An Analysis of the Feasibility of N-of-1 Clinical Trials for the Market Approval of Pharmaceuticals

Abstract

Randomized controlled trials are the cornerstone necessary for the testing and analysis of pharmaceuticals prior to gaining market approval. Implementation of these trials since the establishment of the Food and Drug Administration has resulted in the approval of thousands of drugs. Importantly, they have also alerted the Agency to drugs that are not safe or well-tolerated by the general population or are not efficacious, as thousands of people are enrolled in multiple trials over the course of clinical development. Despite the benefits of conducting randomized controlled trials and their ability to assess market readiness for the patient population for which the drug is intended, results from clinical trials are not always indicative of how the drug will perform in an individual. Many approved drugs do not have the same efficacy levels in individual patients as demonstrated in clinical trials, leading to patient frustration with the pharmaceutical industry. More advanced treatment options are emerging in the form of personalized medicine which considers disease management of a single patient. The increase in this trend elicits the need for assessing the role of randomized controlled trials in pharmaceutical development. Personalized medicines should be evaluated with modified studies that assess each patient on an individual basis. Randomized controlled trials do not have the ability to do this, as they measure effects in a group of patients as a whole. The use of N-of-1 clinical trials is a necessity as the field trends towards personalized treatment, as they measure the effect of a drug on the individual and can additionally draw conclusions of safety and efficacy for a group of patients. An extensive literature search was performed to evaluate the use of N-of-1 clinical trials with respect to the pharmaceutical industry. Major aspects of clinical development, such as trial design, statistical analysis, data reporting, and regulatory guidelines were analyzed to determine the comprehensiveness of these trials. This case study reveals that N-of-1 clinical trials have established design criteria, methods of statistical analysis, and reporting guidelines that would allow these trials to be used in pharmaceutical development. They are satisfactory to use alone for rare diseases and small patient populations and may be used as supplementary trials for diseases with larger populations or for post-marketing studies for assessment of drug use for additional indications.