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Date: November 25th, 2020

Guest Skeptic: Dr. Joe Vipond has worked as an emergency physician for twenty years, currently at the Rockyview General Hospital.  He is the President of the national charity Canadian Association of Physicians for the Environment (CAPE), as well as the co-founder and co-chair of the local non-profit the Calgary Climate Hub, and during COVID, the co-founder of Masks4Canada. Joe grew up in Calgary and continues to live there with his wife and two daughters.

Reference: Bundgaard et al. Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers: A Randomized Controlled Trial. Annals of Internal Medicine 2020

Case: : Alberta is the last province in Canada that has yet to enact a mandatory mask policy. Should they do it?

Mask4All Debate

Background: During a respiratory pandemic, there still remains substantial questions about the utility and risk of facial masks for prevention of viral transmission. We debated universal mandatory masking back in the spring on an SGEM Xtra episode.

Some very well known evidence-based medicine experts like Dr. Trisha Greenhalgh were advocating in favour of stricter mask regulations based on the precautionary principle (Greenhalgh et al BMJ 2020). She was challenged on her position (Martin et al BMJ 2020) and responded with an article called: Laying straw men to rest (Greenhalgh JECP 2020).

A limitation of science is the available evidence. SARS-CoV-2 is a novel virus and we did not have much information specifically about the efficacy of masks. We needed to extrapolate from previous research on masks and other respiratory illnesses.

However, we do have a firm understanding of the germ theory of disease and masks have been used for over 100 years as an infectious disease strategy. It was surgeons in the late 1890’s that began wearing masks in the operating theaters. There was skepticism back then as to the efficacy of a “surgical costume” (bonnet and mouth covering) to prevent disease and illness during surgery (Strasser and Schlich Lancet 2020).

There was one recent cluster randomized control trial  looking at surgical masks, cloth masks or a control group in healthcare workers (MacIntyre et al BMJ 2015). The main outcomes were clinical respiratory illness, influenza-like illness and laboratory-confirmed respiratory virus infection. All infectious outcomes were highest in the cloth mask group, lower in the control group and lowest in the medical mask group. As with all studies this one had limitations. One of the main ones is this looked at healthcare workers wearing a mask as protection not in the general public as a source control.

There has been a systematic review meta-analysis on physical distancing, face masks and eye protection to prevent SARS-Cov-2 (Chu et al Lancet 2020). With regards to masks, they found that face masks could result in a large reduction in risk of infection with a stronger association with N95 or similar respirators compared with disposable surgical masks or similar cloth masks.

SRMA also have limitations and one of the main ones is they are dependent on the quality of the included studies. This review in the Lancet included ten studies (n=2,647) with seven from China, eight looking at healthcare workers (not general public) and only one looking at COVID19. All 10 studies were observational designs and the authors correctly only claim associations. They also say their level of certainty about masks being associated with a decrease in disease is considered “low certainty” based on the GRADE category of evidence.

When considering an intervention, we cannot just consider the potential benefit, but we must also consider the potential harms. There is little or no evidence that wearing a face mask leads to potential harms. Yes, there are case reports of harm, children under 2 years of age should not wear face coverings (AAP News) and studies systematically under report adverse events (Hodkinson et al BMJ 2013) but the pre-test probability of individual harm is very low.

What many studies on masks conclude is we need better evidence to inform our decisions. Now we have the first published randomized control trial on mask wearing in public to prevent transmission of COVID19.

Clinical Question: Does recommending surgical mask use outside the home reduces wearers’ risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures?

Reference: Bundgaard et al. Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers: A Randomized Controlled Trial. Annals of Internal Medicine 2020

  • Population: Danish adults > 18 years of age without symptoms associated with SARS-CoV-2 (or previously tested positive for SARS-CoV-2), working out-of-home with exposure to other people for more than three hours per day and who do not normally wear a face mask at work
    • Exclusions: 18 years of age and younger, previously tested positive for SARS-CoV-2 or wears a face mask at work
  • Intervention: Participants were encouraged to follow the authorities general COVID-19 precautions and to wear a surgical face mask for a 30-day period when out-of-home (50 surgical masks were provided)
  • Comparison: Participants were encouraged to follow the authorities general COVID-19 precautions and no face masks were provided and no face mask recommendation
  • Outcome:
    • Primary Outcome: SARS-CoV-2 infection at one month by either antibody testing (IgG and/or IgM), polymerase chain reaction (PCR), or hospital diagnosis.
    • Secondary Outcome: PCR positivity for other respiratory viruses
    • Tertiary Outcomes: Returned swabs, Psychological aspects of face mask wearing in the community, Cost-effectiveness analyses on the use of surgical face masks, Preference for self-conducted home swab vs. healthcare conducted swab at hospital or similar, Symptoms of COVID-19, Self-assessed compliance with health authority guideline on hygiene, Willingness to wear face masks in the future, Health care diagnosed COVID-19 or SARS-CoV-2 (antibodies and/or PCR), mortality as with COVID-19 and all-cause mortality, Presence of bacteria; Mycoplasma pneumonia, Haemophilia influenza and Legionella pneumophila (to be obtained from registries when made available), Frequency of infected house-hold members between the two groups, Frequency of sick-leave between the two groups (to be obtained from registries when made available), and Predictors of primary outcome or its components

