Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19 | NEJM – nejm.org

To the Editor

O’Brien et al. report that the combination of casirivimab and imdevimab (REGEN-COV) reduced the risk of symptomatic Covid-19 by 81.4% among persons exposed to SARS-CoV-2.1 However, we question the decision to communicate the effect size almost exclusively with the use of the relative risk reduction, calculated as 1 minus the relative risk. The authors placed a strong emphasis on the relative risk reduction for both primary and secondary efficacy end points throughout the abstract and main text but did not provide a complementary, absolute measure.

The Consolidated Standards of Reporting Trials guidelines recommend reporting both the absolute risk reduction and the relative risk reduction to fully describe the effectiveness of an intervention, as applied in many trials, including the recent trial of bamlanivimab–etesevimab combination for Covid-19.2 This practice is imperative, because the same relative risk reduction may represent very different absolute risk reductions — a relative risk reduction of 80% corresponds with an absolute risk reduction of 40% when the absolute risk decreases from 50% to 10% but with an absolute risk reduction of less than 1% when the absolute risk decreases from 1% to 0.2%. The provision of only the relative risk measure may lead clinicians, patients, and laypeople to overestimate treatment efficacy.3-5

Tomer Merison, Ph.D.
Shamir Medical Center, Tzrifin, Israel

Adam Goldman, M.D., M.P.H.
David Bomze, M.D., M.P.H.
Tel-Aviv University, Tel-Aviv, Israel

No potential conflict of interest relevant to this letter was reported.

This letter was published on October 6, 2021, at NEJM.org.

  1. 1. O’Brien MP, Forleo-Neto E, Musser BJ, et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med 2021;385:11841195.

  2. 2. Dougan M, Nirula A, Azizad M, et al. Bamlanivimab plus etesevimab in mild or moderate Covid-19. N Engl J Med 2021;385:13821392.

  3. 3. Malenka DJ, Baron JA, Johansen S, Wahrenberger JW, Ross JM. The framing effect of relative and absolute risk. J Gen Intern Med 1993;8:543548.

  4. 4. Bobbio M, Demichelis B, Giustetto G. Completeness of reporting trial results: effect on physicians’ willingness to prescribe. Lancet 1994;343:12091211.

  5. 5. Sorensen L, Gyrd-Hansen D, Kristiansen IS, Nexøe J, Nielsen JB. Laypersons’ understanding of relative risk reductions: randomised cross-sectional study. BMC Med Inform Decis Mak 2008;8:3131.

Response

The authors reply: We agree with Merison et al. that to fully describe the effectiveness of an intervention it is important to include both the relative risk reduction and the absolute risk associated with placebo and the intervention. In our article, we reported that REGEN-COV reduced the risk of symptomatic Covid-19 by 81.4% among persons exposed to SARS-CoV-2 and that the risk of Covid-19 was 1.5% (11 of 753 participants) in the REGEN-COV group and 7.8% (59 of 752 participants) in the placebo group. Hence, an absolute risk reduction of symptomatic Covid-19 infection of 6.3 percentage points (calculated as 7.8% minus 1.5%) was observed. For the other end points, summary results were reported in the article for each trial group, and the absolute difference can be calculated in a similar manner.

Meagan P. O’Brien, M.D.
Peijie Hou, Ph.D.
David M. Weinreich, M.D.
Regeneron Pharmaceuticals, Tarrytown, NY

Since publication of their article, the authors report no further potential conflict of interest.

This letter was published on October 6, 2021, at NEJM.org.

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