Cost-Effectiveness of Herpes Zoster Vaccine: Flawed Assumptions Regarding Efficacy against Postherpetic Neuralgia
Bibliographic record
Abstract
To the Editor—Rothberg et al. [1] examined the cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia (PHN). The authors concluded that the cost-effectiveness of the herpes zoster vaccine varies substantially with patient age and often exceeds US$100,000 per quality-adjusted life-year saved. Although these conclusions are dependant on a number of parameter choices that are based on limited or uncertain data (e.g., PHN-related costs, PHN incidence, and duration of vaccine efficacy [2]), one major assumption is erroneous—namely that there is no reduction in the incidence of PHN beyond that afforded by reducing the incidence of herpes zoster. The authors based this assumption on a non-age-adjusted aggregate analysis of the 4-year follow-up data from the Shingles Prevention Study [3] and on the following rationale: (1) vaccination appeared to prevent PHN during the first year following vaccination, but it had no statistically significant additional efficacy during subsequent years, and (2) the apparent efficacy during the first year was because of a significantly higher rate of PHN among placebo recipients during the year following vaccination, relative to subsequent years, rather than because of any reduction in the incidence of PHN among vaccinated subjects (results are presented in table 2 in the article by Rothberg et al. [1]). Because, in the Shingles Prevention Study [3], herpes zoster vaccine efficacy against herpes zoster decreased with age (from 64% among subjects aged 60–69 years to 38% among subjects aged ⩾70 years) and vaccine efficacy against PHN remained constant with age (66% among subjects aged 60–69 years and 67% among subjects aged ⩾70 years), additional vaccine efficacy against PHN would be expected to be age dependant. Therefore, an age-stratified analysis is necessary to accurately examine whether the herpes zoster vaccine reduces the incidence of PHN beyond the reduction in PHN incidence provided by preventing herpes zoster. We present the age-specific conditional efficacy of the herpes zoster vaccine in preventing PHN in the Shingles Prevention Study (table 1). Results clearly reveal that, although there was no significant additional efficacy in preventing PHN in subjects aged 60–69 years, the vaccine efficacy in preventing PHN among subjects with herpes zoster who were aged ⩾70 years was 49% (P = .01) (table 1). The vaccine efficacy in preventing PHN among subjects with herpes zoster who were aged ⩾70 years remained statistically significant, even after making a modification—similar to that of Rothberg et al. [1]—to the empirical PHN rate in the placebo arm in the first year of the Shingles Prevention Study (table 1). Age-specific efficacy of vaccine in preventing postherpetic neuralgia (PHN) over 4 years of follow-up in the Shingles Prevention Study [3]. Assuming that there is no reduction in the incidence of PHN beyond that afforded by reducing the incidence of herpes zoster can have a substantial impact on predictions of the cost-effectiveness of herpes zoster vaccination. Using our cohort model of herpes zoster vaccine cost-effectiveness [2] and using assumptions regarding duration of vaccine efficacy (10 years) and PHN-related costs (US$566) that were similar to those of Rothberg et al. [1], we estimated that including the additional zoster vaccine efficacy against PHN reduces the cost per quality-adjusted life-year among adults aged 70 and 80 years by ∼10% and ∼40%, respectively. Including the additional vaccine efficacy against PHN will increase the sensitivity of cost-effectiveness results to assumptions about duration of efficacy and other PHN-related parameters. Rothberg et al. [1] are underestimating the cost-effectiveness of herpes zoster vaccination for adults aged >70 years. Potential conflicts of interest. M.B. has received consultation fees from Merck and reimbursement for travel expenses from GlaxoSmithKline. J.M.P. is an employee of Merck. M.J.L. has received consultation fees and lecture fees from Merck and shares a patent for the idea of a zoster vaccine with Merck.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.018 | 0.150 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.023 | 0.015 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".