thank you for joining ismpp u today! · speakers for today • martha r. matteo, phd –academic...

Thank you for joiningISMPP U today!

Today’s program will begin promptly at12:00 noon EST

For optimal viewing, please utilizethe ‘Full Screen’ button at the

top left of your screen

Michele

Stamp

New Realities for Drug/DeviceDevelopment and Commercialization

Intelligence in Publication Strategy WebinarJune 18, 2008

Speakers for today

• Martha Matteo, PhD• Wayne Rosenkrans, PhD• Both:

– scientists with long history in pharma R&D andCompetitive Intelligence (CI)

– active in SCIP: BOD and Presidency– bring the CI perspective to this issue:

• what’s happening in the external environment?• what are the trends, possible disruptors, and alternate

futures?• fit with our Mission and Vision?• how do we assess our risk, prepare ISMPP members?

Speakers for today

• Martha R. Matteo, PhD– academic and industrial research and teaching– founded CTI function at global pharma company– active in academic/industry consortium (NYAS)– author, speaker on C(T)I

• Wayne Rosenkrans, PhD– strategic planning for both R&D and commercial pharma,

KM for CI initiatives– industry-relevant publishing– collaboration with care delivery systems for new

approaches to “Learning Healthcare Systems”– chair of the “Personalized Medicine Coalition” (gov’t,

providers, biopharma, Dx, insurers) and DistinguishedFellow, MIT

Role of ISMPP- Vision

to be the recognized and respectedauthority for the pharmaceutical,

biotech, and device industries medicalpublication profession.

Role of ISMPP- Mission

• Support medical publicationprofessionals: education/advocacy.

• Promote integrity and excellence:author and contributor transparency,open exchange of data.

• Be at the forefront of informationsharing and debate of medicalpublication issues ….

Today’s realities suggest issues for ISMPPto consider:

• Transparency: Actual authors?

• Bias: Trial design, reporting?

• Timeliness: Side-effect reports?

• Resulting public reaction: Hostile

… with implications for all players

• Rx and Dx companies: modification of trial design

and reporting?• FDA: post-market surveillance??• Journal publishers:

no change?reactive?proactive?

Goals for today

• Consider current situation in Rx/Dx relatedpublishing and challenges we face

• Consider trends, disruptors, and alternativefutures which could dramatically affect thecurrent business model

• Should / how can ISMPP prepare itsmembership for success in the short andlonger term?

• Next steps??

Dr. Rosenkrans will prepare usto discuss three scenarios:

• “Hard crank turning”…• “Revenge of Joe Public”…• “Brave new world”…

Dr. Wayne Rosenkrans:

“What about the future?”

• What is happening in the environment today tocreate very different realities for tomorrow?

• How will it impact ISMPP-relevant businessenvironment?

Re-evaluating the basic valueproposition…

Value in health care is often expressed asthe increment in clinical benefit achieved(health and/or quality of life improvement),for those receiving a particular service orset of services, in conjunction with theinvestment required.

…generates a new refrain inhealthcare

Pay for What Works

Eliciting a new series ofquestions

What works best? …for whom?

…under what circumstances?

That can be interpreted as

• What works best – comparative clinicaleffectiveness

• …for whom – personalized healthcare• …under what circumstances – real

world effectiveness

Its all about Evidence…

Identifying compelling needs

We need a learning healthcare system...

• A system in which evidence emergesas a natural by-product of the caredelivered

Identifying compelling needs

We need to start now to develop...

• Substantially enhanced capacity fordevelopment of evidence and guidance forclinical decision making

• Stronger incentives and tools for theapplication of proven services

• Effective communication for and betweenpatients and providers about the nature ofevidence and what it suggests

For product developers• New thinking is required

– The old hurdles…• Efficacy• Safety• Production assurance

…are no longer sufficient

– Three new hurdles must be cleared as well…• Effectiveness• Coverage• Reimbursement

…looking beyond market approval toward greaterembedment in clinical practice and attendantcommercial success.

…its all about evidence

• Innovation itself is no longer sufficient• The value of the innovation must be

proven:– In the clinic– With real patients– And real providers– In a cost effective way to demonstrate

• What works best• For whom• Under what circumstances

The generation of evidence…

Confirming real-world, comparative clinicaleffectiveness must be:• Core element of clinical development plans• Considered with input from the FDA and other entities, i.e.,

- Center for Medicare Services (CMS),- Agency for Healthcare Research in Quality (AHRQ)- Health Technology Assessment (HTA) at private payers.


