Physician Views results: Lack of durability, emergence of serious side effects top doctors' concerns about COVID-19 vaccines

Feedback from 341 physicians (254 primary care practitioners and 87 infectious disease specialists) presents an optimistic outlook on the back of provisional COVID-19 vaccine data. Nearly half anticipate a return to the 'old normal' by the end of 2021.

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Please note: this poll was run in response to interim data for Pfizer and BioNTech's vaccine (more here), which was shown to be more than 90% effective, but before Monday's announcement from Moderna confirming interim analysis data showing 94.5% effectiveness (more here).

Pfizer and BioNTech announced interim efficacy data for their mRNA COVID-19 vaccine candidate BNT162b2 last week, showing it to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim analysis.

The analysis evaluated 94 confirmed cases of COVID-19 in trial participants, from a study with 43,538 enrolees. The case split between vaccinated individuals and those who received the placebo indicated a vaccine efficacy rate above 90%, at seven days after the second dose. This means that protection is achieved 28 days after the initiation of the vaccination, which consists of two doses. Pfizer has said it is likely that people will require "periodical vaccinations,” and no serious safety concerns have been observed.

Unsurprisingly, given the circumstances of the COVID-19 pandemic, the speed at which initial vaccines have been developed and a widely shared view from experts that vaccines with 60-70% effectiveness would have represented a notable breakthrough, the feedback from physicians we gained through our snap-poll is overwhelmingly positive.

This sentiment will have been strengthened by yesterday's confirmation of a positive readout for a second COVID-19 vaccine using similar technology. Indeed, Moderna's candidate (mRNA-1273) may be even more effective, but it is the accumulated data for two candidates that both demonstrate 90%-plus effectiveness (albeit after the first interim analysis) that is most compelling.

To this end, Pfizer's decision to delay its first interim analysis until more events accrued (94 versus the initially planned 32; Moderna's study had accrued 95 events) has ultimately played an important role in building confidence in the outlook for first-generation (and mRNA) vaccines. A view that is shared by the medical professionals tasked with overseeing future deployment.

If the bar has been set high by both BNT162b2 and mRNA-1273, it remains to be seen if the effectiveness of these vaccines changes (and potentially decreases) as the respective clinical studies evaluating them continue through to final analysis. Other vaccines in development may also be shown to work, but with effectiveness rates lower than 90%.

On average, respondents to our poll said that in light of the initial data for Pfizer and BioNTech's vaccine they would start to question the rationale for using it if its effectiveness dropped below 70%. This could also represent an important benchmark for readouts of other vaccines, as demand will ultimately require the supply of multiple products (at 70% it is also in-line with what was the widely expected effectiveness of first-generation vaccines and notably above the 50% effectiveness required by the FDA to consider approval).

In terms of their biggest outstanding concerns about COVID-19 vaccines, physicians cite the subsequent emergence of serious side effects and lack of durability (i.e. effectiveness that lasts less than a year) as the biggest potential issues (both cited by 21% of respondents).

Logistical challenges (cited by 15% of physicians) and a current lack of evidence demonstrating effectiveness in preventing severe COVID-19 (10%) also feature prominently as issues of note. However, the new data presented yesterday by Moderna go some way to ease these concerns: mRNA-1273 does not require storage at below -80C (like BNT162b2) and can be refrigerated for 30 days; and initial Phase III data also show 11 severe COVID-19 cases in the placebo arm of the study and none in the vaccine arm.

Readout of better-than-expected initial data for two of the most advanced COVID-19 vaccine candidates is fuelling expert opinion that the acute phase of the COVID-19 pandemic will end next year, a view shared by just under half of the physicians we polled. Another third of respondents believe vaccines will prompt a return to the 'old normal' by mid-2022 at the latest.

To read more Physician Views Poll Results articles, click here.