Clinical Trials What are controlled clinical trials? Why do we need them? The term “Clinical Trial” typically refers to a research study that evaluates a new treatment or intervention. The new treatment is given to patients under very controlled circumstances to make sure that participants are safe and so that any important changes noted among treated patients can be attributed to the treatment and not to external factors. As with every serious disease for which there is no cure, physicians and patients alike strive for effective treatment and are understandably ready to embrace any new hope. This aspect of human nature is well captured in the expression “grasping at straws” and makes it difficult to establish whether a new therapy is helpful or harmful. Everyone wants to take the new treatment and everyone involved wants to believe that it works. The history of medicine, however, has many examples of treatments that were associated with considerable discomfort, cost, or even danger, and that were used on many patients until finally they were proven ineffective or even harmful in controlled clinical trials. Also, so-called “open” trials in which everyone receives the new treatment are prone to providing overly optimistic and inaccurate results concerning treatment benefit because of the so-called “placebo effect”. For this reason, good clinical trial design requires a comparison group that is not receiving the new treatment. Controlled clinical trials are now widely accepted standards in medical research. Most patient advocacy groups, including networks of cancer and HIV patients, support controlled clinical trials. The FDA requires proof of safety and effectiveness in controlled trials before approving any new medication. The National Institutes of Health guidelines for funding of clinical research encourage medical researchers to design rational, controlled trials. One question that families frequently ask is why some participants will receive a placebo (inactive drug) during at least some periods of a trial. They are wondering whether it would not be better for them to be sure to receive the active medication. We understand this reasoning and we try to keep the number of patients on placebo as small as possible without compromising our ability to determine the actual effects of the treatment. However, we feel that it is our responsibility as physicians and researchers to subject new treatments to controlled clinical trials for several reasons. If we were certain that a new treatment would help patients with SMA, we would not have to do a clinical trial. If at any point during the trial it became clear that patients taking a new medication do significantly better or worse than those without the new medication, the trial would be stopped and we would be able to give the appropriate recommendations to SMA patients. Until and unless we have these results, the best way that individual patients with SMA, their family members, and the community of SMA patients can obtain crucial information on the safety and efficacy of a new medication is through a randomized, double-blind (whereby neither the patients nor the clinicians know who is receiving the new treatment), appropriately controlled trial. We strongly believe that participation in controlled clinical trials is in the best interest of patients with SMA and their families. Especially when dealing with relatively rare diseases, it is of crucial importance that potential therapies are investigated at designated research centers and in controlled trials. In doing so, patients and researchers will have the greatest chance to reach their common goal, that is, to improve the situation of patients with SMA as soon as possible. These studies greatly reduce the inconvenience, risk, and expense that many patients and family members encounter when they feel obliged to take suggested treatments without knowing whether the treatment will actually help or when they should stop taking it. Clinical trials allow us to rationally test treatments, eliminate harmful or ineffective treatments rapidly, and, hopefully, find an effective and safe treatment soon.