TABLE 4.
Association Between Formulary Changes and Black Box Warning Characteristics in Difference-in-Differences Exploratory Subgroup Analyses
| Black Box Warning Characteristicsa | 1 Year After BBW Difference-in-Differences Estimate, Adjusted Analysis (95% CI)b, % | P Valuec | 2 Years After BBW Difference-in-Differences Estimate, Adjusted Analysis (95% CI)b, % | P Valued |
|---|---|---|---|---|
| Classification | ||||
| New BBW (n = 35) | −0.63 (−18.1-16.9) | 0.94 | −2.4 (−20.2-15.3) | 0.79 |
| Major update to preexisting BBW (n = 66) | −4.3 (−17.2-8.5) | 0.51 | −5.8 (−18.8-7.2) | 0.38 |
| Patient population affected | ||||
| General (n = 42) | −5.4 (−22.3-11.4) | 0.53 | −6.0 (−23.1-11.2) | 0.50 |
| Specific population (n = 30) | −1.1 (−19.5-17.2) | 0.90 | −3.1 (−21.9-15.8) | 0.75 |
| General population with higher risk in specific population (n = 29) | −1.6 (−20.4-17.2) | 0.87 | −4.3 (−23.1-14.5) | 0.65 |
| Class warning | ||||
| Included in class warning (n = 47) | −0.1 (−15.6-15.3) | 0.99 | −1.4 (−16.8-14.0) | 0.86 |
| Not included in class warning (n = 54) | −5.6 (−19.8-8.5) | 0.44 | −7.4 (−22.0-7.1) | 0.32 |
| REMS | ||||
| BBW accompanied by ETASU REMS or ETASU REMS already in place (n = 17) | −6.8 (−33.1-19.4) | 0.61 | −5.8 (−32.4-20.8) | 0.67 |
| No ETASU REMS before or in association with BBW (n = 84) | −2.3 (−13.5-9.0) | 0.69 | −4.4 (−15.8-7.1) | 0.45 |
aBecause each BBW drug was matched to a single control drug, the number of drugs in each group was identical. For example, in the new BBW analysis, there were 35 BBW drugs and 35 control drugs.
bCovariates used in adjusted analysis were expected duration of use, therapeutic class, inclusion in a combination product, and availability of alternatives.
cP value represents difference-in-differences analysis of 1 year after BBW versus before BBW, measuring change in mean proportion of formularies providing unrestrictive coverage for BBW drugs compared with control drugs.
dP value represents difference-in-differences analysis of 2 years after BBW versus before BBW, measuring change in mean proportion of formularies providing unrestrictive coverage for BBW drugs compared with control drugs.
BBW = black box warning; CI = confidence interval; ETASU = Elements to Assure Safe Use; REMS = Risk Evaluation and Mitigation Strategies.