The 2012 AACR Annual Meeting featured a new meeting track designed to draw attention to recent advances and challenges in regulatory science and policy.
This track consisted of five sessions incorporated into the regular scientific program with the goal of drawing attention to the scientific needs of regulators and examining the policy issues facing both cancer researchers and regulators. This new initiative was spearheaded by the AACR Regulatory Science and Policy Subcommittee, chaired by Dr. Frank McCormick.
See also: 2012 Annual Meeting Science Policy Track
HIGHLY ADAPTIVE TRIALS IN DRUG DEVELOPMENT: SCIENTIFIC AND REGULATORY CONSIDERATIONS
Adaptive design refers to a clinical study design that uses accumulating data to decide how to modify aspects of the study as it continues, without undermining the validity and integrity of the trial. Through draft guidance outlining best practices for planning and conducting these studies, the FDA has acknowledged the potential benefits of adaptive design approaches, such as more efficiently providing the same information; increasing the likelihood of success on the study objective; and yielding a broader understanding of a drug’s effect. This session discussed adaptive approaches in both early and late drug development, including highly adaptive studies that are underway, such as the ISPY2 trial, which have the potential to accelerate identification of effective drugs for specific patient populations.
- Sue-Jane Wang, U.S. Food and Drug Administration, Silver Spring, Md.
SCIENTIFIC AND REGULATORY CHALLENGES IN CO-DEVELOPMENT OF PREDICTIVE IN VITRO DIAGNOSTICS
There is increasing interest in the use of predictive biomarkers to improve the therapeutic index of new anticancer agents. The recent simultaneous approval by FDA of two cancer therapies and their respective companion diagnostics along the recent draft guidelines on companion diagnostics provide some insight about the expectations of regulators, yet significant challenges loom. This regulatory uncertainty surrounding co-development is a potential disincentive to the development of such personalized therapies. This session aimed to address current challenges and regulatory considerations in the co-development of therapeutics and predictive in vitro diagnostics (IVDs).
- Mark J. Ratain, University of Chicago, Chicago, Ill.
- Janet Dancey, Ontario Institute for Cancer Research, Toronto, Ontario
- Samir Khleif, Georgia Health Sciences University Cancer Center, Augusta, Ga.
PATHWAY VERSUS HISTOLOGY IN DRUG DEVELOPMENT
As science deciphers the molecular drivers of cancers and more therapies are developed against specific aberrant targets, it raises the possibility of selectively accruing patients into clinical trials based on biology and the cellular abnormality specifically targeted by the investigational agent, rather than designing trials which select patients on anatomic site of tumor origin or histology. This session provided an overview of the scientific and regulatory issues surrounding multi-histology clinical trial designs that focus on a molecular pathway rather than a specific tissue origin. Panelists explored whether clinical investigators, governmental and biopharmaceutical sponsors and administrative regulatory systems are now ready for multi-histology trials, and if not, how best to pursue the most promising molecular targeting in enriched patient populations to speed rational testing of clinical activity. This session also touched on challenges of implementing and interpreting current molecular and genomic diagnostic technologies in the design of clinical trials.Moderator:
- Janet Woodcock, U.S. Food and Drug Administration, Silver Spring, Md.
- Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne, Australia
COMPARATIVE EFFECTIVENESS AND IMPLICATIONS FOR TRIAL DESIGN
This session examined the complexities surrounding the different evidence demands of regulators and health care payers, touching on differences between Europe and the U.S., and also presented current and emerging scientific approaches to comparative effectiveness analyses. Comparative effectiveness research is designed to provide evidence on the effectiveness, benefits, risks and harms of different treatment options. Regulatory review (FDA, EMA), on the other hand, is aimed at determining the benefit/risk ratio of a treatment. Studies designed for regulatory review typically do not take into account all other treatment options or consider whether results of well-controlled trials are generalizable to the real-world clinical practice, where patients are treated in less-controlled clinical environments and often present with multiple co-morbidities. This session addressed definitions of often-used terms and explain effectiveness and comparative effectiveness research, the current status of guidelines of regulatory bodies (EMA, FDA and health insurance and health care agencies) and how to perform comparative effectiveness research in order to determine the best treatment.
- Jan Schellens, The Netherlands Cancer Institute, Amsterdam, Netherlands
CO-DEVELOPMENT OF TWO OR MORE INVESTIGATIONAL DRUGS
Scientific and technological advancements are allowing researchers to identify specific combinations of cellular molecules that, together, drive cancer proliferation and malignancy. Co-developing agents that target these combinations has the potential to improve the effectiveness of cancer treatment. This session focused on the scientific and regulatory considerations for developing two or more investigational agents for use in combination for a single indication. The FDA draft guidance on codevelopment was also discussed.
- Frank McCormick, University of California San Francisco, San Francisco, Calif.
- Jeffrey A. Engelman, Massachusetts General Hospital, Boston, Mass.
- Roy S. Herbst, Yale Comprehensive Cancer Center, New Haven, Conn.