The Future of Clinical Trials: Novel Trial Designs to Improve Efficiency

Randomized clinical trials (RCTs) are the gold standard for clinical research. In recent years, RCTs became unnecessary complicated, they are crumbling under modern economic, scientific and regulatory pressures and drug companies are removing more compounds from pipeline than ever before because many promising drugs fail to meet milestones for safety/efficacy reasons. Interestingly, patient recruitment and retention remains as a major stumbling block for drug development. Thus, fundamental changes are needed to make the process of drug development shorter, more efficient and cheaper. First, it is important to understand the mechanism of action (MOA) and the pharmacological properties of the new drugs before pivotal clinical trials are performed. Second, phase 2 trials are critical to confirm the MOA and validate the target in humans, select the dose and most suitable patients according to the MOA using biomarkers for predicting clinical efficacy and safety and genomic markers for identifying the right population. Phase 3 trials must incorporate primary endpoints based on MOA, right clinical efficacy measures and focus on patients that most likely to benefit. Rigorous safety analysis is crucial from early development. Third, main changes in the development of RCTs include that sponsors and CROs embrace new ways of patient recruitment and retention, replace sites by Consortia, decrease burocracy and improve how information is exchanged among partners using cloud computing and, most important, became familiar with adaptative clinical trials. Based on the analysis of the accumulating information they allow to identify the best dose early, to stop the trial if there are adequate indications of lack of safety or efficacy, re-estimate the sample size, drop ineffective arms and add new arms and change the trial hypothesis. However, adaptive designs require intensive planning and are not a substitute for poor planning.