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Excerpt
In (a), meaningful clinical studies can be designed to test whether the proposed BMP treatment is equivalent or superior to the standard of care. For example, recombinant human (rh) BMP-2 is being tested as a complete replacement for the use of autograft in several spine fusion procedures. These clinical studies compare the outcomes of patients who have been randomized to receive rhBMP-2 or autograft. All patients receive the same spine instrumentation. The control group (autograft) was chosen because it represents the current standard of care. The most conservative design for studies of this sort is one that will definitively establish the statistical equivalence of the two treatments. The size of each group should be sufficiently large to allow a conclusion that the outcome of the two treatments differs by no more than a small amount (e.g., ±10%) and should limit the probability of a type II error (not detecting a difference that actually exists) to less than 20%.
In (b), the only meaningful design for a clinical study is one that tests whether the proposed BMP treatment is superior to the standard of care. For example, rhBMP-2 is being tested as an adjunct to standard surgical care in the acute treatment of open tibial fractures that require surgical management. In a study of this sort, every patient receives the standard of care (in this case, internal fixation with an intramedullary nail), and patients are randomized to receive either no additional treatment or rhBMP-2 treatment. The control group does not offer an alternative to BMP, because there is no alternative adjuvant treatment currently available.
The most conservative study design for studies of this sort is one that will detect relatively small differences between the control group and the BMP treatment group. However, statistically significant differences are not sufficient for these studies to be meaningful. The differences detected in these types of studies must also be clinically meaningful and represent a true clinical benefit for the patient.
In summary, the intended use of BMP treatment (and its relationship to the existing surgical standard of care) directly affects the design of clinical studies that evaluate that particular intended use. Most importantly, this relationship determines the choice of the appropriate control group, an essential requirement for any clinical study to yield definitive safety and efficacy results.
