into the arena ofresearch

Research-related relationships betweenthe pharmaceutical industry and academiaare already considerable and understoodto be essential in translating the discoveriesof basic biological research into newtherapies Organizations like ResearchAmerica have documented the publicrsquosendorsement of such collaboration (11)But there is a dissonance in understandingthe need for such collaborations and theirendorsement Attending a Jewish weddingI realized that a scene before me(Figure 5) illustrated the state of academiandashindustry relations

The community wants us to ldquodancetogetherrdquo (to collaborate) and beproductive But as in the wedding scenewhere the couple holds a handkerchiefbetween them we are not supposed totouch each other I believe academia andindustry need to find practical anddurable solutions for the best and mostappropriate ways to ldquodance togetherrdquo to beproductive without ldquotouchingrdquo

Academia has had conflict of interestrules for decades but the rules seem to be ina perpetual process of being rewritten Weneed to be mindful that constant andunpredictable change creates a regulatory

Figure 4 Cumulative new molecular entities (NMEs) produced by three large pharmaceuticalcompanies over 57 years Adapted by permission from Reference 25

34 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

vacuum A prolonged process ofmodification without ultimate resolutioncreates continuing uncertainty which keepsgood people on the sideline There isa second barrier to research collaborationsEach academic institution has its ownpolicy concerning collaboration withindustry but the language of most policies issimilar Would it be possible for a groupof universities or pharmaceuticalcompanies or both to create a universaltemplate Some would still need to beindividually negotiated such as royaltyrates payments and other items that arespecific to a particular collaboration But theavailability of a widely adopted templatecould increase efficiency and speed research

A third barrier is the growingawareness of the irreproducibility of somedata from academia (12 13) This isa problem for all who work in basicresearch Scientists at Bayer recentlyevaluated about 70 targets that they hadworked on They observed that for almosttwo-thirds of the targets the initial basicresearch data that prompted interest couldnot be replicated (14) A few months laterAmgen corroborated this finding with itsown observations (15) Venture capitalfirms do not start new companies until theyhave replicated relevant data (16) Thisproblem needs to be addressed I think theNIH and academic institutions should takeresponsibility for solving the problemThose who do deal with it directly will be inan advantaged position to collaborate withindustry

A fourth barrier is ldquored taperdquo Anysuccessful translational research continuum

requires a strong clinical researchcomponent But clinical research in certainparts of the world is in crisis Between 2002and 2007 there was a reduction byapproximately one-half in the number ofEuropean products in clinical trials that hadbeen developed in the United Kingdom(17) In 2004 6 of patients participatingin clinical trials globally did so in theUnited Kingdom But by 2008 this haddeclined to 2 to 3 (17) It has beensuggested that the reason is too muchbureaucracy (17) In the United Kingdom itnow takes almost 2 years from the timea decision is made to undertake a trialuntil the first patient enrolls The UnitedStates is not far behind we have longstartup times high dropout rates andfrequent failure to meet recruiting targets(18) Another discouraging observation isthat much time and money is spenttraining clinical investigators but almosthalf of them drop out after their firstclinical trial (18) so most first-timeinvestigators are last-time investigatorsThe environment can be so problematicand frustrating that even the NIH is off-shoring clinical trials (18)

Figure 6 shows a dramatic example ofthe changing geography of clinical trialsThe map shows the locations of sites fortwo of Merckrsquos Phase III clinical trials Oneof these trials performed in the 1990s used58 sites in 20 countries Another similartrial begun in 2009 used 387 sites in 40countries with proportionately many fewerUnited States sites

The clinical trials laboratory is nowglobal I wonder how many American

academic institutions see this picture clearlyThe US biomedical research enterprise isthe envy of the world others are looking forevery opportunity to replicate or usurp itFor example when former PresidentGeorge W Bush outlawed certain kinds ofstem cell research much of it migratedoverseas to the United Kingdom Singaporeand elsewhere with astonishing speedWe need to realize that American academicresearch institutions and globalpharmaceutical companies do not forma closed system The pharmaceuticalindustry which is sensitive to inefficienciesinappropriate barriers and practices andpolicies that slow entry of the first patientinto a trial is free and obliged to operatearound the world

