Are New Clinical Trial Designs Effective?

Jonathan W. Friedberg, MD, MMSc
Director of the James P. Wilmot Cancer Institute and director of Hematologic Malignancies Clinical Research at the University of Rochester Medical Center in Rochester, New York

Among the goals of the ASH Subcommittee on Clinical Trials is to increase accrual to clinical trials within the hematology space, ensure diversity among participants of these trials, and make sure that new drugs obtain approval in the safest and most efficient ways possible. Expedited review programs and adaptive trial designs have led to record numbers of drug approvals in recent years, but questions remain about the safety and efficacy of these agents.

As part of this year’s program, a panel of experts will address the recent surge in hematology drug approvals, and how clinicians should interpret the data behind these approvals, in an Education Spotlight Session called “Approved, But Should We Use It? Are The New Trial Designs Effective?

Here, session chair Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute and director of Hematological Malignancies Clinical Research at the University of Rochester in New York, previews the session.

Why was this selected as a topic for an Education Spotlight Session?

We are in a very exciting time in both benign and malignant hematology when it comes to the pace of new drug development. For example, in diffuse large B-cell lymphoma (DLBCL), there really were no drugs approved for more than two decades. In just the last 18 months, though, we have had four new agents approved. We are seeing that type of progress across benign and malignant conditions.

That has to do, in part, with the fact that the approval mechanisms have changed. In this session we want to discuss these changes from the standpoint of clinical trial accrual and how best to use the approved agents.

Who will be speaking during this session, and what perspectives will they offer?

The speakers in this session, representing a broad swath of institutions including academia, clinical trial specialists, representatives from industry, and the U.S. Food and Drug Administration (FDA), are as follows:

  • Sumithra J Mandrekar, PhD, Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN
  • Laurie H. Sehn, MD, British Columbia Cancer Agency, Vancouver, BC, Canada
  • Ann T. Farrell, MD, U.S. Food and Drug Administration, Bethesda, MD
  • Stephanie Seremetis, MD, Novo Nordisk A/S, Plainsboro, NJ

Everyone will analyze, as a case study, a couple of recent drug approvals. We will also discuss how to move forward so that all constituencies can agree on how to achieve the goal of getting drugs to pass as quickly and as safely as possible.

Discuss the new trial designs that will be covered in this session – why were they implemented?

Granting accelerated approval to investigational agents based on results from single-arm studies could lead to the approval of a lot of new agents. What has also become more common, and we will give examples during the session, is the concept of using a “synthetic control” arm. With this design, researchers collect data on patients being treated in practice – so-called real-world data – to match the characteristics of patients being treated in the context of a clinical trial. This approach was used with the approval of tafasitamab plus lenalidomide for DLBCL. Investigators could not have developed a good conventional control arm because of the effects of lenalidomide alone in that population. This is a new trend and practicing physicians need to understand how to interpret these data and what the limitations are.

What do you think attendees will learn from this session?

I hope people come away from this session with continued enthusiasm over the current era of riches in terms of new drug development. I want people to have a better understanding about how the FDA views these types of “synthetic control” trials and how the agency expects clinicians to use these approved drugs – appreciating that the decision was based on far fewer data than what would have been collected with a full approval from a phase III trial.