General cardiologyAbstractContradicted and Initially Stronger Effects in Highly Cited Clinical Research
Section snippets
Study Question
To understand how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time.
Methods
The researcher examined all original clinical research studies published in three major general clinical journals or high-impact-factor specialty journals between 1990–2003 and cited more than 1000 times in the literature. The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled designs. The same analysis was also performed comparatively for matched studies that were not so highly cited.
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 versus 9 of 39 randomized controlled trials (p=0.008). Among randomized trials,
Conclusions
The conclusion was that contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes.
Perspective
This innovative study suggests that contradiction and initially stronger effects are common in highly cited research. The extent to which high cited studies 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 studies with modest sample size. Clinical research is time-consuming, and challenging results may take several