How to Move Forward

I believe it is critically important forindustry and academia to collaboratebecause there remains so much unmet needin most areas of medicine In thoracicmedicine alone we do not yet have idealtherapies for chronic obstructive pulmonarydisease interstitial lung disease asthmalung cancer and pulmonary hypertensionOther areas of respiratory medicine havingunmet needs include AIDS multidrug-resistant tuberculosis and a variety ofldquoorphan diseasesrdquo

Despite all the tensions potentialconflicts of interest and regulatory issuesthat I describe above industryndashacademicpartnerships are at an all-time highFigure 7 shows a timeline of collaborationsestablished between January 2010 andFebruary 2012

Most of these collaborativearrangements differ from those of the pastwhich were large programmaticcollaborations embracing entire therapeuticareas but which for the most part wereunproductive Instead more focused and inmany ways more thoughtful models areevolving Joint steering committees decidewhat will be pursued and what will bepostponed and how much funding shouldbe allocated Instead of saying ldquohere isa check for 3 years come back and tell uswhat you found at the end of that timerdquomoney is now being released based onmilestones Sometimes academia is beingasked to ldquohave some skin in the gamerdquo ordefer rewards And industry is bringing notonly funding to collaborations but also core

Figure 5 A Jewish wedding dancing together without touching

Special Article 35

SPECIAL ARTICLE

Figure 6 Clinical trials go global Red stars identify cities where clinical trials of alendronate took place in the mid-1990s red dots identify cities whereclinical trials of odanacatib took place from 2009ndash2012

36 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

resources like genetically altered micechemical libraries and cutting-edgeimaging methods

For example a new model that Merckhas just initiated is the California Institutefor Biomedical Research (Calibr) Calibr isan independent not-for-profit organizationstartedMarch 2012 in San Diego CaliforniaMerck has made a $92 million commitmentto Calibr over the next 7 years Calibr willprovide academic collaborators with a rangeof industry infrastructure support such ascompound screening and medicinalchemistry Any investigator in any countryin the world can approach Calibr If theirproject or lead or target is accepted Calibrwill collaborate to bring the concept to proofof principle Proof of principle will triggera decision by Merck to become a formalcollaborator or to decline interest and returnto the academic institution and Calibr therights to the potential product

Another example is Pfizerrsquos Centers forTherapeutic Innovation (CTI) located inBoston New York City San Francisco andSan Diego and focused on the developmentof biologic therapies CTI research staffincludes both Pfizer employees andacademic scientists in some casescolocated in the same facility In additionto financial resources CTI provides

investigators access to select Pfizercompound libraries proprietary screeningmethods and antibody developmenttechnologies CTI will enable academiccareer advancement through research andpublication while creating significantfinancial opportunities through milestonesand royalties

In yet another collaboration thisbetween Gilead Sciences and Yale School ofMedicine scientists from both organizationswill work together to identify novel cancertherapies Gilead is providing $40 million inresearch support and basic scienceinfrastructure development during theinitial 4-year period of the collaborationGilead will provide a total of up to $100million over 10 years should thecollaboration be extended through that timeframe Gilead will have the first option tolicense Yale inventions that result from thecollaboration

What can be done to improve theclimate for clinical trials in the UnitedStates I recently coauthored a paper for anInstitute of Medicine report on clinical trials(18) We concluded that as the UnitedStates is reconfiguring the delivery ofmedical care under healthcare reform wehave an opportunity to include ldquoclinicalresearchrdquo in the business plan of new

entities such as accountable careorganizations A small tax on healthcare-related revenues could help support thisresearch In addition it is critical formedical students and trainees to beeducated in the importance and conduct ofclinical research

The leadership of the ATS has beenquite explicit in endorsing the views oncollaboration between industry andacademia espoused by the AmericanCongress and the NIH The Past-Presidentof the ATS Dr Nicholas Hill and hiscolleagues have stated ldquosuccessfulcollaborative efforts across academiagovernment and industry benefit usdaily We believe it is important for theATS to rededicate itself to fosteringa scientific culture that valuesinclusivenessmdasha scientific community ofexcellencerdquo (19) We encourage otherprofessional societies to adopt policiessimilar to that of the ATS

New Opportunitiesfor Collaboration

There are many opportunities for industryndashacademia collaborations in areas that areprecompetitive (genomics biomarkers

