Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘However, treatment can be given almost immediately, few physicians wouldwithhold treatment for this condition, and few patients would wish to remainuntreated. This shows that economic analyses are not necessarily valuable inisolation. For this reason, other economic endpoints are being reviewed, such asthe amount that patients would be willing to pay to avoid such an event.ConclusionAs trial designs evolve, endpoints are becoming more complex. There areoften both primary and secondary endpoints in a trial. Endpoints may consist ofmore than one clinical outcome and can also include biochemical outcomes.Surrogate endpoints are particularly useful for early-stage trials, once it hasbeen established that the surrogate marker is strongly related to the clinicaloutcome for the disease process. Economic outcomes are becoming moreimportant and are now more frequently evaluated. Given all these choices, it iswise to appreciate the strengths and limitations of each type of endpoint at anearly stage of study design.References1. Temple RJ. A regulatory authority’s opinion about surrogate endpoints. In: Nimmo WS, Tucker GT,editors. Clinical Measurement in Drug Evaluation. New York: John Wiley & Sons, 1995:3–22.2. Mwaba P, Mwansa J, Chintu C, et al. Clinical presentation, natural history, and cumulative deathrates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated underlocal conditions. Postgrad Med J 2001;77:769–73.3. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients withacute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502.4. Spilker B. Guide to Clinical Trials. New York: Raven Press, 1991.5. Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled?Ann Intern Med 1996;125:605–13.6. Greenhalgh T. How to read a paper. Papers that report drug trials. BMJ 1997;315:480–3.7. Preliminary report: Effect of encainide and flecainide on mortality in a randomized trial ofarrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial(CAST) Investigators. N Engl J Med 1989;321:406–12.8. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients receiving encainide,flecainide or placebo. The Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991;324:781–8.9. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction.The Cardiac Arrhythmia Suppression Trial II Investigators. N Engl J Med 1992;327:227–33.10. Smith R. New BMJ policy on economic evaluations. BMJ 2002;325:1124.11. Patrick DL, Erickson P. Health Status and Health Policy. Quality of Life in Health Care Evaluationand Resource Allocation. New York: Oxford University Press, 1993.12. Ramsey SD, McIntosh M, Sullivan SD. Design issues for conducting cost-effectiveness analysesalongside clinical trials. Annu Rev Public Health 2001;22:129–41.45