THE EFFECT OF THERAPEUTIC TREATMENT CROSSOVERS ON THE POWER OF CLINICAL-TRIALS

The Silicone Study is a randomized clinical trial comparing two surgical methods for reattaching the retina when detachment is associated with proliferative vitreoretinopathy. If the retina redetaches subsequently, the patient will usually undergo additional surgery using the assigned treatment. In a limited number of cases the patient may be switched to the alternative treatment, if a "therapeutic crossover" is endorsed by an independent committe of ophthalmologists. A successful outcome is continued anatomic attachment of the retina and an adequate visual result 6 months after the final surgery. The therapeutic treatment crossover affect the power of the trial to detect a difference between the two treatments. A simulation study shows that the loss in power depends on the magnitude and degree of bias in the probability of being switched from one treatment to the other. Unlike the usual case of lack of compliance, complete information about treatment history may allow statistical adjustment for the crossover. The outcome may be modeled using a multinomial distribution. Much of the power lost due to switching may be recouped under some strong assumptions. © 1990.