Thursday, May 28, 2015

Pharma's clinical development at cross purposes with itself

Developing new products through clinical trials represents the lifeblood of branded pharmaceuticals. Unless companies can develop new products to replace the existing ones that lose patent protection, their revenues will erode as payers and patients fill prescriptions with less expensive generics. Yet despite the vital importance of managing clinical development, pharma is content to outsource its central components in the hope that costs and timing can remain within budget.

Pharma's clinical development at cross purposes with itself

Developing new products through clinical trials represents the lifeblood of branded pharmaceuticals.  Unless companies can develop new products to replace the existing ones that lose patent protection, their revenues will erode as payers and patients fill prescriptions with less expensive generics.  Yet despite the vital importance of managing clinical development, pharma is content to outsource its central components in the hope that costs and timing can remain within budget.

Contract research organizations (CROs) are the most important of the agencies on which pharmas rely for managing clinical trials.  CROs function similarly to general contractors on a building construction project in that they hire and manage the subcontractors.  Trial service suppliers represent one type of subcontractor that works on clinical trials.  Their tasks include such diverse matters as analyzing blood samples in the lab. 

The other category of subs consists of the clinics, medical practices, hospital departments and academics that recruit patients into the various trials.  CROs claim that their experience on previous trials makes them aware of which clinical sites are most likely to rapidly and reliably recruit the required number of patients for a sponsoring pharma's particular study.

Yet last week Tufts University's Center for the Study of Drug Development (CSDD) released the results of its study showing that "11% of sites in a given trial typically fail to enroll a single patient, while 37% under-enroll." 

Now CSDD is one of pharma's most favored suppliers.  For example they regularly produce reports for the industry that inflate the costs of developing each drug.  So it merits serious attention when a go-to research house for pharma produces a study showing that almost half of all trial sites abjectly fall below recruitment expectations on any given study.

When CROs retain trial sites, they expect each practice will be able to meet its recruitment quota from its own patients.  That hope remains at best a long shot because even high-recruiting sites sometimes fall far below their usual performance on particular studies.  What typically differentiates the good recruiting sites from the poor ones is the former's ability to enroll patients from referring physicians at outside practices.

Persuading outside physicians to send their patients to a clinical trial managed by another, potentially competing practice entails communication patterns that are foreign to most medical personnel.  Medicine as a profession largely uses prescriptive rather than persuasive communication -- do this, avoid that, take this medication, get these x-rays and lab tests.  For sites to perform this unfamiliar task well, while adhering to ethical guidelines, sponsors have to supply them with essential communication materials and hand-holding.  CROs rarely provide services that meet this need.  Among their clinical research associates (CRAs) that visit trial sites, many are neophytes that do little more than complete checklists related to data entry, testing and reporting.  Most experienced CRAs carry heavy workloads that prevent coaching, role playing and communication training.

The fallback response of pharma sponsors and CROs consists of retaining ad agencies and medical communication houses to produce materials for facilitating communication with prospective patients and their referring physicians.  The value of this remains quite limited, largely because high-recruiting trial sites have five to twenty-five trials running at all times.  Study coordinators with places to fill in so many studies are unlikely to use Q&A scripts and other materials from the marketing agency's package.

Retreating farther into "hail Mary" territory, pharmas then decide to just add more sites and/or provide the existing ones with money to buy radio and newspaper ads.  They all seem to feature variations on the same tagline: "Do you have the following symptoms...Then you might qualify for a study..."

These media ads also produce limited results, largely because most medical practices are not professional advertising buyers and they lack the buying power of multi-national corporations.  Medical and nursing schools do not teach which media, copy and graphics create the most effective appeals for which conditions.  Large, corporatized providers such as Penn, Jefferson/Main Line and other, integrated networks maintain professional advertising departments, but not many other practices do.  Besides, the value of media advertising for creating trial awareness among appropriate candidates remains open to question.

So while effectively managing clinical trials is a crucial function for pharma and represents its second-largest source of expenditures after marketing, the industry has historically thrown money at it indiscriminately instead of closely analyzing matters in the way it looks at medical conditions.

Whether pharma is designing a new study or trying to renovate one where patient recruitment has stalled, the industry would do better by adopting an axiom from the practice of medicine which it tries to serve − first diagnose, then treat.  When new projects are at the planning stage, adopting this medical axiom would involve looking at what is required to recruit patients for each study in a timely, cost-effective manner.  Once a study is in the clinic, if patient recruitment starts to move more slowly than what was budgeted, the most efficient recourse consists of determining why it is lagging and then using the results to implement effective steps short of expensive, time-consuming, protocol amendments.

Pharma maintains precedents within its own history and operations for effectively addressing its most important function.  Whether it will do so remains open to question because all operations these days fall under the short-term, penny-wise-and-pound-foolish dictates of finance.  But the right road is at hand and it just remains for strong R&D managers to reassert control over their industry.

President, Pharmaceutical Business Research Associates
About this blog

Check Up covers regional health news and a wide array of healthcare topics from pharmaceutical happenings to patient safety. Read about some of our bloggers here.

Portions of this blog may also be found in the Inquirer's Sunday Health Section.

Michael R. Cohen, R.Ph. President, Institute for Safe Medication Practices
Daniel R. Hoffman, Ph.D. President, Pharmaceutical Business Research Associates
Hooman Noorchashm, M.D., Ph.D. Cardiothoracic surgeon in the Philadelphia area
Amy J. Reed, M.D., Ph.D. Anesthesiologist and Surgical Intensivist in the Philadelphia Area
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