Suchergebnisse

Certain limitations of evidence available on drugs and devices at the time of market approval often persist in the post-marketing period. Often, post-marketing research landscape is fragmented. When regulatory agencies require pharmaceutical and device manufacturers to conduct studies in the post-marketing period, these studies might remain incomplete many years after approval. Even when completed, many post-marketing studies lack meaningful active comparators, have observational designs, and might not collect patient-relevant outcomes. Regulators, in collaboration with the industry and patients, ought to ensure that the key questions unanswered at the time of drug and device approval are resolved in a timely fashion during the post-marketing phase. We propose a set of seven key guiding principles that we believe will provide the necessary incentives for pharmaceutical and device manufacturers to generate comparative data in the post-marketing period. First, regulators (for drugs and devices), notified bodies (for devices in Europe), health technology assessment organisations, and payers should develop customised evidence generation plans, ensuring that future post-approval studies address any limitations of the data available at the time of market entry impacting the benefit–risk profiles of drugs and devices. Second, post-marketing studies should be designed hierarchically: priority should be given to efforts aimed at evaluating a product's net clinical benefit in randomised trials compared with current known effective therapy, whenever possible, to address common decisional dilemmas. Third, post-marketing studies should incorporate active comparators as appropriate. Fourth, use of non-randomised studies for the evaluation of clinical benefit in the post-marketing period should be limited to instances when the magnitude of effect is deemed to be large or when it is possible to reasonably infer the comparative benefits or risks in settings, in which doing a randomised trial is not feasible. Fifth, efficiency of randomised trials should be improved by streamlining patient recruitment and data collection through innovative design elements. Sixth, governments should directly support and facilitate the production of comparative post-marketing data by investing in the development of collaborative research networks and data systems that reduce the complexity, cost, and waste of rigorous post-marketing research efforts. Last, financial incentives and penalties should be developed or more actively reinforced.

Objectives: Depression symptom questionnaires are not for diagnostic classification. Patient Health Questionnaire-9 (PHQ-9) scores >= 10 are nonetheless often used to estimate depression prevalence. We compared PHQ-9 >= 10 prevalence to Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) major depression prevalence and assessed whether an alternative PHQ-9 cutoff could more accurately estimate prevalence. Study Design and Setting: Individual participant data meta-analysis of datasets comparing PHQ-9 scores to SCID major depression status. Results: A total of 9,242 participants (1,389 SCID major depression cases) from 44 primary studies were included. Pooled PHQ-9 >= 10 prevalence was 24.6% (95% confidence interval [CI]: 20.8%, 28.9%); pooled SCID major depression prevalence was 12.1% (95% CI: 9.6%, 15.2%); and pooled difference was 11.9% (95% CI: 9.3%, 14.6%). The mean study-level PHQ-9 >= 10 to SCID-based prevalence ratio was 2.5 times. PHQ-9 >= 14 and the PHQ-9 diagnostic algorithm provided prevalence closest to SCID major depression prevalence, but study-level prevalence differed from SCID-based prevalence by an average absolute difference of 4.8% for PHQ-9 >= 14 (95% prediction interval: -13.6%, 14.5%) and 5.6% for the PHQ-9 diagnostic algorithm (95% prediction interval: -16.4%, 15.0%). Conclusion: PHQ-9 >= 10 substantially overestimates depression prevalence. There is too much heterogeneity to correct statistically in individual studies. ; Canadian Institutes of Health Research (CIHR) KRS-134297 PCG155468 PJT-162206 Fonds de recherche du Quebec -Sante (FRQS) Postdoctoral Training Fellowships FRQS Research Institute of the McGill University Health Centre G.R. Caverhill Fellowship from the Faculty of Medicine, McGill University Vanier Canada Graduate Scholarship Canadian Institutes of Health Research (CIHR) Cumming School of Medicine, University of Calgary Alberta Health Services through the Calgary Health Trust Hotchkiss Brain Institute Alberta Innovates Health Solutions Canada Research Chair in Neurological Health Services Research AIHS Population Health Investigator Award Department of Education (NIDRR) H133B080025 National Multiple Sclerosis Society MB 0008 Lundbeck International Tehran University of Medical Sciences M-288 Canadian Institutes of Health Research (CIHR) THC-135234 Crohn's and Colitis Canada Bingham Chair in Gastroenterology Waugh Family Chair in Multiple Sclerosis UK Department for International Development 201446 Department of Education, National Institute on Disability and Rehabilitation Research, Spinal Cord Injury Model Systems: University of Washington H133N060033 Baylor College of Medicine H133N060003 University of Michigan System H133N060032 Grand Challenges Canada 0087-04 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Mental Health (NIMH) R24MH071604 R34 MH072925 K02 MH65919 P30 DK50456 R24 MH56858 RO1-MH069666 R24 MH071604 MH014592-38 MH103210 United States Department of Health & Human Services Centers for Disease Control & Prevention - USA R49 CE002093 Spanish Ministry of Health's Health Research Fund (Fondo de Investigaciones Sanitarias) 97/1184 US National Center for Medical Rehabilitation Research RO1 HD39415 Federal Ministry of Education & Research (BMBF) 01GY1150 University of Technology Sydney Duke Global Health Institute 453-0751 Macao (SAR) Government, through the University of Macau RSKTO grants MYRG-2014-111 United States Agency for International Development (USAID) AID-DFD A-00-08-00308 UK National Institute for Health Research under its Programme Grants for Applied Research Programme RP-PG0606-1142 Consejo Nacional de Ciencia y Tecnologia (CONACyT) CB-2009133923-H National Health Research Institutes - Taiwan NHRI-EX97-9706PI Reitoria de Pesquisa da Universidade de Sao Paulo 09.1.01689.17.7 Banco Santander 10.1.01232.17.9 Pfizer medical faculty of the University of Heidelberg, Germany 121/2000 Research Manitoba Chair in Multiple Sclerosis Canadian Institutes of Health Research (CIHR) Niigata Seiryo University Productivity Grants (PQ-CNPq-2) 301321/2016-7 Ministry of Health, Italy United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) U10CA21661 U10CA180868 U10CA180822 U10CA37422 Pennsylvania Department of Health United Kingdom National Health Service Lothian Neuro-Oncology Endowment Fund United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) K07 CA 093512 Lance Armstrong Foundation United States Department of Health & Human Services United States Health Resources & Service Administration (HRSA) R40MC07840 United States Department of Health & Human Services National Institutes of Health (NIH) - USA T32 GM07356 United States Department of Health & Human Services Agency for Healthcare Research & Quality R36 HS018246 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Research Resources (NCRR) TL1 RR024135 medical faculty, University of Leipzig Hunter Medical Research Institute Netherlands Organization for Health Research and Development (ZonMw) Mental Health Program 100.003.005 100.002.021 Academic Medical Center/University of Amsterdam Fund for Innovation and Competitiveness of the Chilean Ministry of Economy, Development and Tourism, through the Millennium Scientific Initiative IS130005 Research Manitoba Chair