Background 

In 2020, the US Food and Drug Administration issued guidance for trial investigators on clinical trial conduct for the duration of the COVID-19 public health emergency. This guidance clarified that, where appropriate, FDA regulations can accommodate the adoption of methods to facilitate trial decentralization through the remote collection of trial data outside of a standard in-person clinical trial site. These methods include patient-centric trial flexibilities such as electronic informed consent, virtual clinic visits, delivery of investigational product to the home and obtaining laboratory or imaging assessments locally. 

The FDA Oncology Center of Excellence (OCE) supports efforts to modernize clinical trials and evidence generation. COVID-19 provided a proof of concept for several decentralized trial modifications, and OCE is engaging with stakeholders to evaluate the benefits and challenges seen with decentralized trials in order to prioritize streamlined procedures to deploy in future prospectively designed cancer clinical trials

Why is This Important?

• Decentralized Clinical Trials (DCT) hold promise to reduce patient and sponsor burden and increase accrual and retention of a more diverse trial population, a key goal for OCE programs including Project Equity and Project Silver. 
• Evaluating the COVID-19 experience with remote assessments is important to develop best practices when deploying DCT modifications in future prospective DCT designs.

Ongoing Initiatives

The Clinical Trials Transformation Initiative (CTTI) Collaboration  

• There is a lack of data as to which DCT modifications were used in registrational trials conducted during the COVID-19 pandemic that subsequently were submitted and led to FDA approval of a new oncology indication. 
• FDA OCE has partnered with the Clinical Trials Transformation Initiative (CTTI) to conduct sponsor surveys to understand the prevalence of remote trial modifications for trials that provided evidence supporting the approval of supplemental or new drug or biologic applications for oncology indications. 

ASCO - Friends of Cancer Research Protocol Adherence and Fidelity Project

• Currently there isn’t a quantitative or qualitative analysis of the impact of COVID-era protocol deviations on clinical trial data from multiple sponsors. 
• Using a mixed methods approach (sponsor survey, interviews, and data meta-analysis), the project aims to describe and evaluate the impact of the COVID-19 pandemic on the types, frequency, and risk of protocol deviations documented in cancer treatment trials.
• FDA’s OCE is providing oncology regulatory perspective as a member of this working group.

FDA Guidance Document

• FDA Draft Guidance on Decentralized Clinical Trials for Drugs, Biological Products, and Devices (May 2023) 
• FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency (August 2021)

Select Publications

• Flaherty KT, Doroshow JH, Galbraith S, Ribas A, Kluetz PG, Pazdur R, Theoret MR. Rethinking Cancer Clinical Trial Conduct Induced by COVID-19: An Academic Center, Industry, Government, and Regulatory Agency Perspective. Cancer Discov. 2021 Aug;11(8):1881-1885 
• Rivera DR, Kluetz PG, Abdallah K, Agrawal S, Angus DC, Califf RM, Garrett-Mayer E, Hyer R, Lowy DR, Khleif SN. Clinical Evidence Generation During a Pandemic: Lessons Learned for Sustaining Progress. Cancer J. 2022 Mar-Apr 01;28(2):151-156 
• Friends of Cancer Research White Paper. Applying Learnings from Covid-19 to Advance Clinical Trial Conduct. Friends of Cancer Research Annual Meeting 2022

For Further Information

• Office of Oncologic Diseases (OOD)
• OOD Divisions and Contact Information
• Information for Sponsors: Submissions to the Office of Oncologic Diseases (OOD)
• Real-Time Oncology Review Pilot Program
• Oncology Regulatory Affairs