Rationale and objectives: We assessed how well published randomized controlled trials (RCTs) of peripheral thrombolysis have been designed and how they adjusted for patient characteristics that may influence responses to therapy.
Methods: RCT studies published between 1984 and 1994 were reviewed to determine whether they included nine crucial elements: sample size calculations, description of unenrolled eligible participants, homogeneous samples, balanced experimental groups, equal potency therapies, equal follow-up of outcomes, appropriate statistical inference, multivariable or subgroup analyses, and anonymous review of subjective endpoints.
Results: The nine RCTs complied with a median of three of nine standards (range = 2-6). Each report exhibited serious flaws that may affect generalizability and external validity. None adequately adjusted for sample heterogeneity or sought to identify characteristics that may affect responses to therapy.
Conclusion: Failure to address prognostic or confounding variables restricts the utility of peripheral thrombolysis RCTs and helps explain why contentious debates about this therapy persist. A model for future thrombolysis trials is proposed.