The positivity assumption and marginal structural models: the example of warfarin use and risk of bleeding.

Estimates of the average causal effect (ACE) of warfarin on the risk of bleeding may be confounded by indication as patients at high risk of bleeding are unlikely to be prescribed warfarin. One approach to estimating the ACE is inverse probability of treatment weighting (IPTW). This study was designed to examine the use of IPTW in this setting, and to demonstrate problems with the violation of the positivity assumption. We analyzed a case-control study on 4,028 cases of gastro-intestinal bleeding and 79,239 controls set in the United Kingdom's General Practice Research Database. Warfarin exposure was defined as a prescription issued in the 90 days before the index date. Secondary analyses were conducted restricted to patients more likely to receive warfarin and with a truncated weight distribution, to exclude subjects highly unlikely to be treated. The estimated association between warfarin use and bleeding was stronger with IPTW [odds ratio (OR): 17.2; 95% confidence interval (CI): 6.5-37.7] than with a standard logistic regression model (OR: 2.1; 95% CI: 1.7-2.5). The presence of large weights (five subjects with stabilized weight >500) indicated a potential violation of the positivity assumption. In the restricted analysis, both IPTW (OR: 2.0; 95% CI: 0.4-9.6) and standard regression (OR: 1.6; 95% CI: 1.3-2.0) were compatible with a meta-analysis of randomized trials inverse probability of treatment weighting is sensitive to the positivity assumption; however, such sensitivity may assist in diagnosing off-support inference.

Assessing a whiplash management model: a population-based non-randomized intervention study.

OBJECTIVE: To evaluate the effectiveness of a multidisciplinary clinical management approach for whiplash-associated disorders (WAD) following a motor vehicle injury in Quebec. METHODS: A clinical management model was implemented in 5 geographic regions of the Province of Quebec, Canada, in 7 hospitals and 19 clinics. A 2-group population-based parallel design was used to assess its effectiveness. All patients with a new whiplash injury seen in these 26 centers between March and September, 2001 were entered into the Whiplash Management Model (experimental group). A reference group included all subjects who had a whiplash injury during this same period but were not seen in these 26 intervention centers. All subjects were followed for up to a year. The outcome variables were time on compensation, time to file closure, and total direct costs. RESULTS: A total of 288 patients with WAD were identified in the experimental group and 1,875 patients in the reference group. The rate of ending of compensation was significantly higher in patients who received the experimental treatment model than those receiving the reference treatment approach (rate ratio, RR: 3.2; 95% confidence interval, CI: 2.8-3.6). The rate of file closure was also significantly higher with the experimental treatment (RR: 1.5; 95% CI: 1.2-1.8). The average cost per patient was significantly reduced with the experimental intervention. CONCLUSION: A coordinated whiplash management approach can lead to earlier return to work and lower costs for patients who have sustained a whiplash injury.