The FDA continues to approve PRO claims, with 24% of new molecular entities and biologic license applications being granted. Successful PRO label claims over the past 5 years have generally supported treatment benefit for symptoms specified as primary endpoints.

There are quite a few disorders for which regulatory agencies have required a treatment to demonstrate a statistically significant effect on multiple endpoints, each at the one-sided 2.5% level, before accepting the treatment's efficacy for the disorders. Depending on the correlation among the endpoints, this requirement could lead to a substantial reduction in the study's power to conclude the efficacy of a treatment. To investigate the prevalence of this requirement and propose possible solutions, a multiple-disciplinary Multiple Endpoints Expert Team sponsored by Pharmaceutical Research and Manufacturers of America was formed in November 2003. The team recognized early that many researchers were not fully aware of the implications of requiring multiple co-primary endpoints. The team proposes possible solutions from both the medical and the statistical perspectives. The optimal solution is to reduce the number of multiple co-primary endpoints. If after careful considerations, multiple co-primary endpoints remain a scientific requirement, the team proposes statistical solutions and encourages that regulatory agencies be receptive to approaches that adopt modest upward adjustments of the nominal significance levels for testing individual endpoints. Finally, the team hopes that this report will draw more attention to the problem of multiple co-primary endpoints and stimulate further research.

ObjectiveThis review was undertaken to assess the historical evidence of the disease incidence and burden of laboratory-confirmed respiratory syncytial virus (RSV) in medically attended older adults.DesignA qualitative systematic literature review was performed; no statistical synthesis of the data was planned, in anticipation of expected heterogeneity across studies in this population.MethodsA literature search of PubMed, Embase, and the Cochrane Library was conducted for studies of medically attended RSV in older adults (≥ 50 years) published in the last 15 years. Two independent reviewers screened titles and abstracts based on predefined inclusion and exclusion criteria.ResultsFrom 10 studies reporting incidence proportions, RSV may be the causative agent in up to 12% of medically attended acute respiratory illness in older adults unselected for comorbidities, with variations in clinical setting and by year. In multiple studies, medically attended–RSV incidence among older adults not selected for having underlying health conditions increased with increasing age. Of prospectively followed lung transplant recipients, 16% tested positive for RSV. In hospitalized adults with chronic cardiopulmonary diseases, 8% to 13% were infected with RSV during winter seasons (8%-13%) or metapneumovirus season (8%). Hospitalizations for RSV in older adults typically lasted 3 to 6 days, with substantial proportions requiring intensive care unit admission and mechanical ventilation. Among older adults hospitalized with RSV, the mortality rate was 6% to 8%.ConclusionsProtection of older adults against RSV could reduce respiratory-related burden, especially as age increases and the prevalence of comorbidities (especially cardiopulmonary comorbidities) grows.

The CTSQ was designed for adults with a wide range of cancer types and stages, receiving a variety of cancer treatment formulations. A validation study is currently underway to examine the psychometric properties, further refine the questionnaire and develop scoring methods for the CTSQ.

These results provide more precise information regarding patient treatment concerns than that provided by the usual measurement of HRQOL. This information can be used by clinical trial investigators to design more precise interventions to improve HRQOL in the domains of greatest importance to patients and by all health care professionals to improve counseling of patients.