title: Designing "Real-World" trials to meet the needs of health policy makers at marketing authorization.
abstract: OBJECTIVE
  There is increasing interest in conducting "Real-World" trials that go beyond traditional assessment of efficacy and safety to examine market access and value for money questions before marketing authorization of a new pharmaceutical product or health technology. This commentary uses practical examples to demonstrate how high-quality evidence of the cost-effectiveness of an intervention may be gained earlier in the development process.
  
  
  METHODS
  Issues surrounding the design and analysis of "Real-World" trials to demonstrate relative cost-effectiveness early in the life of new technologies are discussed. The modification of traditional phase III trial designs, de novo trial designs, the combination of trial-based and epidemiological data, and the use of simulation model-based approaches to address reimbursement questions are described.
  
  
  RESULTS
  Modest changes to a phase III trial protocol and case report form may be undertaken at the design stage to provide valid estimates of health care use and the benefits accrued; however, phase III designs often preclude "real-life" practice. Relatively small de novo trials may be used to address adherence to therapy or patient preference, although simply designed studies with active comparators enrolling large numbers of patients may provide evidence on long-term safety and rare adverse events.
  
  
  CONCLUSIONS
  Practical examples demonstrate that it is possible to provide high-quality evidence of the cost-effectiveness of an intervention earlier in the development process. Payers and decision makers should preferentially adopt treatments with such evidence than treatments for which evidence is lacking or of lower quality.
authors: Health Care Evaluation Group, School of Health and Population Sciences, Primary Care and Clinical Sciences Building, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. M.Calvert@bham.ac.uk
authors: Melanie
authors: M
authors: Calvert
authors: John
authors: J
authors: Wood
authors: Nick
authors: N
authors: Freemantle
mesh_terms: D019985:Benchmarking / Q000191:economics; D020811:Biomedical Technology; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003362:Cost-Benefit Analysis; D004345:Drug Industry / Q000191:economics / Q000592:standards; D006801:Humans; D040541:Marketing / Q000191:economics / Q000592:standards*; D010349:Patient Compliance; D011786:Quality Control; D012052:Reimbursement, Incentive; D012107:Research Design