IV methods61 which may control for these unmeasured confounders and which have been widely used in econometrics,62-63 have yet to be applied to the study of comparative effectiveness of OP medications.
IV methods estimate the treatment effect adjusting for unmeasured confounding in observational studies. These methods are widely used in econometrics. IV methods depend on the existence of an
20
instrumental variable (i.e., “instrument”). Prior pharmacoepidemiologic studies using IV methods based on administrative databases have used a variety of co-Rxs, comorbidities, and other variables as instruments.64-69, 25
Generally, the IV estimate is the intent-to-treat estimate of the effect of the IV (numerator) on the treatment on the outcome, weighted by the strength of the IV in predicting received treatment
(denominator).62
where X is received treatment, Y is outcome, and Z is IV.
Figure 2.1. Directed acyclic graph of IV, treatment, confounders and outcome illustrating the main assumptions of IV methods.
IV methods rest on three main assumptions: (1) the IV is associated with the received treatment (i.e., the IV affects the treatment choice or shares a common cause with it), (2) covariate values do not differ by the level of the IV (independence assumption), and (3) the IV does not predict the outcome except through its influence on the treatment (exclusion restriction; no direct effect of the IV on the outcome and no effect of any kind of the outcome on the IV).69
Evidence of physician/provider preference for osteoporosis medications
The decision to prescribe one OP drug over another may depend on several factors such as convenience, drug tolerance, and adherence to dosing schedules.28, 29 The preference-based IV
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assumes that physicians or groups of providers differ in their preferences for medical treatments or procedures for similar patients.70 Differences in hospital capacity, drug benefit plans or formularies may lead to regional differences in medical decision making among groups of physicians.71 Other factors such as marketing by pharmaceutical companies, a physician’s clinical experience, emerging evidence about safety and efficacy of a drug, patient case mix, drug availability and reimbursement may also influence a physician’s prescribing decision. However, as long as these factors contributing to physician prescribing decisions are not related to patients’ characteristics, the assumptions of the IV are not violated.
Furthermore, for OP medications, a physician’s prescribing preferences may be influenced by patient preference which may depend on affordability,28 potential side effects,72, 73 convenience of dosing schedule,29 and route of administration.74 If these patient preferences are associated with potential confounding variables, the validity of the IV may be compromised.
The most widely prescribed OP medications are BP, which are potent antiresorptive drugs that slow or prevent the dissolving of bone thereby maintaining or increasing bone strength.32 BP have been associated with safety concerns including osteonecrosis of the jaw51 and atypical femoral Fx.8 Another OP medication, teriparatide, a parathyroid hormone and anabolic drug, increases the rate of bone formation and thus rebuilds bone.75 We hypothesized that physicians would differ in their Rx preferences for OP medications and hence chose to evaluate physician preference for prescribing BP versus other OP medications as a potential IV.
22 REFERENCES
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CHAPTER III. METHODS