Authors’ Conclusions: “The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection.”

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. No
  2. The patients were adequately randomized. Yes
  3. The randomization process was concealed. Yes
  4. The patients were analyzed in the groups to which they were randomized. Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). No
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Unsure
  11. The treatment effect was large enough and precise enough to be clinically significant. Unsure

Key Results: The trial included 6,024 people with mean age of 47 years and almost 2/3 identified as female.

No statistical difference in SARS-CoV-2 infection between the mask group and no mask group

  • Primary Outcome: SARS-Cov-2 infection (Intension-to-Treat)
    • 1.8% mask group vs. 2.1% no mask group
    • − 0.3 percentage point (95% CI, −1.2 to 0.4) P= 0.38
    • Odds Ratio (OR) 0.82 (95% CI, 0.54 to 1.23) P= 0.33
      • Per-Protocol Analysis: 1.8% mask group vs. 2.1% no mask group with absolute difference -0.4% (95% CI -1.2 to 0.5) P = 0.40 and OR 0.84 (95% CI, 0.55 to 1.26) P = 0.40
    • Secondary Outcomes: Other viral infection
      • 0.5% mask group vs. 0.6% no mask group

There are a number of nerdy points we could have discussed but in typical fashion and to keep the blog/podcast to a digestible length we have highlighted five.

1) Methods: Some questions have been raised about the methodology. This trial was registered with ClinicalTrials.gov (NCT04337541). The trial protocol was registered with the Danish Data Protection Agency (P-2020-311), adhered to the recommendations for trials described in the SPIRIT Checklist and they published their methodology in the Danish Medical Journal (Bundgaard et al 2020).

Some of the comments about the methodology specifically referenced the lack of ethics approval. However, the researchers presented the protocol to the independent regional scientific ethics committee of the Capital Region of Denmark, which did not require ethics approval in accordance with Danish legislation. The trial was also done in accordance with the principles of the Declaration of Helsinki.

In the supplemental material there is a letter from the Chairman of the Ethics Committee saying they do not require ethics approval. It is hard to be critical of the researchers who took reasonable steps to address ethical concerns and were told they did not need ethics approval.

“Taking a known test for a known disease is not a health science intervention – it must be regarded as pure clarification of whether one has the disease. The intervention in this project is therefore only that some of the subjects wear face mask. I mean that is such an insignificant intervention that the project is not subject to notification, cf. section of the Committee Act 1 piece. 4 and may be initiated without the permission of the Science Ethics Committees for the Capital Region.

Thus, there is no ethical stance in the refusal to assess the project or negative assessment of its content.”

2) Adherence: Only 46% of participants wore the mask as recommended. This would minimize any potential benefit of the intervention. However, an additional 47% of participants wore the mask predominantly as recommended. This gives a total of 93% with just 7% not wearing the mask as recommended. Reasons for not adhering to the mask recommendation at all times during the study period were due to wet masks (50%), work (32%) and unknown (18%). It would have been helpful if they collected data on mask wearing in the control group too.

Lack of adherence is certainly a limitation to this clustered randomized control trial. Expecting 100% compliance is unrealistic. We do have evidence that adherence to interventions is usually lower outside of a formal study. We also have to consider the external validity of this study population that do not traditionally wear masks to other societies that often wore masks in public before COVID19.

3) Outcome Measure: The primary outcome as a composite outcome to make the diagnosis of SARS-CoV-2. Most were made using the self-administered antibody test with fewer made using PCR and clinically diagnosed.  The self-administered part should affect both groups equally but could impact on the number of positive cases potentially biasing towards the null hypothesis.

