title: The placebo effect in thyroid cancer: a meta-analysis.
abstract: BACKGROUND
  The natural history of advanced thyroid malignancies is largely unknown. The outcome of patients included in the placebo arm of clinical trials could be reflective of their therapy-free evolution.
  
  
  OBJECTIVE
  To analyze the response rate, symptoms and adverse effects of locally advanced or metastatic differentiated (DTC) and medullary thyroid cancer (MTC) in patients treated with placebo in clinical trials.
  
  
  METHODS
  PubMed (MEDLINE) and SCOPUS databases were searched through September 2015 to identify high-quality randomized controlled clinical trials. We included studies that recruited patients with DTC or MTC with a placebo arm.
  
  
  METHODS
  We conducted a meta-analysis for each category of response rate, adherence to treatment, and adverse events. An empirical Bayesian random-effect model was used.
  
  
  RESULTS
  We identified five clinical trials. DTC and MTC were independently analyzed. In the placebo arm, no complete response was observed; partial response occurred in 1.6% (0.6-3) and 6.4% (3.4-10.3) of DTC and MTC respectively; stable disease was described in 40.5% (34.6-46.9) and 53.9% (44.3-64.4) of DTC and MTC respectively. DTC reached a disease control rate of 42.3% (36.2-48.9) and MTC of 60.2 (50.1-71.4). Treatment discontinuation rate was 3.5% (1.9-5.5) in DTC and 5.7% (3.0-9.4) in MTC. Rate of dose reduction was 7.3% (4.8-10.5) in DTC and 6.2% (3.3-10.0) in MTC.
  
  
  CONCLUSIONS
  This meta-analysis provides extensive data on the response rate and adverse effects of locally advanced or metastatic DTC and MTC in patients treated with placebo. These results may be used for comparisons with results from clinical trials without a placebo arm.
authors.affiliation: Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Llavero-Valero
authors.affiliation: Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Guillén-Grima
authors.affiliation: Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Zafon
authors.affiliation: Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain jcgalofre@unav.es.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Galofré
mesh_terms: D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000453:epidemiology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000453:epidemiology* / Q000473:pathology; D016896:Treatment Outcome; D016903:Drug Monitoring