Trial Approvals Face Delays During COVID-19 Pandemic

The authors of a study published in Trials said that many multicountry COVID-19 trials were quickly conceptualized without influencing the treatment guidelines. In the COPCOV trial (NCT04303507), investigators aimed to determine the efficacy of hydroxychloroquine and chloroquine as a prophylaxis for COVID-19. However, the trial faced delays and other challenges. In the current study, investigators aimed to analyze the bureaucratic challenges researchers faced when seeking multicountry trial approval.¹

“Not all health emergencies are best served through multicountry clinical trials, but international collaborative trials can be critical for reacting to unknown global transmission patterns and ensuring sufficient recruitment numbers, especially for outbreaks with relatively low attack rates,” the investigators said.¹

They found that the trial approval challenges come from a combination of conservative clinical practice interpretation as well as insufficient international guidance and leadership. They stated that this “contribute[s] to a dangerous ‘risk of therapeutic inertia’ in developing evidence during public health emergencies.¹

The COPCOV study was a trial for the repurposed drug hydroxychloroquine/chloroquine for use against COVID-19, which showed laboratory data that suggested activity in SARS-CoV-2. The trial was a double-blind, randomized, placebo-controlled trial conducted in health care settings and other facilities. Patients included were health care workers and other patients who were at risk of contracting COVID-19 and were followed for 5 months.^1,2

The goal was to recruit 40,000 patients in 50 to 100 sites across multiple countries. Treatment was randomized as either chloroquine or the placebo or hydroxychloroquine or the placebo. A loading dose was included, followed by daily doses for 3 months. The trial was launched around the same time the World Health Organization declared COVID-19 a public health emergency, and in mid-March 2020, investigators began the first steps for trial approvals in the United Kingdom, Italy, and Thailand.^1,2

As part of the current study, investigators quantitatively and qualitatively examine the challenges of trial approvals across multiple countries during health emergencies. The data were compiled from documents from the COPCOV trial between March 2020 and January 2022. Investigators also supplemented the data with interviews of 65 trial stakeholders conducted from April 2022 to September 2023.¹

For the qualitative results, investigators found that the initial researchers of the COPCOV trial contacted 76 countries, but only 11 recruited participants. Further, the protocol was submitted to 22 local ethics committees (ECs) and institutional review boards, 19 national ECs, and 14 national regulatory authorities. They also found that the median time for an initial decision was 104 days, with the initial protocol being under consideration for 3886 aggregated days in all participating countries. Countries with expedited review systems did process decisions faster at a median of 91 days compared to those without at a median of 122 days.¹

Even though submissions in 7 countries began in early May 2020, only the UK and Thailand were approved in time to begin to recruit during the first wave of the COVID-19 pandemic. Even though the African Vaccines Regulatory Forum advertised a 10-day emergency review goal, it took a minimum of 50 days for a decision for COPCOV and 164 days to begin recruitment.¹

As for qualitative findings, the primary barrier was the overlap in comments between ECs and national drug regulatory authorities along with duplicative roles. Trial approvals were also heavily influenced by external factors, and ECs and national drug regulatory authorities continued to cite a retracted paper for 2 years post-retraction. Many of the systems also remained maladaptive to the COVID-19 pandemic and required hard copies of documents and in-person notarization, which delayed submission.¹

“Overall, approvals for COPCOV took too long to provide urgently needed evidence in an unprecedented global medical emergency,” the study authors concluded.¹ “This evidence would have been most useful before the arrival of vaccines and thus missed the opportunity to inform therapeutic guidelines in the two years it took most of the world to be vaccinated.”

READ MORE: COVID-19 Resource Center

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REFERENCES

1. Winters J, Schilling WH. Approval delays in multi-country COVID-19 trials: the case of COPCOV and the risk of therapeutic inertia. Trials. Published online December 16, 2025. doi:10.1186/s13063-025-09300-z

2. Chloroquine/hydroxychloroquine prevention of coronavirus disease (COVID-19) in the healthcare setting (COPCOV). ClinicalTrials.gov identification: NCT04303507. Updated April 4, 2023. Accessed December 17, 2025. https://clinicaltrials.gov/study/NCT04303507