A Review Of The 2011 Post-Approval Summit

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

By Sara Gambrill, contributing editor

There is an enormous amount of data generated by post-approval research, but one of the nagging questions is: how can researchers get even more, better data and refine it into information that plays a role in decision-making by regulators, biopharma, physicians, insurers, and patients, ultimately improving health outcomes? Speakers at the two-day Post-Approval Summit in Boston (www.postapproval.com) shared a myriad of ways in which they were already embarking on this quest, and some of the highlights are shared below.

Janet Woodcock, M.D., director of the CDER (Center for Drug Evaluation and Research)atthe FDA, gave the keynote, during which she described a dizzying number of government initiatives that spanned from preclinical animal toxicology testing to packaging design. Particularly notable about her presentation was her emphasis on the importance of the patient experience and transparency in the FDA’s decision making about drug safety.

Importance of Patient Experience
Even though clinical drug trials have become more complex, requiring many more procedures to test for safety — and therefore requiring more time, money, and human subjects — the safety profile at approval is still a prediction, according to Woodcock. The safety profile is modified by real-life performance of the product tested. Unanticipated activities, such as inappropriate prescribing, medication errors, misuse, and abuse, all modify the safety profile.

Woodcock described the need for a better feedback loop where findings made in the clinic and postmarket experience would be communicated back to the bench and considered. Pre-approval, a mechanistic understanding of drug toxicity is needed, and she described several ways this understanding is being accomplished in the areas of hepato- and renal toxicity.

Woodcock also noted the importance of the patient’s experience of his or her own disease and impact of treatment. Patients can capture positive and negative impacts of drugs on themselves and relay the adverse events often neglected (e.g. negative impact on sexual function or cancer chemotherapy toxicities) as cancer patients live longer on new drugs, she said. A few initiatives, such as the Critical Path Institute’s PRO and ePRO Consortia, are setting out to create instruments to capture patient-reported outcomes that can migrate from paper to electronic device and device to device that the FDA can then qualify [See June issue of Life Science Leader]. In addition, the CDER’s framework for improving benefit-risk analysis, in pilot stage now, will become part of the FDA review process, and patients’ thoughts and opinions will be considered when benefit-risk is determined for drug therapy.

Better Communication, Increased Workforce
In the interest of providing greater transparency, the FDA is publishing articles describing its safety decisions and the rationale for its decision-making, especially post-market decisions, in various medical journals. The FDA wants the general public to understand how the agency thought through a decision and some of the trade-offs involved in designing a program for the post-market period.
The FDA also wants to improve communication to patients. While the agency provides medical guides now, it hopes to be able to provide patient information in a single leaflet electronically on the patient’s device of choice. The agency wants the information to be incorporated into electronic health records and electronic prescribing systems.

The FDA also finally is addressing its obvious workforce shortfall in handling 15-day reports of serious and unexpected events by installing a new pharmacovigilance system. In 2008, the agency received 300,000+ of these reports, and, as Woodcock pointed out, the FDA does not have 300,000 on staff to read all of them. While it is surely not planning to hire 300,000 new staff, it is creating a “super office” that will employ more people to evaluate these reports in a timely manner. There also is a new data mining initiative at CDER. But, there may be a problem. Where will the agency find employees qualified to do this work?

Judith Glennie, PharmD., MSc., who co-chairs the Real World Outcomes Task Force at DIA, shared during her presentation that the task force has studied the potential workforce needs in real-world setting research and discovered that 75% of those surveyed from pharma, CROs, academia, government, payers, and other related organizations anticipate they will perform more real-world outcomes research during the next three years. She also described lack of funding and various knowledge gaps as being barriers to performing, and advancing the application and use, of real-world outcomes. Training this workforce is an area of opportunity that DIA is exploring.
On a panel, regulators from Europe and Canada as well as representatives from industry operating in the United States and Europe and U.S. academia all described an array of activities and safety initiatives by their respective governments to improve the utility of findings from post-market research and/or communicating them to patients.

The “Fourth Hurdle” For Sponsors: Reimbursement
With greater government involvement in and closer scrutiny of postmarket research, it’s no wonder drug manufacturers would start incorporating post-approval considerations in their clinical trials. In addition to the traditional considerations of quality, safety, and efficacy, reimbursement considerations have been added. The delineation between the pre-approval setting and the post-approval setting is becoming more obscure, according to David Recker, M.D., senior VP at Takeda. There is an increased blurring of the stages of development, according to him, and an earlier understanding of drug information on quality efficacy and safety but also relative competitiveness is necessary now. Post- approval considerations have increased due to the passage of FDAAA (Food and Drug Administration Amendments Act) in 2007, which allows the FDA to require sponsors to conduct additional post-market trials. Comparative effectiveness considerations also have increased due to more scrutiny by the Centers for Medicare & Medicaid Services as well as by private health plans across the country.

