The National Institute of Allergy and Infectious Diseases (NIAID) has released a statement that the Data and Safety Monitoring Board (DSMB) expressed concern that AstraZeneca may have included outdated information from the US clinical trial, which may have provided an incomplete view of the efficacy data.
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:
“There is a single sentence behind this story:
‘The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.’
“I find this problematic in various ways. It reads like a sentence from the conclusions of a paper; but one that has been presented out of context, without any explanation of the reasons for drawing the conclusion, or of what they think the consequences might be.
“If you present data, stating the period in which the data were collected, how can the data be ‘outdated’. The AstraZeneca press release did say it was on ‘interim’ data. There may be more recent data; but that would not normally ‘outdate’ or invalidate the interim results.
“Note also the use of the subjunctive ‘may’, used twice in that sentence.
“In my opinion this is shamefully bad communication by NIH as with their lack of clarity they have left room for speculation which could be damaging for vaccine uptake.
“If asked to speculate about what underlies this, I would guess that they may be making the same points that I made in my earlier rapid response:
“One thing that is not clear in this press release is whether the study provided any information on the real-world efficacy of the vaccine against different variants of the virus. There is no information on whether genomic typing of the cases was undertaken, the prevalence of different variants in the study population, or the dates during which the data were collected (which would allow some inferences to be drawn on variant prevalence and thus vaccine efficacy against the variants). We know from other work that the vaccine seems to be highly effective against many variants, in particular, the more transmissible B.1.1.7 variant; but we do not know if the study will add to our knowledge on this.”
Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds, said:
“For me, this further announcement by the DSMB in response to the AZ release yesterday highlights the importance of data being provided at the same time as summaries being made public. Naturally, the news yesterday was taken in good faith and the issues raised by the DSMB may be a mere technicality, yet this won’t be clear until we have full disclosure. Nevertheless, we must ensure that issues such as this are dealt with appropriately and that idle speculation is not seized upon by groups seeking to undermine faith in vaccination programmes.”
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
“It is not unknown for a DSMB to disagree with investigators over interpretation of trial results.
“It is usually done in private, so this is unprecedented in my opinion.
“I have said frequently that ‘headline’ estimates of efficacy being compared between trials is very unreliable.
“The DSMB has responsibility essentially for safety of participants, not efficacy unless it is either so high or so low or negative that it is unethical to continue to randomise, so in some senses they might be seen to be exceeding their brief. If the protocol for an interim analysis gave a cut-off at a given number of events accrued, then AZ might be justified in sticking to that. However if AZ had not adhered to the protocol then obviously the DSMB are justified in raising the issue.
“One explanation might well be that this trial is currently being conducted when there is a large amount of a new variant about more recently, and, as might be expected, the efficacy against that variant might be less, so more recent data shows reduced efficacy. Of course the other vaccines may also show such reduced efficacy and we don’t know by how much.
“It does not leave me concerned particularly unless they had found a safety issue that was being hidden, which does not appear to be the case.”
Dr Peter English: “No conflict of interest to declare.”
Dr Stephen Griffin: “No conflicts.”
Prof Stephen Evans: “No conflicts of interest. I am funded (one day per week) by LSHTM. They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them. I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI. I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs. I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”