Phase II Trials for Drug Licensing: Analysis Shows That Efficacy Is Often Overestimated

Based on a systematic analysis of all recently published trials in the field of rheumatoid arthritis and psoriatic arthritis, a study group at the Medical University of Vienna and the division of rheumatology at Vienna General Hospital has found that the results of phase II drug trials systematically overestimate the efficacy of therapeutics and, as a result, the subsequently conducted phase III trials often produce disappointing results.¹
Phase II trials are typically small, and are conducted to assess the optimal dose and estimated efficacy of a  new drug in the relevant patient group. If phase II trials are successful, they are usually followed by phase III trials. Phase III clinical trials are the ultimate precursors to new drugs for clinical use. Such study programs are often conducted on a large scale and are very expensive, since they require a lot of participating volunteers, including for placebo control groups. In most cases, drugs that have successfully overcome this hurdle have also made it onto the market.

The findings of the Vienna researchers have dramatic implications for sponsors of clinical trials and also for academic groups and patients. Lead author Andreas Kerschbaumer was able to identify that the problem is primarily due to liberal inclusion criteria for phase II trials. Disappointing results can be avoided by a more careful and stringent choice of inclusion criteria and of the trial population.

“These results show quite clearly that the problem that has been identified does not only apply to a single disease but to others as well,” says principal investigator Daniel Aletaha, MD. “Moreover, the data indicate that the problem discovered using rheumatology relates to all other disciplines.”

Many existing drugs are being seen as offering hope of a successful covid-19 treatment, but small trials conducted so far have not borne out these expectations. The Vienna researchers draw parallels from their study to the numerous covid-19 trials currently underway: “Our results are particularly important in view of the many phase II trials that are to be expected for covid drugs, because it is important to plan the phase II trials in such a way that they are actually meaningful and can then be confirmed in the costly and time-consuming phase III, rather than being refuted.”

Reference

1. Kerschbaumer A, Smolen JS, Herkner H, Stefanova T, Chwala E, Aletaha D. Efficacy outcomes in phase 2 and phase 3 randomized controlled trials in rheumatology. Nat Med. Epub April 20, 2020; doi: 10.1038/s41591-020-0833-4.