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Agency concerned about how proposals in "Cures" bill will be crafted and implemented.
There seems to be a general agreement among policymakers and in the research community that the Food and Drug Administration (FDA) has done about as much as it can to speedily review and approve important new therapies, and that efforts to facilitate patient access to needed medical products now should focus on accelerating drug development and clinical testing. Thus, the slimmed-down April version of the 21st Century Cures legislation from the House Energy & Commerce Committee (E&C) backs a number of strategies for modernizing and simplifying clinical trials, incorporating patients’ voices into product development, encouraging collaboration on biomarker qualification, and reducing waste and redundancy in the clinical research process.
Under that last heading fall proposals to promote the use of central institutional review boards (IRBs). The legislation authorizes “lead IRBs” to oversee multi-site human subject research, specifying that cooperative research projects could establish a joint or shared review process or utilize an independent IRB; FDA guidance would address the need to incorporate local community values when central IRBs are used.
Another efficiency provision would exempt FDA-regulated clinical trials from also meeting requirements set by the Common Rule. And Congress looks to make it easier for patients to access clinical trial information on the ClinicalTrials.gov website by standardizing data and formats. Even though FDA already is doing much to accelerate biomarker qualification and use of Bayesian statistics and adaptive trial designs, there’s general support for language in the bill emphasizing Congressional support for such efforts.
Several research-related provisions, though, raise red flags. There’s considerable concern about a proposal permitting sponsors to waive informed consent for clinical investigations of drugs and medical devices that pose “no more than minimal risk” to participants. Even though sponsors would have to take “appropriate” steps to protect the safety and welfare of subjects, patient advocates fear this would undermine usual patient safeguards.
Also controversial are research “modernization” proposals with potential to radically alter the biomedical development process. One would authorize greater use of “real-world evidence,” with language requiring FDA to approve certain new indications based on “clinical experience” data from registries and from FDA’s Sentinel System. Another aims to reduce the volume of clinical data supporting market applications by permitting manufacturers of approved drugs to submit “qualified data summaries” in efficacy supplements to gain approval of a “qualified indication.” FDA guidance would clarify this “streamlined data review” system and the types of indications eligible for the program, but critics warn it will undermine usual assurances of drug safety.
More mandates, no resources
As the legislators rolled out their bipartisan draft proposal last month, FDA officials voiced concerns about just how these initiatives would be crafted and implemented, and where the agency would get the resources needed to carry out its many requirements. House leaders authorized a significant budget increase for the National Institutes of Health (NIH), but gave FDA less than $100 million a year to modernize trial design and evidence development. More important is a provision exempting FDA user fees from budget sequestration.
Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), stated at a hearing before the E&C health subcommittee in April that a new law requiring new programs and multiple guidances could undermine her ability to meet review and approval commitments. This latest E&C proposal has “significant resource implications for FDA,” she said, noting that CDER’s new drug review process is now “going at full speed, and we’d like to keep it that way.” Getting new therapies developed efficiently is helped by timely advice from the agency, and that “would be the first to go,” she warned, if the agency gets further stretched on resources.
What FDA sorely needs, Woodcock and other agency officials emphasized, is to cut some of the red tape and obstacles to bringing in the experts able to address complex scientific and regulatory issues. Too-low salaries prompt experienced staffers to leave for more lucrative jobs in industry and academia, and complex government employment requirements make it hard to recruit top talent.
To gain Democratic support for the Cures proposal, Republicans dropped earlier proposals to extend exclusivity on certain innovative drugs and improved formulations. With time now running out to negotiate other contentious issues, the legislators may agree to enact a much smaller “Cures” bill this year: the short list includes further biomarker qualification, a breakthrough program for medical devices, flexibility on communicating drug economic information, broader use of central IRBs, and development of “limited use” antibiotics. There would be more money for NIH, but Congressional appropriations committees will have the final say on funding levels. The rest of the FDA reform items then would be held for further discussion and possible incorporation into user fee legislation in two years.