AstraZeneca to release further data on COVID-19 vaccine amid DSMB concerns

AstraZeneca said Tuesday that it will release results from the primary analysis of the Phase III D8110C00001 trial of its COVID-19 vaccine AZD1222 following concerns raised by the data and safety monitoring board (DSMB) over recently announced interim findings. The company indicated that it will provide the most up to date efficacy data within 48 hours.

On Monday, AstraZeneca reported interim results from the study, with AZD1222 demonstrating efficacy of 79% at preventing symptomatic COVID-19, with comparable benefit seen across ethnicity and age, while having an efficacy rate of 80% among those aged 65 years and over. Data also showed that the vaccine was 100% effective at preventing severe disease and hospitalisation.

Most favourable data chosen

However, hours later, the US National Institute of Allergy and Infectious Diseases (NIAID), which provided funding for the study, issued a statement related to concerns raised by the DSMB about the completeness of the data. According to NIAID, the DSMB suggested that AstraZeneca included "outdated information" when initially disclosing the results, which may have provided an incomplete view of the efficacy data.

According to The Washington Post, the DSMB wrote a letter to AstraZeneca and the other trial sponsors citing concerns that the UK drugmaker "chose to release...the most favourable" data, rather than the most recent and complete data. "Decisions like this are what erode public trust in the scientific process," the DSMB wrote, adding that during meetings with AstraZeneca in February and March, the effectivness of AZD1222 at preventing symptomatic COVID-19 was between 69% and 74%. The DSMB "strongly recommended" that these results should be included in AstraZeneca's reporting of the interim findings.

"Unforced error" by AstraZeneca

Anthony Fauci, NIAID director, remarked that although AZD1222 is "likely a very good vaccine," the DSMB "got concerned" that the data in AstraZeneca's public statement "might, in fact, be misleading a bit." Fauci said "I was sort of stunned. We felt that we could not remain silent. In my mind, it's an unforced error by the company." Fauci continued "this sort of thing does nothing but cloud the picture. I don't think it reflects on the vaccine. I think it reflects on how the data has rolled out."

At the time the results were released, Mene Pangalos, executive vice president of biopharmaceuticals R&D at AstraZeneca, noted that at the interim analysis, there were five cases of severe disease in the placebo group, versus none in those given AZD1222, although he conceded that more cases had accrued since this time.

Data cut-off of February 17

On Tuesday, AstraZeneca explained that the pre-specified interim analysis was based on a data cut-off of February 17. The company added that it has "reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis," whilst it is "now completing the validation of the statistical analysis."

NIAID urged AstraZeneca "to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible." The company said it "will immediately engage" with the DSMB to share the primary analysis with the most recent efficacy data.

For related analysis, see ViewPoints: AstraZeneca & Oxford silence the doubters.

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