Figure 7 Recently formalized academiandashindustry partnerships BMS = Bristol-Myers Squibb Calibr = California Institute for Biomedical Research disc =discovery DTMI = Duke Translational Medical Institute GSK = GlaxoSmithKline JV = joint venture M = million POC = proof of concept RampD = researchand development UCB = University of California Berkeley UCSF = University of California San Francisco Wash Univ = Washington University in StLouis (Provided by and used with permission of Dr Robert M Califf Duke University Medical Center)

Special Article 37

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

vacuum A prolonged process ofmodification without ultimate resolutioncreates continuing uncertainty which keepsgood people on the sideline There isa second barrier to research collaborationsEach academic institution has its ownpolicy concerning collaboration withindustry but the language of most policies issimilar Would it be possible for a groupof universities or pharmaceuticalcompanies or both to create a universaltemplate Some would still need to beindividually negotiated such as royaltyrates payments and other items that arespecific to a particular collaboration But theavailability of a widely adopted templatecould increase efficiency and speed research

A third barrier is the growingawareness of the irreproducibility of somedata from academia (12 13) This isa problem for all who work in basicresearch Scientists at Bayer recentlyevaluated about 70 targets that they hadworked on They observed that for almosttwo-thirds of the targets the initial basicresearch data that prompted interest couldnot be replicated (14) A few months laterAmgen corroborated this finding with itsown observations (15) Venture capitalfirms do not start new companies until theyhave replicated relevant data (16) Thisproblem needs to be addressed I think theNIH and academic institutions should takeresponsibility for solving the problemThose who do deal with it directly will be inan advantaged position to collaborate withindustry

A fourth barrier is ldquored taperdquo Anysuccessful translational research continuum

requires a strong clinical researchcomponent But clinical research in certainparts of the world is in crisis Between 2002and 2007 there was a reduction byapproximately one-half in the number ofEuropean products in clinical trials that hadbeen developed in the United Kingdom(17) In 2004 6 of patients participatingin clinical trials globally did so in theUnited Kingdom But by 2008 this haddeclined to 2 to 3 (17) It has beensuggested that the reason is too muchbureaucracy (17) In the United Kingdom itnow takes almost 2 years from the timea decision is made to undertake a trialuntil the first patient enrolls The UnitedStates is not far behind we have longstartup times high dropout rates andfrequent failure to meet recruiting targets(18) Another discouraging observation isthat much time and money is spenttraining clinical investigators but almosthalf of them drop out after their firstclinical trial (18) so most first-timeinvestigators are last-time investigatorsThe environment can be so problematicand frustrating that even the NIH is off-shoring clinical trials (18)

Figure 6 shows a dramatic example ofthe changing geography of clinical trialsThe map shows the locations of sites fortwo of Merckrsquos Phase III clinical trials Oneof these trials performed in the 1990s used58 sites in 20 countries Another similartrial begun in 2009 used 387 sites in 40countries with proportionately many fewerUnited States sites

The clinical trials laboratory is nowglobal I wonder how many American

academic institutions see this picture clearlyThe US biomedical research enterprise isthe envy of the world others are looking forevery opportunity to replicate or usurp itFor example when former PresidentGeorge W Bush outlawed certain kinds ofstem cell research much of it migratedoverseas to the United Kingdom Singaporeand elsewhere with astonishing speedWe need to realize that American academicresearch institutions and globalpharmaceutical companies do not forma closed system The pharmaceuticalindustry which is sensitive to inefficienciesinappropriate barriers and practices andpolicies that slow entry of the first patientinto a trial is free and obliged to operatearound the world

How to Move Forward

I believe it is critically important forindustry and academia to collaboratebecause there remains so much unmet needin most areas of medicine In thoracicmedicine alone we do not yet have idealtherapies for chronic obstructive pulmonarydisease interstitial lung disease asthmalung cancer and pulmonary hypertensionOther areas of respiratory medicine havingunmet needs include AIDS multidrug-resistant tuberculosis and a variety ofldquoorphan diseasesrdquo

Despite all the tensions potentialconflicts of interest and regulatory issuesthat I describe above industryndashacademicpartnerships are at an all-time highFigure 7 shows a timeline of collaborationsestablished between January 2010 andFebruary 2012

