a cure for clinical trials

A cure for clinical trials

esting new drugs is a costly and frustrating headache for pharma-ceuticals companies—and the pain is about to get worse. Clinical trials

are at best difficult to manage and dogged by delays, and now the genomicsrevolution and stricter regulatory standards are compounding the problems.For pharma companies, managing the newly increased demands of clinicaltrials may become the greatest obstacle to realizing the full benefit of thenew health technologies.

Janice Cruz Rowe, Martin E. Elling, Judith G. Hazlewood, and Randa Zakhary

US pharma companies often miss their deadlines when testing new drugs.The use of marketing techniques to manage the recruitment of patients for

clinical trials could speed things up considerably.

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Not surprisingly, it is the clinical aspects of these trials that pharma compa-nies concentrate on: making sure that the research methodology or protocolleads to results capable of standing up to the scrutiny of authorities such asthe US Food and Drug Administration (FDA). But another crucial element—the recruitment of patients—is often overlooked, causing expensive delaysthat can drain much of the sales potential from any new drug. More thanhalf of all US clinical trials from 1993 to 1998 missed their deadlines by atleast a month (Exhibit 1, on the next page). A failure to get enough patientsin time accounts for 85 to 95 percent of all days lost during clinical trials(Exhibit 2, on the next spread).

The fresh opportunities unleashed in the year 2000, when the humangenome was finally charted, are set to increase the demand for patients inclinical trials. Drug research focuses on discovering novel targets: the bio-logical mechanisms, usually receptors or enzymes in human cells, throughwhich drugs work. By mapping the genome, scientists have increased thenumber of potential targets—to as many as 10,000, from about 500—andthe R&D costs associated with developing new drugs could double.1 As

1See Richard C. Edmunds III, Philip C. Ma, and Craig P. Tanio, “Splicing a cost squeeze into thegenomics revolution,” The McKinsey Quarterly, 2001 Number 2, pp. 15–9.

REBECCA REUGGER

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more new drug targets enter theR&D pipeline, poor recruitmentcould become a bottleneck, hamper-ing a company’s ability to bring newdrugs to market expeditiously.

Delays can cost pharma companiesat least $800,000 a day in lost salesfor a niche medication, such asAmaryl, an oral antidiabetic treat-ment, and as much as $5.4 millionfor a blockbuster like Prilosec, agastrointestinal medication. If someof this revenue is merely deferred, it

may be recouped once a drug goes on the market, but millions of dollars inrevenue can vanish if a competitor catches up or, worse, gains the advantagewith an earlier debut. Delays can also affect a company’s valuation, sinceinvestors closely watch the progress of new drugs: efficient clinical trials putthem on the market more quickly, so they take market share more quickly.Pharma companies may also gain a strategic edge by setting a new standardfor treating a disease, and speed to market gives physicians and patients abroader, and potentially lifesaving, choice of treatments in less time.

Finding people for trials is always hard: too many patients don’t realize theycan participate. Further, deaths and questionable practices in isolated trialshave made potential participants wary. Moreover, designers of clinical trialsare now seeking more narrowly defined sets of patients, in part to distin-guish new drugs from rivals on the market. But the most important problemis regulatory change: over the past decade, the number of patients needed foreach FDA approval has almost doubled.2

The pharma industry could therefore create enormous value by more effi-ciently recruiting participants in clinical trials. Taking a single month off a trial by improving recruitment could generate an additional $40 million in sales for an average drug. But to do so, pharma companies must radicallyalter their R&D efforts by improving the speed and efficiency of recruit-ment, and this in turn will streamline the whole clinical-trials process.

Thinking like marketers

To get patients into trials more efficiently, pharma companies must begin tothink like marketers. By setting a target for the number of patients needed in

136 THE McKINSEY QUARTERLY 2002 NUMBER 2

E X H I B I T 1

Missed deadlines

11998 survey of 163 Phase III trials, which confirm efficacy, dosage regime,and safety profile of drug.

Source: CenterWatch

Percent (100% = 163 trials1)

Ahead of schedule

On schedule

<1-monthdelay1- to 6-month

delay

>6-monthdelay

8

14

44

12

22

2Because of the size of the US market, FDA approval is a crucial step for any new drug. Although theFDA doesn’t require that testing be conducted in the United States, most pharma companies willcomplete at least some tests there to make approval easier.


a trial, the R&D team in essence creates a sales challenge: to get enoughpatients to buy the “product”—in this case, participation in the trial. To dothat job, companies will have to borrow a few marketing techniques.

Planning for a clinical trial begins with the design of a protocol, which setsout the criteria for patients who can be admitted to the trial, maps the treat-ment they will receive, and establishes how they will be monitored. In addi-tion, the protocol includes such administrative details as the handling ofpatient consent and the marketing of the trial. Sites and physicians for thetrial are then chosen. Physicians are offered incentives—not only paymentfor their own time and other expenses but also free equipment, all-expense-paid trips to conferences, and invitations to speak at prestigious events.Physicians and nurses at each certified site get extensive training in theprotocol used to administer the trial and in reporting its results properly.

