Table 5 The barriers and facilitators mapped to the balancing internal vs external validity theme

Certain disabilities may put participants at higher risk of complications and side effects, or make them less likely to have a meaningful response to experimental therapy which can impact efficacy and safety conclusions [17, 41]

Reporting key baseline characteristics for the study cohort and recruiting large sample sizes allows stratification of results and allows statistical adjustments to be carried out to account for covariates [10]

Medication washout isn’t feasible for many disabled people introducing risk of adverse drug interactions [21, 27]

Eligibility criteria can incorporate scores from sensitive assessment tools that relate to the confounding factor itself rather than proxies (e.g. using a Frailty Index instead of age) [10]

Certain confounders are prevalent among disabled populations and so exclusion from study populations greatly reduces generalisability [42]. For example, exclusion of people with psychiatric disorders from smoker populations [30]

Using standardised tools rather than clinical judgement may reduce the exclusion of individuals based on discriminatory biases that may be held by investigators [33]

Unjustified ambiguous exclusion criteria that leave exclusion largely to researchers discretion enables discriminatory sampling [42]