Most of these collaborativearrangements differ from those of the pastwhich were large programmaticcollaborations embracing entire therapeuticareas but which for the most part wereunproductive Instead more focused and inmany ways more thoughtful models areevolving Joint steering committees decidewhat will be pursued and what will bepostponed and how much funding shouldbe allocated Instead of saying ldquohere isa check for 3 years come back and tell uswhat you found at the end of that timerdquomoney is now being released based onmilestones Sometimes academia is beingasked to ldquohave some skin in the gamerdquo ordefer rewards And industry is bringing notonly funding to collaborations but also core

Figure 5 A Jewish wedding dancing together without touching

Special Article 35

SPECIAL ARTICLE

Figure 6 Clinical trials go global Red stars identify cities where clinical trials of alendronate took place in the mid-1990s red dots identify cities whereclinical trials of odanacatib took place from 2009ndash2012

36 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

resources like genetically altered micechemical libraries and cutting-edgeimaging methods

For example a new model that Merckhas just initiated is the California Institutefor Biomedical Research (Calibr) Calibr isan independent not-for-profit organizationstartedMarch 2012 in San Diego CaliforniaMerck has made a $92 million commitmentto Calibr over the next 7 years Calibr willprovide academic collaborators with a rangeof industry infrastructure support such ascompound screening and medicinalchemistry Any investigator in any countryin the world can approach Calibr If theirproject or lead or target is accepted Calibrwill collaborate to bring the concept to proofof principle Proof of principle will triggera decision by Merck to become a formalcollaborator or to decline interest and returnto the academic institution and Calibr therights to the potential product

Another example is Pfizerrsquos Centers forTherapeutic Innovation (CTI) located inBoston New York City San Francisco andSan Diego and focused on the developmentof biologic therapies CTI research staffincludes both Pfizer employees andacademic scientists in some casescolocated in the same facility In additionto financial resources CTI provides

investigators access to select Pfizercompound libraries proprietary screeningmethods and antibody developmenttechnologies CTI will enable academiccareer advancement through research andpublication while creating significantfinancial opportunities through milestonesand royalties

In yet another collaboration thisbetween Gilead Sciences and Yale School ofMedicine scientists from both organizationswill work together to identify novel cancertherapies Gilead is providing $40 million inresearch support and basic scienceinfrastructure development during theinitial 4-year period of the collaborationGilead will provide a total of up to $100million over 10 years should thecollaboration be extended through that timeframe Gilead will have the first option tolicense Yale inventions that result from thecollaboration

What can be done to improve theclimate for clinical trials in the UnitedStates I recently coauthored a paper for anInstitute of Medicine report on clinical trials(18) We concluded that as the UnitedStates is reconfiguring the delivery ofmedical care under healthcare reform wehave an opportunity to include ldquoclinicalresearchrdquo in the business plan of new

entities such as accountable careorganizations A small tax on healthcare-related revenues could help support thisresearch In addition it is critical formedical students and trainees to beeducated in the importance and conduct ofclinical research

The leadership of the ATS has beenquite explicit in endorsing the views oncollaboration between industry andacademia espoused by the AmericanCongress and the NIH The Past-Presidentof the ATS Dr Nicholas Hill and hiscolleagues have stated ldquosuccessfulcollaborative efforts across academiagovernment and industry benefit usdaily We believe it is important for theATS to rededicate itself to fosteringa scientific culture that valuesinclusivenessmdasha scientific community ofexcellencerdquo (19) We encourage otherprofessional societies to adopt policiessimilar to that of the ATS

New Opportunitiesfor Collaboration

There are many opportunities for industryndashacademia collaborations in areas that areprecompetitive (genomics biomarkers

Figure 7 Recently formalized academiandashindustry partnerships BMS = Bristol-Myers Squibb Calibr = California Institute for Biomedical Research disc =discovery DTMI = Duke Translational Medical Institute GSK = GlaxoSmithKline JV = joint venture M = million POC = proof of concept RampD = researchand development UCB = University of California Berkeley UCSF = University of California San Francisco Wash Univ = Washington University in StLouis (Provided by and used with permission of Dr Robert M Califf Duke University Medical Center)

Special Article 37

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

Figure 6 Clinical trials go global Red stars identify cities where clinical trials of alendronate took place in the mid-1990s red dots identify cities whereclinical trials of odanacatib took place from 2009ndash2012

36 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

resources like genetically altered micechemical libraries and cutting-edgeimaging methods

