A longitudinal cohort study comparing clinical trials registered on ClinicalTrials.gov that stopped during the first three years of the SARS-CoV-2 pandemic with trials that stopped in the three years prior

Background

The global SARS-CoV-2 pandemic disrupted healthcare systems worldwide, raising concerns about its impact on clinical research. Early reports suggested reductions in participant enrollment, interruptions to ongoing trials, and challenges to protocol adherence, yet the magnitude and duration of these operational disruptions remain unclear.

Methods

We conducted a registry-based analysis comparing clinical trials during the COVID-19 pandemic (December 2019 to November 2022) with a matched pre-pandemic cohort (December 2016 to November 2019). Studies were included if they reported any modifications to trial status, enrollment, or protocols during the study periods. Key variables included trial stoppage, enrollment changes, and adoption of remote or hybrid procedures.

Results

The global SARS-CoV-2 pandemic resulted in widespread disruptions to trial operations with 13,323 clinical trials terminated, suspended or withdrawn over the course of the pandemic, a 38% increase compared to the 9,665 trials that stopped in the 3 years prior to the pandemic. Registries indicated a sharp decline in new participant enrollment across geographic regions and therapeutic areas, with partial recovery in later months. Review findings highlighted barriers including patient inaccessibility, staff redeployment, and supply chain interruptions.

Conclusions

The pandemic caused system-wide operational shocks that compromised trial timelines and may have downstream methodological consequences. Recovery in enrollment does not imply restoration of pre-pandemic protocol fidelity or outcome ascertainment. Standardized reporting of disruptions, proactive contingency planning, and resilient trial designs are needed to maintain data integrity during large-scale disruptions and to support reliable evidence generation.

What is new

• COVID-19 caused widespread, measurable disruptions to ongoing clinical trials globally, including pauses in enrollment, randomization, and follow-up.

• Recovery of trial activity was uneven across regions and therapeutic areas, with some trials still experiencing delayed recruitment and operational challenges months into the pandemic.

• Standardized reporting of trial disruptions and flexible, resilient trial designs are needed to maintain reliable evidence generation during future large-scale health emergencies.

Plain language summary

The COVID-19 pandemic affected the way clinical trials were conducted around the world. Many studies had to stop enrolling new participants, delay treatments, or change how patients were monitored. These interruptions were caused by travel restrictions, social distancing, and limited access to hospitals and research staff. Some studies used phone calls or video visits to continue collecting information, but these changes may have affected the quality of the results. Even as enrollment recovered in some areas, many trials still faced delays and challenges. Understanding these disruptions can help researchers plan better for future emergencies, ensuring that clinical trials remain safe, reliable, and useful for developing new treatments.