tetano
Editor, Senior Moderator
Int J Epidemiol
. 2026 Aug 18;55(5):dyag210.
doi: 10.1093/ije/dyag210.
Layan Sukik 1 , Pradipta Paul 1 , Houssein H Ayoub 2 , Peter Coyle 3 4 5 , Patrick Tang 6 , Mohammad R Hasan 7 , Hadi M Yassine 4 8 , Asmaa A Al Thani 4 8 , Zaina Al-Kanaani 3 , Einas Al-Kuwari 3 , Andrew Jeremijenko 3 , Anvar Hassan Kaleeckal 3 , Ali Nizar Latif 3 , Riyazuddin Mohammad Shaik 3 , Hanan F Abdul-Rahim 9 , Gheyath K Nasrallah 4 8 , Mohamed Ghaith Al-Kuwari 10 11 , Adeel A Butt 3 12 13 , Hamad Eid Al-Romaihi 14 , Mohamed H Al-Thani 14 , Abdullatif Al-Khal 3 , Hiam Chemaitelly 1 13 , Laith J Abu-Raddad 1 9 13 15
Affiliations Expand
Background: Observational studies are central to assessing vaccine effectiveness and informing public health policy. The two most common designs are test-negative case-control and cohort studies, yet direct comparisons of their performance using the same population, data sources, and analytic strategies remain rare. This study compares these two designs within a national population using harmonized analytic approaches.
Methods: Nationwide, matched test-negative case-control and retrospective cohort studies were conducted in Qatar between 1 January 2021 and 18 December 2021 to assess the effectiveness of the coronavirus disease (COVID-19) primary series of BNT162b2 and mRNA-1273 against any severe acute respiratory syndrome coronavirus 2 infection, symptomatic infection, and severe COVID-19.
Results: In the test-negative design, BNT162b2 effectiveness was 71.0% [95% confidence interval (CI): 70.1-71.9] against any infection, 75.6% (95% CI: 74.2-77.0) against symptomatic infection, and 96.3% (95% CI: 95.2-97.2) against severe COVID-19. In the cohort design, after adjustment for testing rate, corresponding effectiveness was 78.0% (95% CI: 77.1-78.9), 81.2% (95% CI: 79.8-82.5), and 98.0% (95% CI: 96.6-98.8), respectively. Both designs demonstrated similar, rapid, and largely linear waning of effectiveness in both magnitude and pattern. Test-negative design estimates lay between cohort estimates with and without adjustment for testing rate. Similar results were observed for mRNA-1273.
Conclusions: Both designs yielded consistent effectiveness estimates across vaccines and clinically relevant outcomes, with only modest differences related to handling of health-seeking behavior. These findings demonstrate that, when rigorously implemented using quality data and harmonized analytic strategies, both designs produce comparable effectiveness estimates.
Keywords: SARS-CoV-2; bias; efficacy; infection; mRNA.
. 2026 Aug 18;55(5):dyag210.
doi: 10.1093/ije/dyag210.
Evaluating COVID-19 vaccine effectiveness across epidemiologic designs: test-negative case-control versus retrospective cohort analyses in a nationwide study
Layan Sukik 1 , Pradipta Paul 1 , Houssein H Ayoub 2 , Peter Coyle 3 4 5 , Patrick Tang 6 , Mohammad R Hasan 7 , Hadi M Yassine 4 8 , Asmaa A Al Thani 4 8 , Zaina Al-Kanaani 3 , Einas Al-Kuwari 3 , Andrew Jeremijenko 3 , Anvar Hassan Kaleeckal 3 , Ali Nizar Latif 3 , Riyazuddin Mohammad Shaik 3 , Hanan F Abdul-Rahim 9 , Gheyath K Nasrallah 4 8 , Mohamed Ghaith Al-Kuwari 10 11 , Adeel A Butt 3 12 13 , Hamad Eid Al-Romaihi 14 , Mohamed H Al-Thani 14 , Abdullatif Al-Khal 3 , Hiam Chemaitelly 1 13 , Laith J Abu-Raddad 1 9 13 15
Affiliations Expand
- PMID: 42772774
- PMCID: PMC13597121
- DOI: 10.1093/ije/dyag210
Abstract
Background: Observational studies are central to assessing vaccine effectiveness and informing public health policy. The two most common designs are test-negative case-control and cohort studies, yet direct comparisons of their performance using the same population, data sources, and analytic strategies remain rare. This study compares these two designs within a national population using harmonized analytic approaches.
Methods: Nationwide, matched test-negative case-control and retrospective cohort studies were conducted in Qatar between 1 January 2021 and 18 December 2021 to assess the effectiveness of the coronavirus disease (COVID-19) primary series of BNT162b2 and mRNA-1273 against any severe acute respiratory syndrome coronavirus 2 infection, symptomatic infection, and severe COVID-19.
Results: In the test-negative design, BNT162b2 effectiveness was 71.0% [95% confidence interval (CI): 70.1-71.9] against any infection, 75.6% (95% CI: 74.2-77.0) against symptomatic infection, and 96.3% (95% CI: 95.2-97.2) against severe COVID-19. In the cohort design, after adjustment for testing rate, corresponding effectiveness was 78.0% (95% CI: 77.1-78.9), 81.2% (95% CI: 79.8-82.5), and 98.0% (95% CI: 96.6-98.8), respectively. Both designs demonstrated similar, rapid, and largely linear waning of effectiveness in both magnitude and pattern. Test-negative design estimates lay between cohort estimates with and without adjustment for testing rate. Similar results were observed for mRNA-1273.
Conclusions: Both designs yielded consistent effectiveness estimates across vaccines and clinically relevant outcomes, with only modest differences related to handling of health-seeking behavior. These findings demonstrate that, when rigorously implemented using quality data and harmonized analytic strategies, both designs produce comparable effectiveness estimates.
Keywords: SARS-CoV-2; bias; efficacy; infection; mRNA.