For example a new model that Merckhas just initiated is the California Institutefor Biomedical Research (Calibr) Calibr isan independent not-for-profit organizationstartedMarch 2012 in San Diego CaliforniaMerck has made a $92 million commitmentto Calibr over the next 7 years Calibr willprovide academic collaborators with a rangeof industry infrastructure support such ascompound screening and medicinalchemistry Any investigator in any countryin the world can approach Calibr If theirproject or lead or target is accepted Calibrwill collaborate to bring the concept to proofof principle Proof of principle will triggera decision by Merck to become a formalcollaborator or to decline interest and returnto the academic institution and Calibr therights to the potential product

Another example is Pfizerrsquos Centers forTherapeutic Innovation (CTI) located inBoston New York City San Francisco andSan Diego and focused on the developmentof biologic therapies CTI research staffincludes both Pfizer employees andacademic scientists in some casescolocated in the same facility In additionto financial resources CTI provides

investigators access to select Pfizercompound libraries proprietary screeningmethods and antibody developmenttechnologies CTI will enable academiccareer advancement through research andpublication while creating significantfinancial opportunities through milestonesand royalties

In yet another collaboration thisbetween Gilead Sciences and Yale School ofMedicine scientists from both organizationswill work together to identify novel cancertherapies Gilead is providing $40 million inresearch support and basic scienceinfrastructure development during theinitial 4-year period of the collaborationGilead will provide a total of up to $100million over 10 years should thecollaboration be extended through that timeframe Gilead will have the first option tolicense Yale inventions that result from thecollaboration

What can be done to improve theclimate for clinical trials in the UnitedStates I recently coauthored a paper for anInstitute of Medicine report on clinical trials(18) We concluded that as the UnitedStates is reconfiguring the delivery ofmedical care under healthcare reform wehave an opportunity to include ldquoclinicalresearchrdquo in the business plan of new

entities such as accountable careorganizations A small tax on healthcare-related revenues could help support thisresearch In addition it is critical formedical students and trainees to beeducated in the importance and conduct ofclinical research

The leadership of the ATS has beenquite explicit in endorsing the views oncollaboration between industry andacademia espoused by the AmericanCongress and the NIH The Past-Presidentof the ATS Dr Nicholas Hill and hiscolleagues have stated ldquosuccessfulcollaborative efforts across academiagovernment and industry benefit usdaily We believe it is important for theATS to rededicate itself to fosteringa scientific culture that valuesinclusivenessmdasha scientific community ofexcellencerdquo (19) We encourage otherprofessional societies to adopt policiessimilar to that of the ATS

New Opportunitiesfor Collaboration

There are many opportunities for industryndashacademia collaborations in areas that areprecompetitive (genomics biomarkers

Figure 7 Recently formalized academiandashindustry partnerships BMS = Bristol-Myers Squibb Calibr = California Institute for Biomedical Research disc =discovery DTMI = Duke Translational Medical Institute GSK = GlaxoSmithKline JV = joint venture M = million POC = proof of concept RampD = researchand development UCB = University of California Berkeley UCSF = University of California San Francisco Wash Univ = Washington University in StLouis (Provided by and used with permission of Dr Robert M Califf Duke University Medical Center)

Special Article 37

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

resources like genetically altered micechemical libraries and cutting-edgeimaging methods

For example a new model that Merckhas just initiated is the California Institutefor Biomedical Research (Calibr) Calibr isan independent not-for-profit organizationstartedMarch 2012 in San Diego CaliforniaMerck has made a $92 million commitmentto Calibr over the next 7 years Calibr willprovide academic collaborators with a rangeof industry infrastructure support such ascompound screening and medicinalchemistry Any investigator in any countryin the world can approach Calibr If theirproject or lead or target is accepted Calibrwill collaborate to bring the concept to proofof principle Proof of principle will triggera decision by Merck to become a formalcollaborator or to decline interest and returnto the academic institution and Calibr therights to the potential product

Another example is Pfizerrsquos Centers forTherapeutic Innovation (CTI) located inBoston New York City San Francisco andSan Diego and focused on the developmentof biologic therapies CTI research staffincludes both Pfizer employees andacademic scientists in some casescolocated in the same facility In additionto financial resources CTI provides

investigators access to select Pfizercompound libraries proprietary screeningmethods and antibody developmenttechnologies CTI will enable academiccareer advancement through research andpublication while creating significantfinancial opportunities through milestonesand royalties

