title: Chemotherapeutic impact on pain and global health-related quality of life in hormone-refractory prostate cancer: Dynamically Modified Outcomes (DYNAMO) analysis of a randomized controlled trial.
abstract: OBJECTIVE
  This paper applies the Dynamically Modified Outcomes (DYNAMO) model to a clinical trial of two chemotherapeutic regimens on global health-related quality of life (GHRQL) in hormone-refractory prostate cancer.
  
  
  METHODS
  DYNAMO identifies the causal influences operating in a clinical trial and their mediation, moderation, and modulation by uncontrolled variables. The Southwest Oncology Group trial S9916 randomized assignment to mitoxantrone plus prednisone (M + P) versus docetaxel plus estramustine (D + E) treatments. In this application, we examine baseline-adjusted impacts of worst pain (McGill Pain Questionnaire) on GHRQL (EORTC Quality of Life Questionnaire-C30) at 10 weeks.
  
  
  RESULTS
  The average treatment levels of pain did not differ, hence, the average mediated effect of treatment on GHRQL was zero. Nonetheless, M + P reduced the impact (the relational outcome) of pain on GHRQL by 54% relative to D + E. Individual variation in the relational outcome (modulation) was of the same magnitude as the average difference between the groups. Performance status moderated the direct effects of treatment, with D + E being more effective in good, but not poor, performance strata.
  
  
  CONCLUSIONS
  The DYNAMO approach comprehensively accounted for treatment effects. Rather than a single average effect, there were three distinct treatment effects: one direct effect for each performance status level and a direct effect on the relationship between pain and GHRQL.
authors.affiliation: Southwest Oncology Group Statistical Center, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. cmoinpou@fhcrc.org
authors.forename: Carol M
authors.initials: CM
authors.lastname: Moinpour
authors.forename: Gary W
authors.initials: GW
authors.lastname: Donaldson
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D015233:Models, Statistical; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D011241:Prednisone / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000150:complications / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D008942:Mitoxantrone; D011241:Prednisone