We discussed the diagnostic accuracy of testing For COVID19 in the on SGEM#299 with Dr. Chris Carpenter and his systematic review meta-analysis on the topic published in AEM. This included a number of biases that could have impacted the results. Two important ones would be spectrum bias and imperfect gold standard. (Kohn et al 2013)

  • Spectrum Bias (Effect): Sensitivity depends on the spectrum of disease, while specificity depends on the spectrum of non-disease. Because the Danish population had a low prevalence of COVID19 this can make specificity (true negatives) look very good.

 

  • Imperfect Criterion Standard (Copper Standard Bias): This is what can happen if the “gold” standard is not that good of a test. We do not have a great test for diagnosing COVID19 and they used PCR which has a sensitivity (true positives) of 60-78%, antibody serology (sensitivity of 82-100% and specificity of 87-100%) and clinical diagnosis (which may have introduced incorporation bias)

There is also a concern about one month not being long enough to capture positive cases. Participants were asked to self-test at the beginning of the trial, end of the trial and if they became symptomatic. It can take up to two weeks to develop symptoms and the people in the first 14 days of the study could have been infected before the intervention of masks were introduced. Participants also could have got infected between day 14 and the end of the study and not tested positive using the antibody test. In addition, the antibody test that was used is no longer recommended by the FDA.

4) Asking the Wrong Question: Mask wearing in public is thought to be more for source control than personal protection. It is to prevent the mask wearer from giving SARS-CoV-2 to others more than preventing the wearing from catching the disease. Based on previous work, the pretest probability of finding a statistically or clinically significant impact on the wearer of a mask was very low.

We think they asked the wrong question. They asked: does public mask wearing in their Danish society protect the wearer from getting covid19? The answer is no. What we really want to know is the net impact of public mask wearing at a population level to prevent getting COVID19 and the all-cause morbidity and mortality? This trial cannot answer nor claimed to be able to answer this larger, more important question.

We don’t know from this trial design the impact on protecting others (source control) and external validity to other populations with different mask wearing practices. This trial just reports that public mask wearing does not statistically lower the odds of the mask wearer from getting COVID19 over a short time frame in a society with low prevalence of disease and low mask wearing in general. However, it doesn’t mean masks don’t work and this cannot be emphasized enough.

Randomized control trials can be very informative when done well. It is difficult to do an RCT at a population level looking at source control. Other sources of information can be used: anecdotes (hypothesis generating), population cohort studies, modelling to engineering studies.  These other lines of evidence predominately fall towards supporting mask wearing.

There is another randomized control trial out of Denmark with 66,000 participants looking at cloth mask use to prevent COVID19 like illnesses over four months. This study is ten times larger and is four times longer in duration. However, it is not anticipated to be completed until the summer of 2021.

5) Should it have Been Published? This is a larger scientific issue. We think for a variety of reasons that the trial should have been published. Publishing it opens the trial to a broader post-publication peer review. Experts can then challenge the study and point out the imitations and threats to the validity of the authors’ interpretation and conclusions.

Another reason is that we live in a world of that is susceptible to conspiracy thinking and social media. Not publishing the results could have fueled conspiracy theories about masks use.

Another very important reason is that people volunteered for this trial. A case could be made that all studies involving human volunteers should be published. There is an organization called All Trials that advocates that all trials past and present should be registered and their full methods and summary results be reported.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We disagree with the conclusions because we are unsure of the impact of mask wearing on the mask wear based on their study.

SGEM Bottom Line: We do not have high-quality evidence that public mask wearing prevents the wearer for getting COVID19. We need to be careful not to over interpret these results and incorrectly conclude public mask wearing does not work.

Case Resolution: Joe will continue to advocate for Alberta to enact a mandate for people to wear a mask in public.

Dr. Joe Vipond

Clinical Application: This clustered randomized control trial asked a very narrow question that makes it hard to apply clinically to the broader question of does public mask wearing lower the burden of COVID19 in the general population. It was reassuring that they did not see any signal of harm.

However, we still need to make recommendations based on the best evidence even if we don’t have high-quality evidence.

What Do I Tell the Patient (the Public)?  A.C.T. smart

 

Keener Kontest: Last weeks’ winner was David Michaleson. He knew the first Physician Assistant in the USA graduated from Duke University in 1967.

Listen to the SGEM podcast to hear this weeks’ question. Send your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Other FOAMed:

  • Medpage Today: Here’s How to Think About the Danish Mask Study
  • REBEL EM: The DANMASK-19 Trial: Masks Not Effective to Prevent COVID-19? Not So Fast!!!
  • EM Lit of Note: The Futility of Mask Wearing?
  • PulmCrit: Why the DANMASK Trial is a Futile Diversion – The Limitations of RCTs

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.