Which patient subgroups (severity, comorbidity, PDE5i responders) show the greatest randomized‑trial benefit from LiSWT?
Executive summary
There are no LiSWT–specific randomized‑trial subgroup results in the provided reporting, so any statement about which patients definitively derive the greatest randomized‑trial benefit from low‑intensity shockwave therapy must be qualified as hypothesis rather than established fact (limitation of available sources) [1]. What can be stated confidently from trial methodology literature is how to identify and interpret subgroup effects—namely that pre-specification, adequate power, and interaction testing are essential, and that apparent subgroup “benefits” from post hoc slicing of trial data are frequently false leads [1] [2] [3].
1. How the question should be framed: what “benefit” and which scale matters
Whether a subgroup shows the “greatest benefit” depends on metric: relative effects (risk ratios) can look uniform across subgroups while absolute effects differ sharply when baseline risk or severity varies, so targeting patients with higher baseline risk can produce larger absolute gains even if relative efficacy is constant [4]. Any statement about LiSWT subgroup benefit therefore needs clarity on whether the endpoint of interest is absolute symptom improvement, responder rate, quality‑of‑life gain, or a relative risk metric [4].
2. The methodological guardrails: pre‑specification, power and multiplicity
Credible subgroup claims require pre‑specified hypotheses and sufficient power to test interaction terms; post hoc analyses inflate type I error and should be treated as hypothesis‑generating rather than confirmatory [1] [2] [3]. Trials that do attempt subgroups must control for multiple comparisons or limit the number of subgroup factors, otherwise chance findings dominate [5] [2].
3. Severity‑defined subgroups: why more severe disease might show larger absolute gains
Designing trials to compare patients by baseline severity is sensible because higher baseline event rates or worse function produce larger absolute differences for the same relative effect; therefore, randomized evidence that LiSWT benefits “severe” cases would be most persuasive if severity strata were pre‑specified and interaction tested, but the reporting does not provide LiSWT trial data to confirm this pattern [6] [4]. Importantly, selecting only high‑risk or severe patients can improve the net benefit for a trial, but must be justified a priori [6].
4. Comorbidity as moderator: plausible, but confounded unless planned
Comorbid conditions can modify treatment effects or simply alter baseline prognosis; subgroup estimates for comorbidity strata are valid only if planned and analyzed as interactions because confounding between comorbidity, age, and other factors can distort apparent differences [4] [7]. The literature advises that controlling for confounding is unnecessary only when the subgroup factor itself is the target of an intervention—otherwise, careful modeling and pre‑specification are required [4].
5. PDE5i responder status: a high‑value, hypothesis‑driven subgroup to test
Whether prior response to PDE5 inhibitors predicts LiSWT benefit is a biologically and clinically plausible moderator worthy of pre‑specified testing, but absent randomized evidence in the provided sources, it remains a hypothesis; trials should treat PDE5i responder status as a stratification factor or a planned interaction to preserve power and interpretability [3] [8]. If PDE5i response is used to stratify allocation, small trials must limit the number of strata to avoid loss of efficiency [8].
6. Practical roadmap for credible LiSWT subgroup claims
To credibly show which patients—by severity, comorbidity, or PDE5i response—benefit most, investigators should predefine a small number of clinically plausible subgroups, power the trial or meta‑analysis for interaction testing where possible, report point estimates with confidence intervals rather than over‑relying on post hoc p‑values, and, where data‑driven methods are used, treat the findings as hypothesis‑generating for a subsequent confirmatory randomized trial [1] [5] [7] [3]. Without LiSWT‑specific randomized subgroup data in the cited material, recommendations about particular subgroups must remain provisional and framed as the appropriate next steps for trialists [1] [2].