• Generating meaningful segmentationof patient populations, by whatevertechnology is appropriate (genomic,imaging, informatic), in order toincrease the benefit of therapy –

Personalized Healthcare


Offers a unique opportunity to demonstrate:

What works bestFor whom

Under what circumstances

But traditional drug developmentwon’t get us there…

Traditional Development

Phase I Phase II

1 2 3 4 5 6 7 8 9 10 11 12

Phase III App Phase IV

Revenue with rapid and significantincrease in patient exposure

(17 mo) (30 mo) (27 mo) (11 mo)

(8y2m)

Duration based on 2001-2003 Industry Median (CMR)

Without breaking the bankAverage R&D costs per NCE drug launched

0

200

400

600

800

1000

1200

1400

1600

Year

$M (

in y

ear

2000

dol

lars

)

2000

80295Post-launch

costs

2003

1400R&D Heads@ IBC mtg

2003

1700Bain & CoDec 03

Historical data from DiMasi, Tufts Center for Drug Development

2010

2000Limited Comparative Effectiveness

2300Extensive Comparative Effectiveness

A new development paradigm isneeded

Therapydefined,

rolling NDA,disease

biomarkerdevel.

Trialsdesigned

withpayers &regulators

Simulation–based

trialdesign

Adaptivepivotalstudies

Surrogateendpointsdelineatebenefit/

risk

IR – Initial Release FR – Full ReleaseBefore duration based on 2001-2003 Industry Median (CMR)

Future Development

FIM - POP POP –> Release Outcomes

Earlier revenue with more gradual increase inpatient exposure

(30 mo) (42 mo)

IR

(3 mo)(5y2m)

1 2 3 4 5 6 7 8 9 10 11 12

FR

Outcomes confirm surrogate hypothesis; reimbursementconfirmed; safety profile acceptable; alternative

evidence generation, continuous learning

Continuous Data Acquisition

“Development Never Stops”

Case Study – Informatic PHC

Can a large and fully integratedCan a large and fully integratedElectronic Health Record System (EHR)Electronic Health Record System (EHR)be used to demonstrate the value ofbe used to demonstrate the value ofantidiabeticantidiabetic therapy, in terms of therapy, in terms ofcomparative benefit and risk, in ancomparative benefit and risk, in anenvironment reflecting actual clinical useenvironment reflecting actual clinical useof the therapy?of the therapy?

Anil Jain, MD Copyright 2007, Cleveland Clinic

Clinical DataRepository

CCF-AZ DMData Set

Creating the Data Set…

CCF-AZDM

Definitions

SocialSecurity

Death Index

• CCF has utilized anEHR since 2000.

• EHR Tethered PHR• ePrescribing• Large Clinical Data

Repository– 3.5 million patients– 5 million

prescriptions– 89 million laboratory

results• Scope of Data

– Medications– Demographics– Diagnoses– Procedures– Laboratory– Imaging

•• CCF has utilized anCCF has utilized anEHR since 2000.EHR since 2000.

•• EHR Tethered PHREHR Tethered PHR•• ePrescribingePrescribing•• Large Clinical DataLarge Clinical Data

RepositoryRepository–– 3.5 million patients3.5 million patients–– 5 million5 million

prescriptionsprescriptions–– 89 million laboratory89 million laboratory

resultsresults•• Scope of DataScope of Data

–– MedicationsMedications–– DemographicsDemographics–– DiagnosesDiagnoses–– ProceduresProcedures–– LaboratoryLaboratory–– ImagingImaging

Abbreviation Class Examples

“Big” biguanides Glucophage(metformin)

“TZD” thiazolidinediones Avandia(rosiglitazone)

“SFU” sulfonylureas Glucotrol (glipizide)

Dphen & MegD-phenylalaninederivatives. AKA.Meglitinides

Starlix (nateglinide)

“AGI”Alpha-glucosidaseInhibitors

Precose (acarbose)

Medication Classes

Cohort

• >18 years old• Diagnosis of Diabetes in EHR.• Prescribed single oral hypoglycemic Agent.

– Patients with the metabolic syndrome andpolycystic ovarian syndrome excluded

– Patients on AGI excluded (n=146)

• Baseline = Earliest Date of HypoglycemicRX in a diabetic patient.

• Pts without follow-up were censored for alloutcomes except mortality.

Predictors

• Measurements: Lipids, BMI, BP, LVEF,Hba1c, eGFR, LFTs, Alb:Cr

• Medical History: CHF, Liver Disease, KidneyDisease, CAD, Stroke/TIA, Hepatitis B/C,Atrial Fibrillation, New Diabetic?

• Demographics: Age, Gender, Race• Oral Hypoglycemic Medication Class:• Meds: ACE / ARB, Cholesterol, ASA, Plavix

Outcomes

• Nephropathy• Renal Insufficiency• Mortality• Coronary Artery Disease• Stroke/TIA• Liver Injury• Heart Failure• Continuous Outcomes: BMI, Hba1c, LDL,

HDL, TG.

Statistical Methods

• Fit Cox and OrdinaryLeast Squaresmodels

• Created nomogramsfrom models

• Calculator createdusing modelcoefficients.

• Models validatedusing random sub-sample

Learning Decision Support

Conclusions

• Models are very good at predicting clinicaloutcomes

• Models for predicting continuous outcomesare better than simply relying on baselinealone.

