Research

Clinical Trials
Clinical Studies
Adaptive Clinical Trial
Design Methodology
#Study Title

Innovative Clinical Trials

Adaptive trial design (ATD) is a methodology in which a clinical trial evolves or adapts as the trial proceeds depending on the outcomes of patients enrolled. The criteria for these decisions are set prior to the beginning of the studies. An adaptive design makes use of standard statistical methods (i.e. frequentist) to halt the trial early for toxicity (dangerous substance), futility (no improvement over a control), or efficacy (great improvement over a control).

ATD has been shown to be an attractive alternative to conventional study designs for several reasons. The most important reason is that it can “learn” from relatively small numbers of study subjects. In our calculations, as few as 8 patients can be used to decide if a therapy is ineffective. Another aspect of ATD that enhances efficiency is that it uses a single ongoing control group rather than having a different control group for each experimental group. Thus, the vast majority of patients can be assigned to an experimental group. This maximizes the number of different studies that can be performed in a small population of patients. ATD also minimizes the number of patients receiving ineffective treatments and thus limits unnecessary treatment risks in study patients. This is an important reason why the FDA has enthusiastically supported adaptive trial design studies.

ATD studies commonly employ a surrogate endpoint to decide efficacy. For example, in cancer studies, a decrease in tumor size is an accepted surrogate endpoint for drug approval. In our studies, we will use the biopsy findings of antibody mediated rejection as a surrogate endpoint. In most cases, however, ATD are used in Phase II clinical trials as a way of efficiently predicting the probability that a given therapy will be successful in a subsequent definitive Phase III trial. If a surrogate endpoint is used, the drug might receive interim approval (ex. under Subpart H or other mechanisms) allowing it to be marketed and sold, but also requiring follow-up on treated patients to show the drug actually improves a clinical endpoint such as patient survival (or graft survival in the case of renal transplantation).

ATD is supported by pharmaceutical companies because it has the possibility of significantly decreasing the time and money needed to show efficacy of a drug. Indeed, it is common for otherwise competing drug companies to support an ATD study jointly in an effort to save money and time using this mechanism.

ATD has not been used in transplantation. We believe that ATD is extremely well-suited for all types of transplantation studies and initially intend to use them in studies in the treatment of late graft loss due to antibody mediated rejection.