The FDA Oncology Center of Excellence and the Office of Oncologic Diseases is requesting that applicants submitting data in support of NDA/BLAs voluntarily add flags to datasets to discriminate between REMOTE assessments and TRIAL SITE assessments. The intent is to allow FDA’s Oncology Center to learn from trials conducted in the COVID-19 pandemic that permitted some aspects of trial conduct to be performed remote from trial sites to reduce potential COVID-19 exposure. FDA hopes to learn more about the opportunities and challenges of these REMOTE modifications to foster use of “decentralized” aspects of clinical trials prospectively in the post-COVID era.

Background 

• Decentralized Clinical Trials (DCT) may have several potential benefits including reduced patient and sponsor burden and increased accrual and retention of a more diverse trial population. 
• Use of full or hybrid DCT designs by commercial sponsors has been rare in oncology, in part due to uncertainty surrounding the effect of remote assessments on data quality and outcomes.
• COVID-19 has necessitated DCT-type trial modifications such as remote assessments to reduce patient exposure to COVID-19 infection from travel to trial sites. 
• Many of these remote assessment modifications were deployed in the middle of large ongoing cancer trials. 
• There is an opportunity to evaluate the effect of remote assessments on trial data to advance Decentralized Trials in oncology.
• Better understanding of the effect of DCT modifications can reduce uncertainty for sponsors and regulatory bodies, and identify mitigation strategies for future prospective DCT designs. 

Issue

There is currently no standard approach to how COVID-19 modifications are/will be identified in clinical trial datasets submitted to FDA.

A standardized COVID-19 trial modification dataset to clarify which remote modifications were permitted, and flags in existing SDMT and ADAM datasets to discriminate REMOTE from TRIAL SITE assessments, can assist FDA and sponsors in regulatory science research to characterize types of remote assessments deployed in cancer trials and their potential impacts on trial data when compared to central (trial site) assessments. This research can facilitate the advancement of decentralized trials in the post-COVID era leading to efficiencies and advantages to patients and sponsors alike.

Key REMOTE assessments/trial conduct of Interest:

1. Remote clinic visits (telemedicine)
2. Remote labs
3. Remote imaging
4. Remote administration of IP
5. Remote site monitoring

*For the purposes of this document, “REMOTE” is considered obtaining the assessment at a location outside of the standard clinical trial site assessment location noted in the initial protocol. “TRIAL SITE” is considered the location of clinics, laboratory and imaging facilities local to the investigator site. 

To facilitate the ability for FDA to understand the key REMOTE trial modifications permitted in the trial, applicants are being asked to provide the following as part of submitted datasets:

1.    Creation of a COVIDMOD dataset that will document the timing of when REMOTE trial modifications to address COVID19 were permitted at the patient and site level.

Dataset Name- COVIDMOD 
 [PatientID], [Site], [ModType], [DateModStart], [DateModStop] 

Purpose: Document the date that remote assessments were permitted at the patient and site level.

Standardize 6 categories of [ModType] = Telemedicine visits, Remote labs, Remote imaging, Remote administration of investigational product (IP), Remote site monitoring, Other.

Note: Many trials may not have mandated remote assessments, rather began to permit on-site assessments to be done remotely as an alternative option. In these cases, it would still be useful to know the timing at which the remote assessment OPTION was permitted.

2.    Flag individual assessments (clinic visits, laboratory assessments, imaging assessments, delivery of IP) as to whether they were conducted REMOTE or at the standard trial site.

Flag individual assessments that were conducted REMOTE rather than at the standard trial site. One option is to create a separate column in the ADAE, ADLB, ADRS, and ADEX that will allow FDA to identify assessments/procedures that were conducted remotely.

This may be implemented through use of a SUPPSV dataset that would be linked to the SDTM dataset, SV (study visit). The SUPPSV dataset should include one row each to get additional details on the conduct of the following assessments: laboratory (REMOTE vs TRIAL SITE), imaging (REMOTE vs TRIAL SITE), AE assessment (telemedicine or in-person), drug administration (REMOTE vs TRIAL SITE). The information captured in the SUPPSV dataset would then be used to populate all rows in the ADAE, ADLB, ADRS, and ADEX datasets.

Purpose: Allow FDA to identify each key trial assessment (clinic visit, laboratory, imaging, drug disposition) as REMOTE or TRIAL SITE

Note: 
While trial datasets may already be identifying REMOTE modifications as protocol deviations, we would like all REMOTE assessments to be flagged, rather than only those assessments that result in protocol deviations, given that once a trial protocol is amended to allow remote assessments they will no longer be considered Protocol Deviations.

3.    Flag imaging and laboratory assessments for data quality including [Missing? Y/N], [OutofWindow? Y/N], [UninterpretableScan Y/N]

Purpose: Allow an ability to determine whether remote assessment of laboratory or imaging affects data quality.

Examples of Potential Research Questions to Explore

Comparison of data from TRIAL SITE assessments versus REMOTE assessments

Example Research Questions:

What is the effect of allowing for REMOTE Laboratory Assessments?
     -    Compare missing data rates, out of window rates
     -    Compare dose mod rate, AE/SAE rate

What is the effect of allowing for REMOTE Imaging Assessments?
     -    Compare missing data rates, out of window rates
     -    Compare scan quality (interpretable vs uninterpretable)

What is the effect of Telemedicine replacing in person follow up clinic visits?
     -    Compare missed visits, out of window visits
     -    Compare dose mod rate, AE/SAE rate, hospitalization rate

What is the effect of allowing REMOTE investigational product (IP) administration? 
     -    Compare missed doses, dose modifications

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