title: Rethinking composite end points in clinical trials: insights from patients and trialists.
abstract: BACKGROUND
  Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers.
  
  
  RESULTS
  We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 "spending weights" across 5 common adverse events comprising composite end points in cardiovascular trials: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant's ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons).
  
  
  CONCLUSIONS
  Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.). jstolker@yahoo.com.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Stolker
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: John A
authors.initials: JA
authors.lastname: Spertus
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: David J
authors.initials: DJ
authors.lastname: Cohen
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: Philip G
authors.initials: PG
authors.lastname: Jones
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: Kaushik K
authors.initials: KK
authors.lastname: Jain
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: Emily
authors.initials: E
authors.lastname: Bamberger
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: Brady B
authors.initials: BB
authors.lastname: Lonergan
authors.affiliation: From Saint Louis University, St. Louis, MO (J.M.S., K.K.J.); University of Missouri-Kansas City, Kansas City (J.A.S., D.J.C., E.B., B.B.L., P.S.C.); and Saint Luke's Mid America Heart and Vascular Institute; Kansas City, MO (D.J.C., P.G.J., P.S.C.).
authors.forename: Paul S
authors.initials: PS
authors.lastname: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000401:mortality / Q000517:prevention & control; D002986:Clinical Trials as Topic / Q000523:psychology*; D003625:Data Collection; D023381:Endpoint Determination / Q000523:psychology*; D005260:Female; D006282:Health Personnel / Q000523:psychology*; D006760:Hospitalization; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D057240:Patient Preference; D018802:Patient-Centered Care; D010361:Patients / Q000523:psychology*; D062645:Percutaneous Coronary Intervention; D012307:Risk Factors; D020521:Stroke / Q000401:mortality / Q000517:prevention & control
keywords: cardiovascular diseases; clinical trial; end point determination; patient preference; patient-centered care; statistics