Absolute risk reduction for shingrix vaccine
Executive summary
vaccine-safety">Shingrix’s headline relative efficacy (>90% reduction in shingles cases in trials) masks a much smaller absolute risk reduction (ARR): roughly 3.3–3.6 percentage points over about 3–4 years for immunocompetent adults, which translates to a number needed to vaccinate (NNV) in the high 20s to low 30s to prevent one case of herpes zoster and an NNV of roughly 350 to prevent one case of post‑herpetic neuralgia (PHN) [1] [2] [3].
1. What “absolute risk reduction” means for Shingrix in plain numbers
Absolute risk reduction compares the actual difference in event rates between vaccinated and unvaccinated groups; in the pivotal trials and systematic reviews that difference for confirmed herpes zoster was about 3.3–3.54% over roughly 3.5–4 years (Therapeutics Letter reports 3.26% over 3.5 years and a Cochrane-style summary and BMJ correspondence report 3.54%), giving an NNV ≈ 28–31 to prevent one case of shingles, while the ARR for PHN is about 0.28–0.3% (NNV ≈ 350) [3] [2] [4].
2. How trial relative efficacy and absolute reduction can both be true
Trials show very large relative risk reductions — for example, Shingrix reduced incidence vs placebo by ~97% in the ZOE trial data cited in the FDA and manufacturer materials — but those large relative gains come from lowering a relatively low baseline risk, so the absolute difference in the population over the trial period is only a few percentage points [1] [5] [6].
3. Real-world performance and population context change the arithmetic
Post‑licensure and observational studies show lower effectiveness than trials in some settings: large real‑world cohorts report effectiveness in the 50–80% range depending on outcome and population, and incidence rates used to compute ARR vary by age and baseline risk; for example, trial incidence was ~9.1 per 1,000 person‑years in placebo versus 0.3 per 1,000 in vaccine recipients (a reduction of about 8.8 cases per 1,000 person‑years in trial cohorts), while population studies translate to differences like “5 fewer cases per 10,000 person‑years” for rarer outcomes such as ophthalmic zoster in some HTA reports [7] [8] [9] [10].
4. Harms, tradeoffs and the NNV/NNH calculus
The same reviews that calculated ARR note increased short‑term systemic reactogenicity: grade‑3 systemic reactions that interfere with daily activities were increased by about 4–9% with Shingrix in trials, producing a number needed to harm (NNH) in the low double digits (≈11–25 for disabling short‑term reactions), so decision‑making depends on weighing preventing one case of HZ (NNV ≈ 28–31) and one PHN (NNV ≈ 350) against the chance of significant but transient vaccine reactions [3].
5. Who gains most from the absolute reduction — and where uncertainty remains
Absolute benefit grows with baseline risk: immunocompromised or older people have higher incidence of shingles, so the same relative efficacy prevents more cases per 1,000 vaccinations (HTA reporting showed many more cases avoided per 10,000 person‑years in high‑risk groups) while durability beyond four years and long‑term safety signals (rare events such as GBS observed in postmarketing surveillance) remain areas with incomplete evidence in some groups [9] [3] [11].
6. Takeaway for policy and individual-level choices
Policymakers and clinicians should present both relative efficacy and the absolute risk numbers: Shingrix dramatically lowers the risk of shingles on a relative scale, but the absolute reduction over several years is a few percentage points in average‑risk older adults (NNV ≈ 28–31 for HZ, ≈350 for PHN), balanced against a meaningful short‑term reactogenicity signal and continuing questions about long‑term durability and very rare adverse events — tradeoffs that change if baseline risk is higher or if population priorities focus on reducing severe complications [2] [3] [1].