• Successful use of the EHR to predictoutcomes in type II diabetes

• Interactions allow for tailored treatmentbeyond AHRQ recommendations.

• Potential to extend these techniques to otherdiseases.

Next Steps for Pharma

• Acknowledge a new environment isemerging

• Rethink the old models– Research– Development– Commercialization

• Embrace the need for new business models

… or just keep turning the crank harder

What are the strategic implicationsinherent in the future ISMPP must

contemplate?

Worlds for ISMPP to consider:Scenario 1: Hard Crank Turning

• Companies set trial/label strategiesconsistent with intended label, incollaboration with the FDA.

• Companies decide what/where/when topublish

• Journals accept papers, subject to peerreview

• Reimbursers rely largely on published, peer-reviewed data for systematic review

Issues for ISMPP to consider:Scenario 2: Revenge of Joe Public

• In a continuing anti-pharma climate, HHSagencies demand “real-world comparativeeffectiveness” based upon “untainted” data

• Companies are advised that moretransparent trials, powered for comparativeassessment, will positively impactcompany’s reputation and help the industryas well– concerns about increased risk and cost– possible greater risk if eroding public

perception leads to less desirable policy


Publishers raise hurdles (à la oncology)– Publishers assert influence over

quality/transparency of what they accept; institutetougher disclosure rules (authorship, conflict-of-interest, bias issues)

– Publishers demand comparative trials, whereappropriate; find peer reviewers who canevaluate whether trials are properly powered tojustify claims


Will it work?• Can ISMPP members as a group have an

influence?• Will companies push back? Will it matter if

they do?• Will other means of sharing data emerge

that dramatically change role of ISMPPmembers?

Issues for ISMPP to consider:Scenario 3: Brave New World

Loss of data control by pharma to otherentities?

• Will FDA/NIH, partnered with professionalassociations/academia, expand internalcapacity and effectively remove pharma assponsors for market approval trials?



• Will a new quasi-governmental agencypartnered with AHRQ, CMS, associations, andacademia conduct all primary research incomparative clinical effectiveness?

• Cost effectiveness?



• Could a move toward a “Super Sentinel”learning healthcare system totally eliminate theRCT as we know it today in favor of adaptivetrials and modeling?



• How would pharma adapt? Could pharma stillsponsor studies for market approval, but othersgenerate data for reimbursement?

… and who pays for all this anyway?


• Will there still be trials as we knowthem?

• Will results be published as discreteentities? Through what channels?

• What will reimbursement reform looklike?

Future strategic implicationsfor ISMPP to consider:

• Are the three scenarios all endpoints ofchange, or are they sequential states - dowe have to pass through 2 to get to 3?

• What is the likely trajectory and timing?• Is one more/less desirable than another

(think broadly)?• What are the indicators of change and how

will ISMPP monitor them?• What changes have to occur to move the

players forward into a desirable state, andcan ISMPP help to create those changes?

Dr. Martha R. Matteo, PhD

How can ISMPP help its members torecognize and prepare for change?

Questions to consider

• Considering ISMPP Vision andMission:– Can ISMPP help assure favorable future

for its members?– Assuming change, should ISMPP

influence the evolutionary process?– If so, how do we track and anticipate

these changes for ISMPP consideration?

CI Process

• Capture, define external trends• Define possible scenarios• Identify likely “indicators” of each scenario• Monitor the indicators and possible points of

influence (ongoing):– networking– literature– collaborations

• Analyze (periodically) and recommend

CI Process:ISMPP

• Internal sponsor– Executive Committee?

• Trend analysis, indicators, scenarios– research committee? consultant?

• Monitor the indicators and possible points ofinfluence (ongoing):– entire membership

• Analyze , recommend, educate– policy, executive and education

committee??

CI Process

• What networks should ISMPP and itsmembers join, to learn and contributeamong all the players…?

• Who specifically will coordinate theeffort of “environmental scanning andanalysis.”

• How will new strategies be formulated,approved, implemented and assessed?

Q&A Discussion

Thank-you

Wayne A. Rosenkrans, Jr., Ph.D.Chairman & President, Personalized Medicine Coalition

Distinguished Fellow, MIT Center for Biomedical InnovationSciTech Strategies

[email protected]

Martha R. Matteo, Ph.D.Board Member and 2007 President

Society of Competitive Intelligence ProfessionalsDirector, KM and R&D Planning

Boehringer Ingelheim Pharmaceuticals, Inc. (ret)[email protected]

Next ISMPP U

• Topic: Gap Analysis • Date: July 16

• Time: 12 Noon EST

Thank you for joiningISMPP U today!

Your feedback is important….

Before logging off, please fill outthe brief evaluation that will appear

on your screen as you exit

thank you for joining ismpp u today! · speakers for today • martha r. matteo, phd –academic...

Documents