Drug companies are under pressure for more and more transparency in clinical trials. It has been a common practice now to post the clinical trial in clinicaltrials.gov before the first patient is enrolled in the study. However, the registration in clinicaltrials.gov includes not all details about the clinical trial. For example, the planned statistical analysis, the interim analysis, stopping rule,... are usually not part of the items to be published.
Transparency is also implemented after the clinical trial is completed. The clinical trial results need to be published in clinicaltrials.gov within one year of the last efficacy assessment. FDA is implementing a pilot program to encourage drug companies to post the clinical study report (CSR) and the statistical analysis plan (SAP). Some journal such as the New England Journal of Medicine (see an example) requires the study protocol and the SAP to be available as part of the supplemental material to the main publication.
It is rare to see the study protocol or SAP to be published while the clinical trial is still ongoing. But this happens now for COVID-19 vaccine clinical trials.
According to StatNews.com:
In an unprecedented show of transparency, the two frontrunners in the race to develop a Covid-19 vaccine released detailed protocols describing the studies testing their vaccines. The unusual step is part of an effort to proactively increase the public's trust in an eventual vaccine.
"This is an example of the comprehensive trial description that industry should be sharing," said Harlan Krumholz, a Yale cardiologist who has been a long-time advocate for increased transparency from drug companies.
The protocols are dense, and researchers will be poring over them in coming days. In both cases, there are plans for potentially stopping the studies early if the vaccines prove more effective than planned. Both protocols require that decision to be suggested by an independent Data Monitoring Committee, not by the companies. And in both cases, this committee reports directly to the company, not to academics who are running the study, something some experts say is disappointing.
The Moderna protocol can be found here "A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older"
The Pfizer protocol can be found here "A Phase 1/2/3, Placebo-Controlled, Randomized, Observer-Blind, Dose-Finding Study to Evaluate the Safety, Tolerability, Immunogenicity, and Efficacy of SARS-COV-2 RNA Vaccine Candidates Against COVID-19 in Healthy Individuals"AstraZeneca followed the suit and had just published its phase III study protocol. "A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 VectorVaccine, for the Prevention of COVID-19". See the article "AstraZeneca, Under Fire for Vaccine Safety, Releases Trial Blueprints"
The unprecedented move by three leading COVID-19 vaccine development companies is mainly driven by what happened in their phase III clinical trials. AstraZeneca's trial was paused for data monitoring committee review and then resumed; Pfizer's trial had its sample size increased from the planned 30,000 to 44,000 volunteers; Moderna's trial was slowed down in enrollment in order to ensure minority representation.
These phase III clinical trials for the COVID-19 vaccine are under the public's scrutiny for every move. It is understandable that the public demands transparency to see clinical trial protocols. For regular clinical trials under normal circumstances, it is still not the time for drug companies to make the study protocols public.