Cancer Trials Should Focus On Collecting Data ‘Strictly Necessary’ For Assessing Efficacy
Executive Summary
In journal article, leaders from academia, industry, NCI and FDA propose building upon pandemic-necessitated flexibilities in clinical research, including making it easier for trial participants to access investigational drugs in their own communities and reduced reporting of uninformative adverse events.
Leaders in cancer drug development and regulation are calling for broader community- and home-based access to investigational drug products in clinical trials and reduced reporting of minor or uninformative adverse events on studies.
The recommendations are part of a push by researchers, industry and the Food and Drug Administration to extend and expand COVID-necessitated clinical trial flexibilities beyond the pandemic, creating a new standard for modern clinical trial conduct in the process.
In an article published in American Association for Cancer Research journal Cancer Discovery, seven representatives from academia, the National Cancer Institute, industry and the FDA’s Oncology Center of Excellence discuss positive changes in the conduct of cancer trials during the pandemic and how to make these changes permanent and build on them going forward. (See box for list of authors.)
“Rethinking Cancer Clinical Trial Conduct Induced By COVID-19: An Academic Center, Industry, Government and Regulatory Agency Perspective”
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Keith Flaherty – Massachusetts General Hospital director of clinical research
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James Doroshow – National Cancer Institute senior investigator
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Susan Galbraith – AstraZeneca executive VP of oncology R&D
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Antoni Ribas – University of California Los Angeles professor and AACR immediate past president
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Paul Kluetz – FDA OCE deputy director
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Richard Pazdur – FDA OCE director
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Marc Theoret – OCE deputy director
“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the article states.
“The COVID-19-induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing. But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” the authors said.
Mid-Trial Changes
In March 2020, as the impact of the SARS-CoV-2 virus’ spread across the globe became clear amid travel restrictions, quarantine requirements and supply chain interruptions, the FDA and other regulatory bodies began issuing guidance on flexible approaches to continuing clinical trials during the pandemic.
These included allowing for changes in how efficacy and safety assessments are conducted, how investigational drugs are distributed and where they may be administered. (Also see "Clinical Trial Sponsors Should Consider Changing Data Collection Amid COVID-19, US FDA Says" - Pink Sheet, 18 Mar, 2020.)
The FDA’s guidance has been updated numerous times since initial release. Among the topics it addresses are: remote visits, clinical outcome assessments and clinical site monitoring; electronic capture of informed consent; use of alternative sites for imaging assessments; and home delivery of low-risk investigational products. (Also see "US FDA Offers More Advice On Mid-Trial Changes For Pandemic-Impacted Studies" - Pink Sheet, 30 Mar, 2020.) (Also see "For COVID-Impacted Studies, US FDA Loosens Video Conferencing But Tightens Home Infusion Guidance" - Pink Sheet, 12 May, 2020.)
“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” lead author Keith Flaherty of Massachusetts General Hospital said. “This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials.”
The FDA’s OCE wants to leverage datasets from pandemic-interrupted trials to foster the use of decentralized approaches and has asked applicants to voluntarily flag assessments as having been conducted remotely or at a trial site. (Also see "US FDA Oncology Center Wants Trial Datasets Flagged As Remote Or In-Person Assessments" - Pink Sheet, 14 Apr, 2021.)
The authors believe some of the clinical trial flexibilities put in place to deal with COVID-19 not only should continue post-pandemic, but should be taken a step further because they will make it easier to participate in cancer trials and expand the reach of such studies beyond academic centers, especially to rural communities and underserved populations.
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Make electronic remote consenting permanent |
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Allow use of any laboratory or imaging center that meets specifications |
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Add patient-reported outcomes and telehealth approaches to routine clinical trial methodologies |
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Increased use of community-based network sites as opposed to clinical trial sites only |
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Direct-to-patient investigational product (oral drugs) and concomitant medication reporting via digital tools |
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Aspire to 100% remote infusions and monitoring when feasible based on a risk assessment |
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Decentralize clinical trial conduct and make it more accessible to rural areas and underserved populations; increase funding mechanisms for trials conducted in underserved communities; markedly broaden trials available for patients with wide range of comorbidities |
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Discuss mechanisms for use of clinical trial products obtained as commercially approved drugs |
Minimize Data Collection Burden
The authors also suggest additional process improvements and technology development aimed at making clinical trial participation more inclusive and less onerous, while still optimizing benefit-risk.
In the “new normal” for cancer trial conduct, there should be efforts to decrease collection of low-grade adverse events and minimize the effect of minor protocol deviations on study conduct, “rather than collect every recorded event irrespective of importance and relationship to the study endpoints,” the article states.
Similarly, the authors call for collecting “less low-value laboratory and clinical data per patient to minimize nonessential testing, instead of collecting all laboratory values despite not being related to the research being conducted.”
They also urge that the utility of new efficacy endpoints, such as time-to-event and PROs, be investigated as a means for decreasing cost and improving efficiency instead of relying exclusively on multiple specialized tumor measurements.
“In our current health context … every effort must be made to extend the cancer clinical research process further into the community setting, including provision of investigational intravenous therapeutics at the local level, reduction in reporting requirements for adverse events and low-value laboratory data in late-stage trials where these data are unlikely to have an adverse impact on patient safety, and use of patient-reported outcomes (PRO) as primary study endpoints,” the article states.
“Finally, all cancer clinical trials, including those supported by the NCI, would be dramatically streamlined by a national effort to make it possible to collect clinical trial data directly from a patient’s electronic health record.”