By: Sophia Jeon, Ph.D.
Drug regulation and rare diseases
FDA delays decision on whether to approve Sarepta drug for Duchenne
The Food and Drug Administration (FDA) is wedged between a rock and a hard place to decide whether or not the agency should approve the controversial drug, eteplirsen, for Duchenne muscular dystrophy (DMD). DMD mainly affects boys and is considered a rare disease as it affects fewer than 200,000 US cases per year. As the name implies, it is a neuromuscular condition in which symptoms include frequent falling, trouble getting up or running, and learning disabilities. Average life expectancy for those afflicted with DMD is about 25, and there is no treatment. Considering these devastating factors, it is easy to understand why DMD patients, and their parents would want to hasten the approval of a drug that could potentially save their lives.
On the other hand, it is also easy to understand why the FDA is hesitant to approve this drug. The FDA is a regulatory agency and one of their missions is to evaluate drugs to determine whether or not they are safe and effective to be in the market. The issue is with a Phase III study that Sarepta Therapeutics did to test the efficacy of eteplirsen – that the trial was not well-designed making it difficult to come to a definitive conclusion that this drug works. The trial only involved 12 patients, without a placebo control group. If the FDA makes a decision to approve this drug under political pressure from various stakeholders, a drug that potentially could be ineffective for many kids with DMD only gives them and their family false hope and decreases the motivation for pharmaceutical companies to develop more effective DMD drugs.
Understanding patients’ needs, FDA has an expanded access program that, with the FDA’s approval, allows patients to try experimental drugs. In addition, the Orphan Drug Act gives pharmaceutical companies more incentive to develop drugs for rare diseases. However, it is clear that patients whose lives are on the line do not think the drug development is happening fast enough and are willing to try any option they have available. In 2015, there was even a bill introduced, called Right to Try Act that allows patients to have access to an experimental drug without the FDA’s approval. How much should public input or influence be taken into account in a drug approval process? Should FDA have better strategies in effectively communicating and engaging with patient groups? These are some good questions without definitive answers. (Ed Silverman, STATnews)
Research evaluation and bibliometrics
The pressure to publish pushes down quality
Let’s look at our current research culture. Whether or not you get an academic position, a grant, or a renewal of a grant all depends on how much you publish. “Publish or perish” is a phrase that is frequently used in academic science and it definitely rings true for many researchers in the US. People evaluate your research and productivity based on the number of your publications and the impact factor of the journals you publish in. Daniel Sarewitz recently wrote in Nature about the negative consequences of promoting this “publish or perish” culture.
The first problem is that increasingly everyone in research, whether conscious of it or not, seems to be contributing to this culture, and we need a cultural shift, which does not happen overnight. However, there are efforts to change the way we evaluate science. For instance, Declaration on Research Assessment (DORA) was initiated by the American Society for Cell Biology with a group of editors and journal publishers to try to make that cultural shift and start the movement for everyone in science to realize that merely an impact factor or how many times your paper has been cited should not and cannot accurately reflect your productivity, assess your work’s value or even define your career.
The second problem that Daniel talks more about in this article is the problem of rigor. Some researchers are so pressured to publish that they end up do things that are unethical or produce hard-to-replicate findings by experiments that are not rigorously designed. Researchers also sometimes exaggerate the importance of their findings in order to publish or hand-wave at any inconsistencies in their discussion sections. The real harm is done not only when other researchers waste time trying to chase a false lead but also when these not-rigorously-tested studies accumulate to adversely affect public health. A popular example is the study done by Andrew Wakefield who published his (false) claim linking the MMR vaccine to autism. These problems should not just stop at being “concerns,” instead it is time to re-think the strategies of evaluating science and doing science. Scientists could do better quality science by spending more time thinking and rigorously testing hypotheses than strategizing how to write an attractive story to publish more in a “high impact” journal. (Daniel Sarewitz, Nature Comments)
Clinical trial design and personalized medicine
Personalized medicine: Time for one-person trials
Biomedical research is in a very unique position right now. Recent technological advances have allowed scientists to easily and economically perform activities such as whole genome sequencing (WGS), big data analysis, mobile health data tracking and tissue and cell engineering. These technologies, especially when used in combination, can be a powerful tool that not only offers scientific insight into human biology but also brings up a number of exciting opportunities for prevention and treatment of diseases. These are a few of many reasons the President’s Precision Medicine Initiative (PMI) is gaining much attention.
With these advanced technologies, scientists are beginning to realize that personalized medicine, not just genetic counseling but one that includes a number of other measures, such as your metabolic profile, lifestyle factors, environmental exposures, etc., is the future of biomedical science. One-person trials hope to address a number of issues that the current clinical research or trial designs cannot address sufficiently such as the fact that people have different responses to drugs, and that there has been a lack of inclusion of minority or health disparities populations in many clinical trials taking place in the US. N-of-1 trials would not only address that issue but also could reduce any ethical concerns for placing patients in a randomized placebo control group especially when there is no standard-of-care, because everyone in the trial would be getting the experimental drug for a certain period of time, wait for the effects to wear off, and then a placebo for another to examine their responses to the drug. (Nicholas J. Schork, Nature Comment)
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