The abstract:
Results Of 49 highly cited original clinical research studies, 45 claimed that the intervention was effective. Of these, 7 (16%) were contradicted by subsequent studies, 7 others (16%) had found effects that were stronger than those of subsequent studies, 20 (44%) were replicated, and 11 (24%) remained largely unchallenged. Five of 6 highly-cited nonrandomized studies had been contradicted or had found stronger effects vs 9 of 39 randomized controlled trials (P = .008). Among randomized trials, studies with contradicted or stronger effects were smaller (P = .009) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact. Matched control studies did not have a significantly different share of refuted results than highly cited studies, but they included more studies with “negative” results.
Conclusions Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes. The extent to which high citations may provoke contradictions and vice versa needs more study. Controversies are most common with highly cited nonrandomized studies, but even the most highly cited randomized trials may be challenged and refuted over time, especially small ones.