Companies Seek Expanded Access to Genetic Specimens



PHILADELPHIA – Drug companies want better access to study participants’ genes.

Pharmacogenomic analyses have become a key part of state-of-the-art drug trials, to better hunt down the causes of adverse events or poor drug responses, but the pharmaceutical companies funding and organizing those trials have often been stymied in collecting and using genetic specimens from study participants.

Amelia Wall Warner

The problem has grown so acute that in September a core group of research facilitators from drug companies together with representatives from academia and regulatory agencies met for a 2-day workshop so that these barriers in the United States, Europe, Japan, and the rest of the world could be better understood and participants could brainstorm solutions.

"Clinical trial sample collection for future research is vital. It provides resources to answer regulatory questions on safety and efficacy, perform testing to elucidate unexpected clinical responses during trials, and allows pharmacovigilence testing of marketed compounds. High [specimen] collection rates that are representative of clinical trial populations and informed consent for broad sample use is essential to insure that the [trial] results broadly apply to all people in the study population," said Amelia Wall Warner, Pharm.D., head of clinical pharmacogenomics and clinical specimen management at Merck in North Wales, Pa., and chairwoman of the meeting.

Despite this, trial organizers at Merck and many other companies have encountered resistance or restrictions on specimen collection and use from regulatory authorities, academic institutions, and the institutional review boards (IRBs) and ethics committees that oversee trials.

The problem may be resolving in the United States through recent actions of the Food and Drug Administration.

"There is a fine line between ethics committees that protect their populations but prevent us from fully investigating the safety and efficacy of a drug in a population," Dr. Warner said. "Health authorities will allow collections, but narrow the scope of their use. Regulatory authorities often require adequate representation of their country’s population for a drug’s approval, but because of genetic variations across populations, the sample size must be representative. Adequate statistical power is needed, but collection of optimal DNA samples for a high percent of patients enrolled in industry clinical trials is still a challenge.

"We use specimens to investigate adverse events and nonresponders, which ultimately benefits patients. Distrust is what we have to overcome. But it’s not patients who [generally] don’t want to participate, it’s the investigators," she said in an interview. "Many patients agree to participate" with specimen collection once a trial receives approval and patients understand the goals of the trial and the reasons for specimen collection, she noted.

Although workshop attendees came up with a list of ways to try to resolve the problem and acknowledged that in an era of global trials solutions need tailoring to the diverse range of barriers that often differ from country to country, the solutions largely boil down to two main strategies – better education and trust building – participants said repeatedly during the sessions.

The problem may also already be resolving in the United States through recent actions of the Food and Drug Administration, a development that may have global impact if regulatory bodies and IRBs in other countries follow the U.S. lead. Last February, the FDA issued draft guidance on clinical pharmacogenomics in clinical studies.

The draft guidance "is very supportive" of DNA specimen collection and analysis, said Gilbert J. Burckart, Pharm.D., associate director for regulatory policy in the Office of Clinical Pharmacology, Center for Drug Evaluation and Research at the FDA. "Sample collection is critical to what you do," he told the industry representatives at the workshop. "You don’t have the science unless you do it, and do it properly." He noted that work on the guidance began in 2008, with the finalized version of the guidance due out soon. The FDA received more than 200 comments on the draft, with the comment period now closed.

The draft says that pharmacogenomic information collected during both drug development and postmarketing studies "can improve the effectiveness and safety of drugs." The draft also notes that "an important prerequisite to successful use of genetic information in drug development is the appropriate collection and storage of DNA samples from all clinical trials ... Plans for general DNA sample collection should be prespecified ... even if these samples are studied only at a later time, during, or after the study. It then becomes possible to seek explanations for differences in exposure, efficacy, tolerability, or safety not anticipated prior to beginning the study."

The draft also cites three recent, real world examples where pharmacogenomic data proved critical in understanding and refining treatment challenges with certain drugs:

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