title: Physician's Prescribing Preference as an Instrumental Variable: Exploring Assumptions Using Survey Data.
abstract: BACKGROUND
  Physician's prescribing preference is increasingly used as an instrumental variable in studies of therapeutic effects. However, differences in prescribing patterns among physicians may reflect differences in preferences or in case-mix. Furthermore, there is debate regarding the possible assumptions for point estimation using physician's preference as an instrument.
  
  
  METHODS
  A survey was sent to general practitioners (GPs) in The Netherlands, the United Kingdom, New Zealand, Ireland, Switzerland, and Germany, asking whether they would prescribe levothyroxine to eight fictitious patients with subclinical hypothyroidism. We investigated (1) whether variation in physician's preference was observable and to what extent it was explained by characteristics of GPs and their patient populations and (2) whether the data were compatible with deterministic and stochastic monotonicity assumptions.
  
  
  RESULTS
  Levothyroxine prescriptions varied substantially among the 526 responding GPs. Between-GP variance in levothyroxine prescriptions (logit scale) was 9.9 (95% confidence interval: 8.0, 12) in the initial mixed effects logistic model, 8.3 (6.7, 10) after adding a fixed effect for country and 8.2 (6.6, 10) after adding GP characteristics. The occurring prescription patterns falsified the deterministic monotonicity assumption. All cases in all countries were more likely to receive levothyroxine if a different case of the same GP received levothyroxine, which is compatible with the stochastic monotonicity assumption. The data were incompatible with this assumption for a different definition of the instrument.
  
  
  CONCLUSIONS
  Our study supports the existence of physician's preference as a determinant in treatment decisions. Deterministic monotonicity will generally not be plausible for physician's preference as an instrument. Depending on the definition of the instrument, stochastic monotonicity may be plausible.
authors.affiliation: From the aDepartment of Clinical Epidemiology, bDepartment of Medical Statistics and Bioinformatics, cDepartment of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands; dDepartment of Clinical Epidemiology, Aarhus Medical Centre, Aarhus, Denmark; eBern Institute of General Practice, University of Bern, Bern, Switzerland; fDepartment of Epidemiology and Public Health, University College Cork, Cork, Ireland; gDepartment of General Practice and Primary Health Care, University of Auckland, Auckland, New Zealand; hArthritis Research UK Primary Care Centre, Keele University, Keele, Staffordshire, United Kingdom; iInstitute for Evidence-based Medicine in Old age (IEMO), Leiden, The Netherlands; jDepartment of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands; kInstitute of General Practice, Johann Wolfgang Goethe University, Frankfurt, Germany; lDepartment of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland; mInstitute of General Practice and Health Services Research, University of Zürich, Zürich, Switzerland; nDepartment of Primary and Community Care, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; oDepartment of Internal Medicine, University Hospital of Zürich, Zürich, Switzerland; pDepartment of Public Health and Primary Care, Leiden University Medical Centre, Leiden, The Netherlands; and qResearch department of Primary Care and Population health, University College London, United Kingdom.
authors.forename: Anna G C
authors.initials: AG
authors.lastname: Boef
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: Peter
authors.initials: P
authors.lastname: Frey
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Kearney
authors.forename: Ngaire
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authors.lastname: Kerse
authors.forename: Christian D
authors.initials: CD
authors.lastname: Mallen
authors.forename: Vera J C
authors.initials: VJ
authors.lastname: McCarthy
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.forename: Christiane
authors.initials: C
authors.lastname: Muth
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosemann
authors.forename: Audrey
authors.initials: A
authors.lastname: Russell
authors.forename: Henk
authors.initials: H
authors.lastname: Schers
authors.forename: Vanessa
authors.initials: V
authors.lastname: Virgini
authors.forename: Margot W M
authors.initials: MW
authors.lastname: de Waal
authors.forename: Alex
authors.initials: A
authors.lastname: Warner
authors.forename: Jacobijn
authors.initials: J
authors.lastname: Gussekloo
authors.forename: Wendy P J
authors.initials: WP
authors.lastname: den Elzen
mesh_terms: D005260:Female; D058005:General Practitioners; D005858:Germany; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D007494:Ireland; D016015:Logistic Models; D008297:Male; D009426:Netherlands; D009520:New Zealand; D010818:Practice Patterns, Physicians'; D011795:Surveys and Questionnaires; D013557:Switzerland; D013974:Thyroxine / Q000627:therapeutic use*; D006113:United Kingdom
chemical_list: D013974:Thyroxine