Predictors for independent external validation of cardiovascular risk clinical prediction rules: Cox proportional hazards regression analyses

Background: Clinical prediction rules (CPRs) should be externally validated by independent researchers. Although there are many cardiovascular CPRs, most have not been externally validated. It is not known why some CPRs are externally validated by independent researchers and others are not. Methods: We analyzed cardiovascular risk CPRs included in a systematic review. Independent external validations were identified by forward citation searches of derivation studies. Time between the publication of a cardiovascular CPR and the first independent external validation was calculated. We assessed Kaplan-Meier estimates of the probability to have an independent external validation. Using univariable Cox regression, we explored whether characteristics of derivation (design, location, sample size, number of predictors, presentation format, validation in derivation), reporting (participants, predictors, outcomes, performance measure, information for risk calculation), and publication (journal impact factor) are associated with time to the first independent external validation. Results: Of 125 cardiovascular risk CPRs, 29 had an independent external validation. The median follow-up was 118 months (95% CI, 99–130). The 25th percentile of event time was 122 months (95% CI, 91–299). Cardiovascular risk CPRs from the USA were 4.15 times (95% CI, 1.89–9.13) more likely to have an independent external validation. Increasing the sample size of derivation by ten times was associated with a 2.32-fold (95% CI, 1.37–3.91) increase in the probability of having an independent external validation. CPRs presented with an internal validation tend to get an independent external validation sooner (HR = 1.73, 95% CI, 0.77–3.93). CPRs reporting all the information necessary for calculating individual risk were 2.65 (95% CI, 1.01–6.96) times more likely to have an independent external validation. Publishing a cardiovascular risk CPR in a journal that has one unit higher impact factor was associated with a 6% (95% CI, 3–9) higher likelihood of an independent external validation. Conclusions: The probability for cardiovascular risk CPRs to get an independent external validation was low even many years after their derivations. Authors of new cardiovascular risk CPRs should consider using adequate sample size, conducting an internal validation, and reporting all the information needed for risk calculation as these features were associated with an independent external validation.