How can oncology drug developers accelerate oncology clinical trials? In March 2023, the Food and Drug Administration issued a new guideline [1] that provides tips on how to design clinical trials for Accelerated Approval in oncology.

What is an Accelerated Approval? Drug developers developing new treatments for life threatening diseases, can seek approval on the basis of surrogates. A surrogate is an endpoint that is able to predict for efficacy. For example, in oncology, tumor response is a good surrogate, as is time to progression. If the time to progression can be increased, over the standard of care comparator group, there is good reason to believe that the treatment will improve a hard clinical endpoint that is meaningful – i.e. survival.

There are many challenges of designing clinical trials for oncology. Some questions that need to be answered are:

  1. What types of oncology patients will the drug be helpful to?
  2. What stage of disease will the patients have?
  3. Do patients we want to study already have access to other effective treatments?
  4. What is the Phase of study, and could the results support Accelerated Approval?
  5. How long will the study take to complete?
  6. What other treatments are will be available by time the study is completed?
  7. Will the study results still be relevant given any changes in the treatment landscape?

Designing clinical trials for life threatening diseases is challenging. These studies can take 2-5 years to complete. By time the study has been completed, the standard of care may have changed. The results achieved may be difficult to interpret, or may not be as meaningful as they would have been some years before.

When clinical trials are not randomized, the results will be difficult to interpret. Bias will almost certainly be introduced into non randomized studies, especially if steps were not taken to reduce the introduction of bias.

When there are other treatments available, design studies that are randomized against the standard of care, or a treatment that has already achieved approval. Use designs that address these patient concerns, such as randomization to older treatments.

Historical controls have their place, and they have become more important in recent years. Be aware that use of historical controls from years ago, when the standard of care was different, or the concomitant treatments were different, may complicate the interpretation of data. Another challenge is it may not be feasible to obtain the study reports for the publications which the historical controls were based on.

Presumably the guidance is given because of the number of challenges the FDA sees, indicating clearer guidance is neede.

To receive expert advice on the design of clinical trials for Accelerated Design Programs, contact Dr. Lorna Speid at LSPEID@SNDTM.COM with Accelerated Approval in the subject line.


  1. FDA Guideline, Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics, Food and Drug Administration. March 2023.