Comparative Effectiveness Research (CER): New Approaches, New Initiatives
The second day of the summit was dominated by discussion about comparative effectiveness research initiatives. While everyone was quick to point out that “comparative effectiveness research was nothing new” — one representative of NIH described its history starting with the practice of bloodletting hundreds of years ago — there is certainly a lot of recent activity in the area.

The day kicked off with Troyen Brennan, M.D., MPH, executive VP and chief medical officer of CVS Caremark Corp speaking remotely from company headquarters to describe the role of the pharmacy benefit manager in undertaking CER. CVS Caremark provides benefits for 60 million people, or about 20% of the U.S. population. The organization is setting out to conduct its own completely self-financed CER on medications through its CVS Caremark Pharmacy Institute, which is in the process of being established.
Through activities including literature review and de-identified data from medical and pharmacy claims databases, the institute plans to identify specific areas of research on how to better use certain medications. The objective is to conduct research that will improve decisions about whether new medications are cost-effective from the perspective of quality-adjusted life years (QALYs). CVS Caremark plans not only to publish its findings but to cite them when negotiating the price of drugs with pharmaceutical manufacturers as well as consider them when deciding which drugs to add to the formulary. Brennan alluded to the increasingly generic world for treatment of common chronic diseases and the uphill climb for new medications in this area.

Brennan also wants to see the Institute move beyond CER to survey patients on specific health outcomes, studying doses and combinations of drugs that work best in certain populations for certain conditions and diseases. The plan is to partner with academia and give it full access to and control of this data. The institute also will work more directly with physicians, offering point-of-care advice, especially in high-cost areas such as oncology. Eventually, as physicians prescribe medications, CVS Caremark would like to provide them with real-time information.

Later in the morning, John Santa, director of the Consumer Reports Health Ratings Center, gave his opinions about the present-day healthcare delivery system in a forthright, even bumptious, manner. He claimed that the current CER playing field was not level, as industry — predominantly pharma — dominates the flow of information to consumers in various ways through the billions it spend in direct-to-consumer advertising, physician marketing, and what he termed a “biased research enterprise,” though all these activities are regulated. He stressed that consumers should be involved in appropriate comparison effectiveness tasks, including research, and cited the efforts of Institute of Medicine, the Agency for Healthcare Research and Quality (AHRQ) [see below], the Patient Centered Outcomes Research Institute, and NIH to engage patients. He also acknowledged that patient engagement can be difficult.

As the Consumer Reports enterprise is built on comparisons, it is no surprise that Santa would assert that consumers are interested in them. What he has found of late, however, is that they are most interested in articles about comparisons of healthcare, which have more media impressions on the Consumer Reports website than articles about cars or electronics. Three of the magazine’s top 10 articles of all time, in terms of readership, are about health, he said. Surveys of the magazine’s readers show that they are eager to use comparative data in their decision making about healthcare — from which supplements to take, to which preventive cardiovascular tests are worthwhile. To that end, the industry-independent publisher with 20-million older, affluent, well-educated readers per month is going to launch ConsumerReportsHealth.org.

Patient Registries
Elise Berliner, Ph.D., director of the technology assessment program at the Center for Outcomes and Evidence, AHRQ, described the additional chapters in the second edition of its handbook, Registries for Evaluating Patient Outcomes, first published in 2007. The titles of the four new chapters indicate the new challenges organizations that have created patient registries have encountered since the handbook first came out. The new chapters are: “Planning for the End of a Patient Registry,” “Use of Registries in Product Safety Assessment,” “Linking Registry Data: Technical and Legal Considerations,” and “Interfacing Registries with Electronic Health Records.”

Case presentations given by representatives from various therapeutic area societies and colleges about their respective patient registries rounded out the afternoon’s conference proceedings. All presenters demonstrated the effectiveness of their respective patient registries in providing information that, when applied, improved patient outcomes. Clearly, patient registries are a growing area of interest, given the presence of many disease foundation representatives at the conference. An invitation-only workshop on the subject was scheduled for the next morning.

Studying the best options in terms of patient health outcomes through CER, post-market studies, and patient registries is on the increase. As the rate at which all stakeholders in healthcare can collect and evaluate patient data continues to accelerate, the information gleaned from them will be applied to real-world healthcare settings in meaningful ways much more quickly — a positive outcome for all.