From the time the COVID-19 outbreak was declared a pandemic, the number of studies conducted around the world to either diagnose, prevent or treat the virus literally exploded (1570 as on today, according to the Cytel Global Coronavirus COVID-19 Clinical Trial Tracker1).
Moreover, the pandemic impacted the regular schedule of ongoing clinical trials. Health authorities such as the FDA, promptly provided recommendations in the form of questions and answers on how to handle “disruptions” due to the pandemic2. These disruptions include a range of challenges including skipped assessments or study withdrawal.
“CDISC launched a task force in an effort to support CDISC members and the research community as they work tirelessly to discover critical breakthroughs to treat COVID-19 …. The task force was launched with the goal of developing Interim User Guide and Related material” said David Bobbitt, CDISC CEO, in an interview with Outsourcing-Pharma.com3. On April 21, 2020, the task force released two guidances. In this blog, I provide you with a quick summary of what these guidances address.
The two guidances are:
- Guidance for Ongoing Studies Disrupted by COVID-19
- CDISC Interim User Guide for COVID-19
Continue reading to learn more.
Guidance for Ongoing Studies Disrupted by COVID-19
The focus of the first guidance, Guidance for Ongoing Studies Disrupted by COVID-19 Pandemic4, is to support sponsors in identifying possible issues during data collection. It provides recommendations on how to change the eCRF or how to record data to identify situations in which events like the current pandemic cause a study withdrawal. Similarly, when mapping data to SDTM, the guidance provides some recommendations on how to ensure the information or records affected by the pandemic are identified.
The guidance allows sponsors to choose from the options offered. For example, a sponsor can choose to treat a missed visit or a visit conducted remotely because of a lockdown situation, either as a protocol deviation (DV domain) or by using a new proposed VE (Visit Events) custom domain and some Non Standard Variables (NSV), to flag visits impacted by the pandemic.
The latter is the approach we chose for an ongoing study in agreement with our sponsor. The drawback of this approach is the need to amend eCRF, thus creating an ad hoc new form. However, we think this is the most “clean” approach given the fact that missed visits are not considered as protocol deviations. Moving forward, this new VE domain could be a good candidate for a new standard for storing information and reason about missed/skipped visits, as these visits are typically not mapped into SDTM standard SV domain.
In another event, for an occurred planned visit, an individual’s scheduled study assessment could have been skipped. For example, assume a planned visit that requires going to the hospital, seeing the doctor, getting the treatment, having the vital signs assessed, getting a blood test, etc. Now suppose the subject was able to go the hospital and have the planned visit to the doctor, but as the labs were closed due to the pandemic, the subject did not get the blood test done. In this case, for the data in the CRF, we need to find a way to identify planned “study events” such as the lab sample collection, that did not occur. The method suggested here is to use NSV, same as for the skipped visits mentioned above.
Other recommendations cover TS, DS and AE domains (see also MedDRA webinar5).
Additionally, the guidance introduced a second custom domain, ST – Subject Transfers, to store information about the new site to which the subject was transferred in the event that the site where the subject was initially enrolled was closed due to the pandemic.
CDISC Interim User Guide for COVID-19
The second guidance, CDISC Interim User Guide for COVID-196, provides recommendations and examples to support new studies on any COVID-19 related indication. It covers topics ranging from:
- collecting pre-existing medical conditions (MH domain) and other possible risk factors such as travel in the area with confirmed COVID-19 cases; or
- exposure to people; or
- facilities that could potentially increase the risk of developing COVID-19 infection (a new custom domain ER - Environmental and Social Factors).
The guidance also relates to specific laboratory tests to support diagnosis (LB) and identification of the virus (MB for antibody testing and SARS-CoV-2 Viral Load).
Other recommendations cover MH, CM, PR, VS, RE, CE, HO, QS and the custom domain QT, originally proposed by the QT Studies Therapeutic Area User Guide7.
The guidance also has a specific section for vaccines studies, highlighting some of the known issues from the Vaccines Therapeutic User Guide8.
Both two guidances do not provide any specific recommendation for CRF design or any specific topic related to the analysis of the data, for example, ADaM. A CDISC webinar providing more details is available on the CDISC website9.
- Cytel Global Coronavirus COVID-19 Clinical Trial Tracker) https://www.covid19-trials.com/?__hssc=114829016.1.1592150589783&__hstc=114829016.33caf778de5c943b5cefb42bbfaa9250.1559491715482.1592118026728.1592150589783.65&__hsfp=3057297023&hsCtaTracking=76d7ce2a-c00e-4e2c-b62b-d24f0b957746%7Ca7501ffd-8288-48d8-a35a-11ed53fb1576
- US Department of Health and Human Services, Food and Drug Administration. FDA guidance on conduct of clinical trials of medical products during COVID-19 pandemic. Guidance for industry, investigators, and institutional review boards. https://www.fda.gov/media/136238/download. Published March 2020. Updated April 2, 2020. Accessed April 9, 2020.
- CDISC launches COVID-19 research standards task force, https://www.outsourcing-pharma.com/Article/2020/04/30/CDISC-task-force-tackles-COVID-19-research-standards
- Guidance for Ongoing Studies Disrupted by COVID-19 Pandemic, April 2020 https://www.cdisc.org/standards/therapeutic-areas/covid-19/interim-user-guide-covid-19
- MedDRA COVID-19 terms webinar, April 2020 https://www.meddra.org/COVID-19-terms-and-MedDRA
- CDISC Interim User Guide for COVID-19, April 2020 https://www.cdisc.org/standards/therapeutic-areas/covid-19/interim-user-guide-covid-19
- QT Studies Therapeutic Area User Guide, https://www.cdisc.org/standards/therapeutic-areas/qt-studies
- Vaccines Therapeutic Area User Guide https://www.cdisc.org/standards/therapeutic-areas/vaccines
- CDISC COVID-19 User Guide Project Review Webinar, https://www.cdisc.org/events/webinar/covid-19-user-guide-project-review
About Angelo Tinazzi
Angelo Tinazzi is Senior Director, Statistical Programming, Clinical Data Standards and Clinical Data Submission at Cytel. He is a well- published and recognized expert in statistical programming with over 20 years' experience in clinical research. The application of CDISC standards in different therapeutic areas is part of his core expertise since 2003 in particular in the context of data submission to health authorities such as the FDA and PMDA.
Angelo is an authorized CDISC instructor and member of the CDISC ADaM Team as well as the CDISC European Committee where he also manages the Italian-speaking CDISC User Network.