Thank you for the opportunity to speak today. My name is Dr. Laura Gottschalk. I received my Ph.D. from Johns Hopkins School of Medicine and previously worked as a cancer researcher. I am speaking today on behalf of the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers, and policy makers. We do not accept funding from pharmaceutical companies, and therefore I have no conflicts of interest.
The passage of the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act has resulted in labeling changes for hundreds of drugs so that they may be used in pediatric populations. However, despite this success and advances in both basic science and clinical trials in pediatrics, off-label drug use in children and adolescents remains a problem. Moreover, off-label use of drugs presents an even larger and more complex issue for children with chronic and/or rare diseases like the cancers discussed here.
That’s why we strongly support FDA advisory committee meetings, such as this one, to garner input from experts on how best to conduct clinical trials in pediatric patients. The panel has done a great job in asking specific questions of the drug sponsors on their trial design while also offering helpful suggestions and input when needed. However, despite the extraordinarily rare populations of patients to test these drugs, the scientific integrity of these trials needs to be kept in mind while moving forward. When possible, randomized or well-matched control group/comparison samples for new drugs should be used, because it is the ethical and scientifically valid design for proving whether a product is safe and effective. When a proper control group is not available, a robust single agent response rate should be observed in support of drug efficacy.
During the analysis of these proposed clinical trials, also keep in mind the possible pitfalls associated with using biomarkers and surrogate endpoints in lieu of overall survival. A study published last year looked at cancer drugs approved over 5 years using surrogate endpoints. In post-market studies, only 14% of these approved cancer drugs were found to improve patients’ survival. And yet, our Center found that all the unproven cancer drugs were still on the market, many costing more than $100,000 per year. These results show that surrogate endpoints such as objective response rate too often provide false hope while costing patients more they can afford.
Additionally, as discussed with several of the drugs, there are clearly subpopulations of patients who respond better to treatment than others. We encourage the sponsors to further characterize the positive responders in hopes of targeting the population of patients who would benefit the most from their treatment.
In conclusion, we realize that all five of the drugs discussed at this meeting are for treating very rare pediatric cancers that desperately need new treatments. For that very reason, if approved, these drugs may be tempting to use off-label in pediatric patients. Therefore, we commend the FDA and the panel for providing an open discussion on the best way in which to test these five new drugs in pediatric populations. This is a step in the right direction to help ensure that drugs are safe and effective for everyone for whom they are prescribed.
Thank you for your time.