Kwok-Chiu Chang and Fuk-Yip Kong suggest that possible selection bias in our nested case-control study could be due to the control participants (ie, patients admitted to emergency rooms or hospital wards) being older than all participants eligible for vaccination in the general population. However, as we used a matched case-control study design, this concern is irrelevant. As stated in our methods, we matched each case with a control using the exact year of age in our analysis. Hence, the hypothetical example for potential selection bias referred to by Chang and Kong does not apply to our study.
We acknowledge that the health of participants eligible for vaccination might be relatively better than the health of our control participants. A possible reason is that relatively healthy individuals with high-risk occupations were given priority for vaccination in the rollout schedule of the vaccination programme in Hong Kong, which is included in our study.2 We addressed this issue in our analysis by adjusting baseline characteristics, including comorbidities and concurrent medication use. Therefore, such characteristics should not have had a significant effect on our results or conclusions.
To further address Chang and Kong's concern on the difference in baseline characteristics between cases and controls,1 we conducted further post-hoc sensitivity analysis by excluding control participants with neoplasms or exposure to antibacterial drugs because there were substantial differences between cases and controls (neoplasm 5% vs 13%; antibacterial drugs 7% vs 13%).1 The results were similar to the main findings (table ), which further supports the robustness of our study.
Table.
Sensitivity analysis excluding control participants with neoplasms or antibacterial drugs used in the nested case-control study
| Number of patients (n=295)* | Number of control participants (n=908) | Crude odds ratio (95% CI) | p value | Adjusted odds ratio (95% CI) | p value | |
|---|---|---|---|---|---|---|
| Not vaccinated | 253 (86%) | 828 (91%) | ref | .. | ref | .. |
| CoronaVac | 28 (9%) | 50 (6%) | 2·049 (1·221–3·438) | 0·0066 | 2·196 (1·293–3·728) | 0·0036 |
| BNT162b2 | 14 (5%) | 30 (3%) | 1·636 (0·842–3·178) | 0·15 | 1·745 (0·888–3·430) | 0·11 |
Cases and controls were matched according to age, sex, setting, and admission date. Odds ratios for Bell's palsy were estimated by conditional logistic regression adjusted for smoking status, pre-existing comorbidities (ie, diabetes, hypertension, asthma, rheumatoid arthritis, stroke, and migraine), infections in the past 90 days (acute respiratory infections), and medication use in the past 90 days (antiviral drugs, systemic corticosteroids, immunosuppressants).
Three patients were excluded as the corresponding control participants were excluded because of neoplasms or the antibacterial drugs used.
As is the case for all observational studies, the effect of unmeasured confounding in our nested case-control study cannot be completely ruled out. The self-controlled case series method has become a popular alternative study design for drug safety studies.2 It was specifically developed to evaluate vaccine safety with the advantage of reducing unmeasured confounding through the comparisons within individuals.3, 4 Because of the small number of events and a short follow-up period in our study, we were unable to apply such a method. We appreciate Chang and Kong's interest in our study and, as stated in our paper, further study is warranted to confirm our findings.
ICKW reports research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GlaxoSmithKline, Novartis, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia. ICKW also reports receiving speakers fees from Janssen and Medice, outside the submitted work. ICKW is also an independent non-executive director of Jacobson Medical in Hong Kong. EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region (SAR), and the Hong Kong Research Grants Council, outside the submitted work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen, and personal fees from Primevigilance, outside the submitted work. XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer, internal funding from the University of Hong Kong, and consultancy fees from Merck Sharp & Dohme, outside the submitted work. EWYC reports honorarium from Hospital Authority, grants from the Hong Kong Research Grants Council, Research Fund Secretariat of the Food and Health Bureau, grants from National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and the Narcotics Division of the Security Bureau of the Hong Kong SAR, outside the submitted work.
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