Typically, the final and most crucial phases in the development of a druglast at least four months and involve 3,000 patients, though the number can vary depending on the disease or ailment targeted. Earlier phases, whilealso time-consuming, involve fewer patients. Commonly, for every patientenrolled, four to ten must be screened to determine their eligibility. Pharmacompanies must also plan for unforeseen events to ensure that recruitment issuccessful even if they occur.

The recruitment of patients for trials generally follows two paths simultane-ously: participating physicians recruit suitable people from their own patient

137A C U R E F O R C L I N I C A L T R I A L S

Percent

1Joint 2001 McKinsey and Lehman Brothers survey of 49 executives and chief risk officers of pharmaceuticals, biotech, and medical-device companies.

2Validation of patients’ data on forms submitted by physicians.Source: CenterWatch; Parexel Pharmaceutical International Sourcebook, 2000; Lehman Brothers; interviews; McKinsey analysis

Difficulty inrecruiting patients

100% = 49 executives and chief risk officers1

Difficulty in recruiting patients is the mostfrequently cited cause for delay in clinical trials . . .

Resolution ofdata discrepancies

Collection of case-report-form data

Source-documentverification2

Institutional-review-board approval

2719

13

23

18

100% = 53 days

Other

. . . and the largest contributor to days lost

85–95 5–15

E X H I B I T 2

The lost days


lists while pharma companies advertise directly to patients and then passprescreened lists of candidates on to the physicians.3 The efficiency of bothapproaches to recruitment can be improved.

Segmenting the physicians

Many companies use a one-size-fits-all approach to recruiting and managingthe physicians who participate in clinical trials. But just as some salespeopleare better at bringing in customers, some physicians are better at bringing inpatients for clinical trials. Although many companies recognize this truth,few have tried to identify and manage the top performers systematically.

The first step for pharma companies is to segment physicians on the basis ofhow well their pools of patients fit the protocol required by a clinical trialand their success in meeting recruitment targets in earlier ones. A physicianwhose practice includes a high proportion of targeted patients (people withdiabetes, say) could get an above-average recruitment target, greater support,and more attractive incentives. One top US pharma company, for example,discovered that some physicians with superb access to target patients wereshort of staff to manage the protocols for clinical trials. Providing a part-time nurse to help screen patients increased the rate at which these physi-cians recruited patients. Another North American clinical trial enrolled2,000 recruits in 16 weeks—an exceptional pace—because the companyfocused on its high performers, who had access to the right patients.

Besides segmenting physicians by the number of patients they screen andenroll in a given week and by the number of weeks they take to meet theirenrollment targets, pharma companies must track the percentage of patientswho pass the initial screenings and complete the trial, for this informationpermits those companies to develop accurate databases of physicians whohave good access to patients, the necessary infrastructure, and the commit-ment to ensure that enough patients go on to the finish line (Exhibit 3).Starting from scratch, it could take a company years to complete such adatabase. But improvements in the way companies try to find the physiciansmost likely to meet their recruitment targets are possible even before theprocess ends, largely through the steady development of deeper relationshipswith physicians who consistently deliver high numbers of patients.

Marketing to patients

In general, the efforts of pharma companies to market clinical trials arehardly sophisticated or effective. One company that was testing an arthritis


3In the United States, advertising for clinical trials is generally allowed if the message isn’t misleading.Other countries have stricter regulations, and some countries prohibit direct advertising for thispurpose, thus forcing the pharma companies to rely on the efforts of physicians.


medication, for exam-ple, gave participatingphysicians a budget forlocal advertising.Instead of buying adsaired during cable tele-vision shows viewed bythe elderly or market-ing the trial directly tothem, the physicianspurchased space ingeneral-interest localnewspapers and gotmarginal results for themoney.

Both the message andthe mass media inwhich it is disseminated must be chosen wisely if marketing money is to bewell spent. First, a pharma company must create a clear profile of the targetpatient, including age, sex, and ethnicity. Parts of this profile might beimplicit in the protocol, but a careful demographic analysis will usuallymake the profile more detailed. Once it is complete, companies need to knowhow target patients get information about clinical trials and what mightserve as an inducement to take part in them.

An example of effective marketing comes from a US company that wasresearching a drug for Type II diabetes, which disproportionately affectsHispanics. Using focus groups in Hispanic communities, the company setout to learn what would be most likely to motivate these patients to partici-pate in a trial: free medical care, access to more effective treatment, or achance to help find a cure for a disease. It found that since many patients inthe target population lacked health insurance, free medical care and medica-tion had the greatest appeal. With this marketing data in hand, the com-pany’s efforts at recruitment—and the trial—proceeded on schedule.

Indeed, segmenting the audience and targeting the groups with the highestvalue can also guide decisions about how to convey the message. Televisionspots, ads in local newspapers, and posters at bus stops, for instance, reachdifferent demographic audiences.

