Research Faces Challenges in 2010

The global economic downturn, the contentious debate over national health reform, and important changes on the regulatory front have had a toll on biomedical research and new drug development. The new year brings optimism for clarity on health care coverage and regulatory requirements. National health reform legislation either will become law in some form, or die a painful death.

Jill Wechsler

The new team heading up the Food and Drug Administration will be firmly established and eager to implement new policies and programs. Research sponsors will be consolidating operations following major industry upheavals. All will be watching key trends and developments that will shape drug research in 2010:

Pharma globalization. The rising importance of overseas markets for drugs and medical products is prompting industry to become more firmly established in China, India, Brazil, and other newly industrialized nations. Pressure to cut production and research costs at home are driving more foreign ventures. Tapping these growth markets involves more industry investment in new treatments for malaria, tuberculosis, and neglected tropical diseases.

FDA is actively encouraging such efforts and is likely to do more under commissioner Margaret Hamburg, who has a strong background in public health and infectious disease. The agency is supporting development of new tuberculosis treatments to replace ineffective old therapies and promoting its priority review voucher program as a way to stimulate industry R&D.

To better monitor the growing volume of pharmaceutical imports and foreign clinical trials, FDA also is establishing overseas offices and doubling the number of foreign inspections it conducts each year. And a collaboration between FDA and European regulatory authorities to share inspection information and conduct joint inspections could expand if beneficial.

Invigorating vaccines. The battle against infectious disease has spurred worldwide investment in vaccine development and production, and this surge is slated to continue. Global funding of a vaccine to combat the H1N1 influenza pandemic has financed construction of vaccine manufacturing faculties in the United States and abroad. New vaccines to combat malaria and TB are in clinical trials, and scientists remain optimistic about moving forward with the long-sought vaccine to prevent HIV infection. Novel antigens are in the works; an anti-smoking vaccine is moving into late-stage testing; and scientists continue to seek therapeutic vaccines for cancer and other conditions.

Drug safety and risk assessment. FDA is involved in multiple initiatives to ensure the appropriate use of approved medicines through the product life cycle. The FDA Amendments Act of 2007 (FDAAA) authorized postapproval label changes when new safety issues arise and penalties for manufacturers that fail to conduct agreed upon postmarketing studies. There are mandates for a more extensive listing of clinical trials and study results on the ClinicalTrials.gov public Web site and for Risk Evaluation and Mitigation Strategies (REMS) governing postmarket prescribing and surveillance.

FDA has approved REMS for almost 90 products and is formulating a REMS for the entire class of extended-relief opioid medicines; a more coordinated risk management strategy aims to ensure continued access to these medications for patients suffering from chronic pain, while also curbing inappropriate prescribing, unintentional overdosing, and intentional abuse.

Sponsors, researchers, health professionals, and patient groups will be watching closely to see how well these programs detect and prevent drug safety problems, and whether these efforts support more FDA flexibility in approving somewhat risky new products for market. Internally, FDA is bolstering its safety assessment capabilities through several initiatives.

A Safety First program in the Center for Drug Evaluation and Research (CDER) is integrating oversight of safety issues by clarifying responsibilities for pre- and postapproval drug safety assessment and strengthening safety-related policies and procedures. The agency's Sentinel Initiative aims to monitor medical product safety more effectively through an electronic monitoring system linked to health care databases. Starting with several pilot projects, the system eventually will be able to detect emerging safety problems in real time and identify patient subgroups experiencing adverse events.

And FDA's Safe Use initiative, which commissioner Hamburg announced in November, aims to build partnerships with other components of the nation's health care system to ensure that medicines are used safely and appropriately. FDA plans to partner with other government agencies and with health care providers to address situations that lead to medication errors and inappropriate prescribing.

IT adoption. Developing the Sentinel System for monitoring drug safety requires access to electronic health information systems, a prominent goal of national health reform. Earlier economic stimulus legislation jump started this effort by providing $19 billion to support use of electronic health records by doctors and hospitals and to develop standards and systems supporting electronic health information exchange. Electronic databases promise to accelerate detection of drug adverse events and to streamline data collection from clinical trials and population studies.

At the same time, broader access to personal health information has generated demands for stronger protections against unauthorized disclosure of patient records. The concern for the biomedical research community is that privacy issues could limit access to patient information needed for preclinical and postapproval studies. An expert panel organized by the Institute of Medicine recommends simplified approaches to clinical research that utilize a distributed model for health surveillance and assessment based on the data-sharing capabilities of electronic information systems, an approach that will gain more notice in coming months.

Personalized medicine & comparative research. Electronic health information systems are critical for the development of personalized, or individualized, therapies and the diagnostics needed to determine who may benefit or experience harm from more targeted treatments. The shift to personalized medicine requires access to personal health data to recruit research subjects who meet increasingly specific genetic-based enrollment criteria, and to identify those individuals who should—or should not—receive a treatment based on specific genotype.

Researchers also will be tapping health system databases to assess outcomes and to compare the risks and benefits of medical products. Federal agencies are funding a number of comparative effectiveness research (CER) projects with an eye to assessing a broad range of medical treatments and strategies. Pharma companies seek limits on government-funded studies that compare one drug to another and focus on cost comparisons, but more CER will inevitably highlight comparative prices as well as health benefits.

Prices & pathways. Whatever the outcome of health reform legislation, prescription drug prices will remain in the spotlight. Broader coverage of pharmacy benefits could reduce public complaints about high drug costs, but consumer groups and health care providers will continue to complain about expensive medicines that block patient access to treatment. Both Wall Street analysts and patient advocates documented record increases in wholesale drug prices this past year, despite very low inflation. The studies exposed manufacturers to charges of jacking up revenues in anticipation of tighter controls on pharmacy spending.

Such developments will continue to build support for access to generic drugs, including follow-on biologics. Congress is poised to establish a regulatory pathway for approving biosimilars for market, based on agreement among generics makers and innovator firms on FDA regulatory standards and clinical testing requirements. But the 12-year exclusivity for innovator products sought by biopharma companies has infuriated generics makers. Manufacturers on all sides will be assessing how these policies will shape biosimilar development.

More disclosure. "Transparency" is a recurrent theme in health reform and regulatory matters. Efforts to lower drug prices could involve broader disclosure of manufacturer rebates and discounts negotiated by payers and health plans. Congress further seeks to shed "sunshine" on drug company payments to physicians as a way to reduce industry influence on prescribers.

More transparency in FDA regulatory decisions also is on the horizon. Commissioner Hamburg established a high-level transparency task force last June to identify ways to better inform the public about FDA operations—and enhance agency credibility in the process. The panel headed by FDA Deputy Commissioner Joshua Sharfstein is examining whether FDA should be able to disclose when an application is filed, withdrawn or turned down by FDA; to discuss data in abandoned applications; and to reveal the contents of complete response letters sent to sponsors.

Also under review is when emerging safety information should be disclosed and whether early communication about ongoing safety reviews would be beneficial or raise unnecessary concerns. The panel will issue a report in the coming year on what information FDA should be able to release on its own, and what changes require new regulations or legislation.

Jill Wechsler is the Washington editor of Applied Clinical Trials, (301) 656-4634 jwechsler@advanstar.com 466666464634Washingtonbold_bylineemail