Application of lag-time into exposure definitions to control for protopathic bias.

PURPOSE: To control for protopathic bias, some studies have incorporated the concept of lag-time into their exposure definition (time period before the index date that was not considered in assessing exposure). The objective of this study was to introduce a procedure to identify the best lag-time to be applied in studies where control for protopathic bias is required. METHODS: We used data from a case-control study carried out to assess the association between exposure to proton pump inhibitors (PPIs) and risk of gastric cancer, using RAMQ databases. Exposure was defined as the number of defined daily doses of PPIs dispensed during the 5-year period prior to the index date (divided into four quartiles). Thirty-one different lag-times were applied (0-30 months) based on 1-month intervals. Logistic regression was used to estimate the matched odds ratio (OR) for each lag-time. The change point in the ln(ORs) was identified by applying a two-compartmental model and a segmented regression model. RESULTS: A trend of decreasing ORs was found with the application of an increasing lag-time. As an illustration, the ORs for the 1st quartile of defined daily doses, when applying the 31 different lag-times, ranged between 3.52 when applying a 0 lag-time and 0.97 when applying a 30 months lag-time. Applying the two methods for the different lag-times showed that the ORs stabilized at around 6 months. CONCLUSION: For the purpose of controlling for protopathic bias in pharmacoepidemiological studies, we have provided a method to assess the most appropriate lag-time that should be applied for the assessment of drug exposure.

Assessment of Canadian provincial expenditures in depressed patients treated with venlafaxine XR versus SSRIs: the APEX Study.

OBJECTIVE: Empirical studies of antidepressant cost-effectiveness suggest that the use of venlafaxine may be no more costly than selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. The objectives of this study were to identify patients' characteristics and factors associated with the choice of antidepressant and to assess differences in persistence, healthcare utilization and direct medical costs associated with venlafaxine and SSRIs pharmacotherapy. RESEARCH DESIGN AND METHODS: We examined demographic and clinical characteristics of patients (n = 17 144) who received both a diagnosis of depression and a prescription for venlafaxine or an SSRI between 1996 and 2004 using the Quebec health administrative databases. Logistic regression models were used to identify factors independently associated with the choice of antidepressant. Persistence to treatment and overall direct medical costs during 12 months after initiation of therapy were assessed using Cox proportional hazard and GLM models, respectively. RESULTS: Age, sex, provider specialty, and prior 12-month healthcare utilization significantly influenced initial antidepressant choice. Fewer venlafaxine-treated patients discontinued their initial therapy relative to SSRIs' (persistence to initial treatment: 38.4% vs. 29.4% and 24.4% vs. 15.8% at 6 and 12 months, respectively; p < 0.0001), and they were less likely to require treatment switching. Overall 12-month direct medical costs for SSRI- and venlafaxine-treated patients were Can$2759 and Can$2604, respectively. Patients treated with SSRIs had significantly higher expenditures in a univariate analysis (cost ratio: 1.06 [95% CI: 1.02, 1.10]). However, after controlling for potential confounding factors such as patients' characteristics, prior healthcare utilization, and comorbid conditions in multivariate analyses, the overall expenditures were similar in both groups (cost ratio: 1.03 [95% CI: 0.99, 1.07]). CONCLUSIONS: Direct medical costs were generally similar among patients with depression treated with venlafaxine and SSRIs. In a 'real world' setting, the higher acquisition cost of venlafaxine is offset by savings due to fewer hospitalizations and fewer outpatient medical visits. Differences in treatment persistence may also, in part, explain the observed differences in average direct medical costs between venlafaxine and SSRIs.