Our paper on identifying and mitigating biases in epidemiologic studies of #COVID-19 is now out and is #OA . doi.org/10.1007/s10654…. Skillfully led by
@AccorsiEmma
this project involved much of our group and many discussions arising from papers we were reading.
including @XuetingQ @EvaRumpler @LeeKShaffer @rebeccajk13 Ed Goldstein @NeneRiehus from @CCDD_HSPH with special guests @mats_julius and @mugecevik .
We consider the challenges of several kinds of studies: 1. Seroprevalence studies to estimate cumulative incidence
where a key challenge is representativeness of participants
and another (easier to adjust for) is imperfect test characteristics
2. Seroprotection studies (like this that just came out jamanetwork.com/journals/jamai… ) that seek to study the protection that prior infection or antibodies generated by it gives vs. future infection
Here key challenges are confounding (because the exposure and the outcome are both SARS-CoV-2 infection (or its consequence) just at different times -- so they share many common causes, as well as the issue of distinguishing direct from indirect effects
3. Risk factors for becoming infected. Here key challenges are selection biases of various sorts whereby those who are tested are at differential risk for infection from the source population
And differential misclassification because different kinds of tests are combined in one analysis, with different test characteristics, and different kinds of people tend to get different kinds of test. A risk factor for which test you get can look like a risk factor for infxn
For example different kinds of people get PCR vs serologic vs. antigen tests and the outcome is "any positive." Something similar is what makes interpretation of "any infection" in vaccine effectiveness studies tricky. (from a reply to another thread)
4. Secondary attack rate estimation eg in households. Lots of issues here. a) misclassifying index case (for example if the true index case is not the first to get sick in the hh)
b) misclassifying index when there are more than one but only one identified
c) misclassifying the contact type and infection status
d) misclassification of close contacts
We did our best to explain these sometimes subtle issues clearly (a large group of mixed backgrounds helped us, we think, ferret out unclarities) and offer practical solutions. We hope it will be useful to those (including ourselves) working on design and analysis of epi studies
Oh no! I was multitasking when I started this thread and left off coauthors @KeyaJoshi3 and @LeeKShaffer -- purely due to distraction - sorry! It was a great team effort.

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More from @mlipsitch

25 Feb
@ZoeMcLaren Thanks for tweeting about this article. I'm going to leave the matching issue for another day, but I want to add a note of caution as one of the authors. We did not claim, and the data do not directly address, the reduction in total infections.
@ZoeMcLaren We used the word "documented infection" to highlight the fact that many infections may have gone undocumented, especially those not symptomatic. The documented infections is a mixture of symptomatic (probably most of them) and asymptomatic (probably a smaller fraction)
@ZoeMcLaren As a consequence, it is mathematically possible to have a big effect on documented infections but a smaller effect on total infections. As an extreme case (likely more extreme than the truth) suppose that symptomatic infections are detected with probability 90% and
Read 6 tweets
31 Jan
@profshanecrotty Thanks @profshanecrotty for another super informative thread (ht @HelenBranswell for tweeting). My 2 cents is just to remember that the comparison between sero+ and sero- in the control arm in Novavax was not randomized and involved ~40 cases in each group.
@profshanecrotty @HelenBranswell Study was of course not designed to assess natural immunity, so kudos to the scientists for reporting these important data, but caution in interpretation. Several reasons to expect bias in observational seroprotection studies like this dash.harvard.edu/handle/1/37366…
@profshanecrotty @HelenBranswell In particular, those who got infected before (sero+) are likely still at high risk for subsequent infection(due to job, housing, use of transport, other persistent factors), leading to noncausal positive association betwn prior and future infection (confounding).
Read 4 tweets
31 Jan
Reupping this. Existing vaccines may well have been unable to get us to the herd immunity threshold before the variants made things harder. Now more unlikely. But if we can identify (hard) and vaccinate (harder) the most vulnerable it will make continued spread less destructive.
I haven't double-checked @roby_bhatt 's numbers but there is evidence so far that the vaccines are highly effective against the most severe forms of COVID, even in South Africa where most cases were the local variant.
Read 4 tweets
20 Dec 20
The @CDCgov ACIP move toward priortizing frontline workers is premised on "only slightly" more deaths compared to prioritizing by age &/or comorbidity. But that finding depends on the vaccine blocking transmission very efficiently, which we don't know.
In my opinion prioritizing by risk of death is the most robust strategy in the sense of being optimal or near-optimal whatever we find out about transmission blocking and the like. #ACIP
Notwithstanding misinterpretations and deliberate trolling from many the last few days, I have been saying for some time that in my view the most lifesaving strategy, and likely the one that will return us to functioning fastest, would be
Read 5 tweets
6 Dec 20
I'm quoted in this article as saying that prioritizing vaccines for teachers is not a way to reduce health inequities. Primary & secondary teachers are not the most disadvantaged in US - they have college degrees, middle-class salaries, health insurance. nytimes.com/2020/12/05/hea…
79% are white nces.ed.gov/programs/coe/i…. Those are facts. I support putting teachers above most other same-age adults because they perform a truly essential function in person that is much harder to perform remotely. Have said so publicly statnews.com/2020/12/02/how…
And was early to refer to them as essential workers nejm.org/doi/full/10.10… along with my coauthor and spouse @meiralevinson , who was a middle school teacher for 8y
Read 8 tweets
4 Dec 20
This is not a done deal but could happen (teachers would likely be in the same tier). If you object, make your views known to federal and state officials. States do not have to follow federal guidance, and if this is included in federal guidance, states should decline this part.
This is not animus against financial workers, and the industry is indeed essential, even if not all its activities are. The reason to prioritize many essential workers (grocery, transit) is that they are essential and THEREFORE highly exposed. Financial services much less so.
The goal of vaccinating essential workers in this instance should be to offer protection 2 those who can't work from home and are exposed to many other people in their workday, often with no or inadequate PPE. Teachers, grocery, transit are; financial svc can often work from home
Read 7 tweets

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