In yet another collaboration thisbetween Gilead Sciences and Yale School ofMedicine scientists from both organizationswill work together to identify novel cancertherapies Gilead is providing $40 million inresearch support and basic scienceinfrastructure development during theinitial 4-year period of the collaborationGilead will provide a total of up to $100million over 10 years should thecollaboration be extended through that timeframe Gilead will have the first option tolicense Yale inventions that result from thecollaboration

What can be done to improve theclimate for clinical trials in the UnitedStates I recently coauthored a paper for anInstitute of Medicine report on clinical trials(18) We concluded that as the UnitedStates is reconfiguring the delivery ofmedical care under healthcare reform wehave an opportunity to include ldquoclinicalresearchrdquo in the business plan of new

entities such as accountable careorganizations A small tax on healthcare-related revenues could help support thisresearch In addition it is critical formedical students and trainees to beeducated in the importance and conduct ofclinical research

The leadership of the ATS has beenquite explicit in endorsing the views oncollaboration between industry andacademia espoused by the AmericanCongress and the NIH The Past-Presidentof the ATS Dr Nicholas Hill and hiscolleagues have stated ldquosuccessfulcollaborative efforts across academiagovernment and industry benefit usdaily We believe it is important for theATS to rededicate itself to fosteringa scientific culture that valuesinclusivenessmdasha scientific community ofexcellencerdquo (19) We encourage otherprofessional societies to adopt policiessimilar to that of the ATS

New Opportunitiesfor Collaboration

There are many opportunities for industryndashacademia collaborations in areas that areprecompetitive (genomics biomarkers

Figure 7 Recently formalized academiandashindustry partnerships BMS = Bristol-Myers Squibb Calibr = California Institute for Biomedical Research disc =discovery DTMI = Duke Translational Medical Institute GSK = GlaxoSmithKline JV = joint venture M = million POC = proof of concept RampD = researchand development UCB = University of California Berkeley UCSF = University of California San Francisco Wash Univ = Washington University in StLouis (Provided by and used with permission of Dr Robert M Califf Duke University Medical Center)

Special Article 37

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE

animal models) in using the ldquobigrdquodatabases that healthcare systems haveand in the arena of diseases of thedeveloping world Collaboration will spurinnovation in the development of newmedicines and vaccines and in healthcaredelivery Merck regards itself as a globalcompany yet our products reach only 20of the worldrsquos population No single sectorworking alone can bring the neededmedicines vaccines delivery of care andinfrastructure to prevent and treat diseasesin the remaining 80 of the worldrsquospopulation collaboration betweenacademia and the pharmaceutical industryis absolutely necessary

In education we also see opportunitiesfor new kinds of collaboration Merck hascreated courses in drug discovery anddevelopment because most doctors have noidea how the medications they prescribewere created or what stands behind thesemedicines in terms of efficacy and safetydata or evaluation by health authoritiesA new opportunity in education will be tocreate training programs in regulatoryscience

Francis Peabody said ldquoThe secret inthe care of the patient is caring for thepatientrdquo (20) I think the secret of a truepartnership is acting like you have a truepartner This applies to both academia and

industry We need to partner for the sake ofmodern medicine we need to do it for thesciences fundamental to medicine andmost of all we need to do it for ourpatients n

Author disclosures are available with the textof this article at wwwatsjournalsorg

Acknowledgment This paper reflects both thesubstance and detail of the Presidentrsquos Lectureoriginally delivered on May 22 2012 It has beenmodified slightly to include revisions requestedby the editor and to accommodate the articleformat of a journal The author thanks Edward AOrsquoNeill PhD for editorial assistance SharonOrsquoBrien for figure preparation and Kristen Lewisfor assistance with manuscript submission

References

1 The Nobel Prize in Physiology or Medicine 1950 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1950

2 Lewis Hastings Sarett December 22 1917ndashNovember 29 1999 TheNational Academies Press (httpwww nap edureadingroombooksbiomemslsarett htm) 2012 [accessed 2012 Jul 19] Available fromhttpwwwnapedureadingroombooksbiomemslsaretthtml

