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The Food and Drug Administration has been rolling out key guidances and implementing new policies in recent weeks, striving to encourage research on new drugs and diagnostics by clarifying its expectations and standards for testing experimental products. Some proposals are highly controversial, and all are likely to generate comments from stakeholders on all sides.
One potentially important development involves utilization of priority review vouchers, long championed by economists as a way to provide added rewards to companies that discover new treatments for rare and tropical diseases. So far the voucher program has had little impact, but its recent extension to pediatric rare diseases may be more fruitful. FDA awarded the first pediatric disease voucher last February to BioMarin, and in July the firm sold the option for a speedy review to Sanofi and Regeneron for $67.5 million. The buyers indicated that they intend to seek faster FDA approval for a new cholesterol treatment with blockbuster potential. Similarly, last month Knight Therapeutics said it would sell its priority review voucher, this one for a tropical disease treatment, which carries more restrictions.
Another regulatory “breakthrough” is the joint approval of a new diagnostic under the parallel review program established by FDA and the Centers for Medicare and Medicaid Services (CMS). The aim is for CMS to issue a national coverage determination for Medicare reimbursement of the product at the same time FDA approves it for market. After years of effort to implement the program, the agencies finally announced last month simultaneous agreement on coverage and approval of a non-invasive colorectal screening test, Cologuard, developed by Exact Sciences. Success in this area requires clinical trials to generate data on product effectiveness and value, as well as efficacy and safety. The program currently is limited to devices, but could be extended to drugs if found to address public health needs.
New FDA guidance also aims to encourage the development of more companion diagnostics (CDx), considered key to advances in the personalized medicine arena. The Center for Devices and Radiological Health (CDRH) published a long-awaited advisory last month, designed to help research sponsors address the considerable challenges in bringing to market both a new drug and companion test product. The guidance on “In Vitro Companion Diagnostic Devices” indicates those situations where FDA may approve a new therapy without a CDx and clarifies how labeling should explain appropriate drug-diagnostic use.1
In a related action, the agency recently announced its intent to regulate laboratory-developed tests (LDTs)—or “homebrews” developed by individual labs—which can be integral to product development and appropriate use of approved therapies, but often are not fully tested or evaluated for effectiveness and clinical validity. Both commercial and academic lab operators vehemently oppose FDA involvement in this activity, but agency leaders are concerned that broad use of more complex assays warrants more standardized examination of those diagnostics that offer greater risk to patients.2
There’s much less controversy, and broad interest among sponsors and investigators, in FDA’s new guidance on obtaining informed consent for clinical trials. The draft advisory issued in July does not break new ground in the policy arena, but provides useful clarifications and interesting updates from the 1998 guide. The “Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors,”3 maps out the process for sponsors to inform individuals about the broader clinical research process, the aim of the specific study and the issues to consider in agreeing to participate in a clinical trial.
A main theme to clarify informed consent for “vulnerable populations,” including non-English-speaking people and for individuals with low health literacy. There is extensive discussion about the consent process involving children and who is a “legal representative” for children and adults lacking full mental capacity, including unconscious patients.
Patient advocates complain, however, that FDA should do more to require sponsors to inform trial participants of study outcomes and to encourage more data disclosure. The AllTrials initiative asserts that “sharing” of anonymized individual patient data is highly valuable in advancing and improving medical product development, and thus it’s important to eliminate sponsor claims that informed consent may block such disclosure.
FDA notes that its revisions in informed consent practices aim to coordinate with collaborative efforts by the Department of Health and Human Services (HHS) and other federal agencies to revise the “Common Rule” for all research involving human subjects that is funded or overseen by the federal government. More effective informed consent is a key topic, and its importance also is reflected in the award of a $1.7 million grant to examine patient views on informed consent approaches related to outcomes research. This three-year project at Johns Hopkins University is funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its mandate to examine research methods affecting outcomes studies. The project aims to determine if shorter consent approaches and greater transparency and accountability about a research program affect participation, and resulting insights should be useful to the broader biomedical research community.
These and other research-related issues may be addressed further by the House Energy & Commerce Committee’s “21st Century Cures Initiative,” which has amassed a great deal of information and opinions on FDA regulatory policy, patient R&D perspectives and the importance of economic incentives in spurring developing of needed medical treatments. Broad input from representatives of biopharma companies, academic researchers, and patient advocates at recent hearings and roundtable discussions will provide a basis for Committee leaders on both sides of the aisle to propose legislation early next year.
The legislators will be looking at the value of added incentives for developing new antibiotics and proposals for streamlining and coordinating the clinical research process, among other issues. Many experts spoke to the importance of adequate funding for FDA and for the National Institutes of Health, and this imperative may have some affect on the Congressional budget-setting process, as well as on future user fee negotiations.