Use of patient-reported outcomes in randomized, double-blind, placebo-controlled clinical trials.

BACKGROUND: To optimize the use of patient-reported outcomes (PROs) in clinical research, it is first necessary to review the current use of these outcomes in clinical trials to determine under what circumstances they are most useful, and to reveal current limitations. PURPOSE: To investigate current patterns of use of PROs in clinical trials. RESEARCH DESIGN: We conducted a systematic literature review of all double-blind, placebo-controlled, randomized clinical trials using one or more PROs as a study outcome from 2004 to 2006. Data were abstracted and analyzed with descriptive statistics and logistic regression to characterize the use of PROs in clinical trials. RESULTS: The 180 clinical trials that met the study inclusion criteria used 173 unique instruments to measure a total of 466 PROs. Most PRO measurements were obtained using relatively few PRO instruments, with one-third of PRO instruments applied in more than 1 trial. In multivariable analysis, tests of statistical significance were more often reported for PROs used as primary trial outcomes. Statistically significant PRO outcomes (P<0.05) were more likely among disease-specific PROs compared with general PROs, PROs with a discussion of minimally important difference, and larger trials. CONCLUSIONS: PRO instruments may be improved through efforts to provide centralized electronic administration, cross-validation, and standardized interpretation of clinically relevant outcomes. The majority of PROs used in current clinical trials come from relatively few, commonly used disease-specific PRO instruments within major therapeutic areas.

Expectations of benefit in early-phase clinical trials: implications for assessing the adequacy of informed consent.

BACKGROUND: Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented, which is based on assumptions about what patients mean when responding to questions about likelihood of benefit. METHODS: Participants were 27 women and 18 men in early-phase oncology trials at 2 academic medical centers in the United States. To determine whether expectations of benefit differ depending on how patients are queried, the authors randomly assigned participants to 1 of 3 interviews corresponding to 3 questions about likelihood of benefit: frequency type, belief type, and vague. In semistructured interviews, participants were queried about how they understood and answered the question. Participants then answered and discussed 1 of the other questions. RESULTS: Expectations of benefit in response to the belief-type question were significantly greater than expectations in response to the frequency-type and vague questions (P=0:02). The most common justifications involved positive attitude (n=27 [60%]) and references to physical health (n=23 [51%]). References to positive attitude were most common among participants with higher (> 70%) expectations (n = 11 [85%]) and least common among those with lower ( < 50%) expectations (n = 3 [27%]). CONCLUSIONS: The wording of questions about likelihood of benefit shapes the expectations that patients express. Patients who express high expectations may not do so to communicate understanding but rather to register optimism. Ongoing research will clarify the meaning of high expectations and examine methods for assessing understanding.

Publication or presentation of results from multicenter clinical trials: evidence from an academic medical center.

BACKGROUND: Nonpublication of research results threatens the integrity of clinical research, but the extent of nonpublication and factors associated with publication remain poorly documented. We sought to examine rates of publication or presentation of research findings from multicenter clinical trials and determine what factors are associated with dissemination of results. METHODS: We conducted a follow-up study of 217 prospective, multicenter clinical trials of treatment approved in 1998 by the institutional review board of a large academic medical center, of which 197 had enrolled participants and were not known to be ongoing. Follow-up included searches of the literature and the Internet and telephone and e-mail inquiries to investigators and research sponsors. The main outcome measures were manuscript publication or other presentation of research results. RESULTS: Results of 110 (56%) out of 197 multicenter clinical trials have been published in the peer-reviewed literature. Results of 87 (44%) studies have not been published, and results of 52 (26%) studies have not been disseminated in any form. The rate of dissemination of trial results was highest for studies that were phase 3 (81%), lowest risk (86%), and investigational (76%). The dissemination rate was lowest for studies that were supported by internal funds (50%). However, none of these associations were statistically significant. CONCLUSIONS: Results of almost half of the multicenter clinical trials conducted in part at a large academic medical center have never been published. Mechanisms to ensure public dissemination of clinical trial results are needed.