Lunch & Learn Workshop
May 17, 2022
Lunch and Learn at MassBio – Cambridge, MA
Join our speakers to learn on:
Evolution of Thinking about Endpoints in Oncology Clinical Trial
Monitoring of Late-Phase Oncology Trials
May 17, 2022 – 11:45 am – 2:45 pm EDT
MassBioHub – CAMBRIDGE, MA
11:45 am-12:00 pm : Registration
12:00-12:45 pm : Lunch
12:45-1:40 pm : Evolution of Thinking about Endpoints in Oncology Clinical Trials | Meredith M. Regan, Sc.D., Dana-Farber Cancer Institute (DFCI), Harvard Medical School
1:40- 2:30 pm : Monitoring of late-phase oncology trials | Laurence Collette, PhD, IDDI
2:30-2:45 pm : Coffee
- EVOLUTION OF THINKING ABOUT ENDPOINTS IN ONCOLOGY TRIALS | 12:45 – 1:40 pm EDT
Meredith M. Regan, Sc.D., Dana-Farber Cancer Institute (DFCI), Harvard Medical School
In later-phase oncology clinical trials, overall survival is classically considered to be the gold-standard endpoint, as we aim to cure or lengthen the survival of cancer patients. As therapies have evolved from cytotoxic to targeted and immune-based, so too has our thinking about clinical trial endpoints. There is renewed focus on demonstrating classical efficacy endpoints as valid surrogates for overall survival, and on proposing new efficacy endpoints tailored to the specific setting. As well, the statistical measures we estimate are discussed with greater emphasis of their clinical interpretation and the clinically-meaningful treatment effect. Toxicity and adverse event endpoints are receiving renewed attention, and integration of efficacy and toxicity endpoints are being considered. A prime example we’ll discuss is the unique patterns of anti-tumor response to immune checkpoint inhibitors, including the potential for durable disease control off treatment but also the potential for prolonged or late side effects of treatment, which has led to the proposal of a novel outcome measure to more comprehensively capture these patterns.
- As oncology therapeutics evolve, so too should our thinking about the endpoints to capture clinically-relevant features of these therapies, as complementary to overall survival
- As novel therapeutics prolong survival of patients diagnosed with advanced cancers, outcome measures should also focus on how that overall survival time is spent, considering durable clinical benefit but also toxicity of therapy
- Novel measures should comprehensively characterize all patients treated, and avoid over-emphasis of selected subsets of patients
- MONITORING OF LATE-PHASE ONCOLOGY TRIALS | 1:40 – 2:20 pm EDT
Laurence Collette, PhD, IDDI
Late-phase oncology clinical trials take a considerable time to complete due to the nature of the clinically relevant endpoints they aim to evaluate. Power considerations for such studies are typically based on a set number of events to be observed, or on similar requirements related to the total follow-up duration. Further assumptions are made regarding the expected outcome pattern in the reference study group, the treatment-effect pattern, the expected accrual rates as well as additional assumptions about the prevalence of targeted subgroups of interest and about censoring pattern for composite primary endpoints. Deviations from the design assumptions carry the risk that a trial might eventually not be able to reliably address the question of interest or may not do so in a timely manner. We will discuss such risks and how implementation of periodic blinded data reviews to monitor these key factors enables the identification of issues and, when needed, implementation of corrective measures.
Another key component of trial monitoring consists in monitoring the safety risks to participants through periodic unblinded review of the (unblinded) data of the entire study by a dedicated Independent Data Monitoring Committee. We will also discuss how to plan efficient interim monitoring of treatment effects in trials of immunotherapies and in targeted-treatment studies and how surrogate endpoints may or may not be used for such purpose. We will also review the key requirements to ensure that such reviews do not jeopardize trial integrity.
- The planning of oncology studies relies on a large number of assumptions. Adequate monitoring of these assumptions can identify issues and enable implementation of corrective measures.
- Trials become increasingly complex. Unblinded interim monitoring by a dedicated independent committee can ensure the risk-benefit balance to patients is preserved and that trials are made efficient. However, inadequate interim monitoring plan carry serious risks of making badly-informed decisions.
- Use of surrogate endpoints in early treatment decisions requires careful evaluation of their capacity to predict (lack of) treatment benefit.
Meredith M. Regan, Sc.D., is Associate Professor, Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute (DFCI) and Associate Professor of Medicine, Harvard Medical School.
- Dr. Regan is Director of the Statistical and Data Management Center for the International Breast Cancer Study Group, a cooperative clinical trials network centered in Bern, Switzerland.
- Her research includes clinical and translational studies to inform patient care and treatment selection for breast and genitourinary cancers, and the development and validation of clinical trial endpoints.
Laurence Collette, PhD, is Principal Statistician at the Consulting and Research Department of International Drug Development Institute (IDDI), where she advises small- and medium-size pharmaceutical and biotech companies on their drug-development program.
- Before joining IDDI in January 2021, Dr. Collette worked 25 years with the European Organization for Research and Treatment of Cancer (EORTC), where she was Director of the Statistics Department.
- Her research includes large real-world evidence studies and clinical studies to inform the clinical management of patients with testicular cancer and prostate cancer. She has a special interest in adaptive designs and in interim monitoring of later-phase studies that can maximize trial efficiency whilst optimizing their risk-benefit to the participating patients.
11:45-12:00 pm : Delegates Registration
12:00-1:45 pm : Lunch – Presentation IDDI and the speakers
12:45-1:30 pm : Evolution of Thinking about Endpoints in Oncology Clinical Trials – Meredith M. Regan, Sc.D.
1:30-1:40 pm : Q&A
1:40-2:20 pm : Monitoring of late-phase oncology trials – Laurence Collette, PhD, IDDI
2:20-2:30 pm : Q&A
2:30-2:45 pm : Coffee
We look forward to welcoming you !
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