3 The Nobel Prize in Physiology or Medicine 1952 Nobelprizeorg[accessed 2012 Jul 19] Available from httpwwwnobelprizeorgnobel_prizesmedicinelaureates1952

4 Hart PD A change in scientific approach from alternation to randomisedallocation in clinical trials in the 1940s BMJ 1999319572ndash573

5 Isaacson W Steve Jobs New York NY Simon amp Schuster 20116 Paul SM Mytelka DS Dunwiddie CT Persinger CC Munos BH

Lindborg SR Schacht AL How to improve RampD productivity thepharmaceutical industryrsquos grand challenge Nat Rev Drug Discov20109203ndash214

7 2011 Merck Form 10-K Merck amp Co Inc 2012 Feb [accessed 2012 Jul26] Available from httpwwwmerckcominvestorsfinancialsannual-reportshomehtml

8 Apple Inc Form 10-K Apple Inc 2011 Oct [accessed 2012 Jul 26]Available from httpfilesshareholdercomdownloadsAAPL1990832756x0xS1193125-11-282113320193filingpdf

9 Dorsey ER de Roulet J Thompson JP Reminick JI Thai A White-StellatoZ Beck CA George BP Moses H III Funding of US BiomedicalResearch 2003ndash2008 JAMA 2010303137ndash143

10 Moses H III Dorsey ER Matheson DH Thier SO Financial anatomy ofbiomedical research JAMA 20052941333ndash1342

11 ResearchAmerica America Speaks Poll Data Summary Volume 52004 Available from httpwwwresearchamericaorguploadsAmericaSpeaksV5pdf

12 Jasny BR Chin G Chong L Vignieri S Again and again and againData replication and reproducibility Science 20113341225

13 Naik G Scientistsrsquo Elusive Goal Reproducing Study Results Wall StreetJournal 2011 Dec [accessed 2012 Aug 5] Available from httponlinewsjcomarticleSB10001424052970203764804577059841672541590html

14 Prinz F Schlange T Asadullah K Believe it or not how much can werely on published data on potential drug targets Nat Rev DrugDiscov 201110712

15 Begley CG Ellis LM Drug development raise standards for preclinicalcancer research Nature 2012483531ndash533

16 Reliability of lsquonew drug targetrsquo claims called into question Naturecom2011 Sep [accessed 2012 Jul 27] Available from httpblogsnaturecomnews201109reliability_of_new_drug_targethtml

17 A new pathway for the regulation and governance of health researchThe Academy of Medical Sciences 2012 Jan [accessed 2012 Jul 26]Available from httpwwwacmedsciacukindexphppid=99amppuid=209

18 Califf RM Filerman GL Murray RK Rosenblatt M The Clinical TrialsEnterprise in the United States A Call for Disruptive InnovationInstitute of Medicine 2012 Apr [accessed 2012 Jul 25] Availablefrom httpwwwiomeduzmediaFilesPerspectives-Files2012Discussion-PapersDrug20Forum-Call20for20CTEpdf

19 Reiss TF Moss J Osborne M Curtis JR Hill NS Collaborativescience and the American Thoracic Society cooperation in harmonywith conflict of interest Am J Respir Crit Care Med 2012185347ndash349

20 Peabody FW The care of the patient JAMA 192788877ndash88221 Pharmaceutical Research and Manufacturers of America Drug

discovery and development understanding the RampD process[accessed 2012 Jul 26] Available from httpwwwInovationorg

22 Roger VL Go AS Lloyd-Jones DM Adams RJ Berry JD Brown TMCarnethon MR Dai S de Simone G Ford ES et al American HeartAssociation Statistics Committee and Stroke Statistics SubcommitteeHeart disease and stroke statistics 2011 update Circulation 2011123e8ndashe209

23 Department of Health and Human Services Centers for DiseaseControl and Prevention HIV mortality (through 2008) [accessed 2012Jul 26] Available from httpwwwcdcgovhivtopicssurveillanceresourcesslidesmortalityindexhtml

24 Credit Suisse F-D-C Reports Inc and Windhover Information IncAdapted with permission from IN VIVO The Business and MedicineReport Elsevier 2009

25 Munos B Lessons from 60 years of pharmaceutical innovation NatureReviews Drug Discovery 20088959ndash968

38 AnnalsATS Volume 10 Number 1| February 2013

SPECIAL ARTICLE