Anticipating problems

By quickly recognizing when recruitment is running behind schedule andpinpointing the problem, pharma companies can avoid days of delay. But


E X H I B I T 3

A checkup for physicians

Low High

Low

HighHigh potential High performance

Supportmanagement of

patients during trial

Compensate well,build long-term

relationships

Exclude Low potential

Help recruitpatients with

marketing support

Physicians’retention success

• Number of patientswho complete trials

• Number of patientsscreened or enrolledper week

• Number of weeksrequired to meettotal patient-enrollment targets

Physicians’enrollment success


first—from the beginning of the trial—the companies should develop early-warning systems and contingency plans.

Companies with successful programs for recruiting patients often overbuildfrom the start, as one company in Latin America did by qualifying moreclinics than necessary as trial sites so they could be activated immediately ifneeded. A European company produced weekly patient-enrollment reportsand monitored responses to particular ads. When problems arose, it was ableto bolster its advertising and switch to a different approach, since it hadalready bought options on media slots in markets where it feared it mightmiss its enrollment targets. In both cases, contingency plans helped thesecompanies stay on course.

Bringing marketers and scientists together

Once pharma companies recognize that marketing skills are essential forbringing enough patients into clinical trials, it becomes obvious that organi-zational changes linking marketers with R&D are needed as well. Suchchanges do not mean substituting brash commercialism for scientific stan-dards, but they do require a better understanding of what motivates peopleto participate in clinical trials.

To focus on recruitment for these trials, a few of the largest and most suc-cessful companies have recently established centers of excellence that includeemployees from clinical development, marketing, and market research. Themarketers have insights that were often missing or overlooked when thetrials were being designed: a knowledge of consumer behavior and the abil-ity to track the progress of marketing campaigns. Such centers thus helpcompanies complete their studies on schedule.

By contrast, in today’s standard approach, the manager of a clinical trial,who has overall responsibility for its success, develops the recruitmentprocedures. But these managers are evaluated on such criteria as whether the results of a trial stand up to regulatory scrutiny; the timeliness of recruit-ment plays little if any role. A manager should therefore be put directly incharge of recruitment for clinical trials, and that manager should be evalu-ated, in large part, on the ability to get sufficient numbers of patientsenrolled on time—which resembles the kind of accountability that market-ing managers bear. By retargeting a part of the recruitment manager’s incen-tive package, pharma companies can raise the level of accountability forrecruitment and counteract the tendency to regard delays as inevitable.

Involving marketers early in R&D also helps ensure that recruitment con-siderations are included from the outset in the planning for clinical trials.Ideally, the recruitment plan should be based on input from a variety of



functions. But many pharma companies, regarding it as unscientific to con-sider practicalities when they design protocols for clinical trials, don’t think,early in the planning process, about recruiting patients. Such a lack of fore-sight is the harbinger of delays and lost potential.

In one extreme example, a recent trial focusing on the treatment of braintumors needed patients who had already undergone a rare (and less effective)treatment for their condition. But so few people had gone through this treat-ment that not enough patients could be found to satisfy the criteria. Inanother case, the clinical trial for a medication that would be prescribed bygeneral practitioners called for complex screening examinations with equip-ment that most of them didn’t have. Too often, protocols tend to presupposean ideal scientific setting, and designers include tests or other proceduresmerely to cover all contingencies. A more thoughtful design, as we have seenin practice, often loosens up the requirements imposed on participatingphysicians and patients, without sacrificing any scientific credibility. In bothof the cases described above, equally rigorous trials could have been carriedout using more practical protocols.

Scientific integrity, far from being compromised, is actually enhanced whenpractical considerations such as the availability of patients and equipmentare dealt with realistically. If a highly specific protocol is necessary, pharmacompanies must be aware of the inevitable constraints. In the final phase oftrials for one diabetes medication, for instance, the protocol called for highdoses, which were regarded as essential even though only a few patientscould tolerate them. By recognizing this problem early, the company couldhave anticipated the resulting high dropout rate and recruited a larger poolof participants from the outset instead of enduring delays late in the trial.

New technologies such as biomedicine are opening up vast new horizons forthe pharma industry, but they can be reached only through meticulous clini-cal trials. To deliver value, pharma companies must conduct them safely,thoroughly, and expeditiously. These companies can offer the greatest valueto patients, physicians, and investors alike by systematically improving everyaspect of recruitment. Companies that pursue business as usual face stagger-ing losses. Those that get it right may reap huge rewards.

The authors wish to acknowledge the contributions of Teri Lawver in developing both the marketingframework described in this article and the article itself.

Janice Cruz Rowe and Randa Zakhary are consultants, Martin Elling is a principal, and JudithHazlewood is a director in McKinsey’s New Jersey office. Copyright © 2002 McKinsey &Company. All rights reserved.



a cure for clinical trials

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