Using a Drug Facts Box to Communicate Drug Benefits and Harms Two Randomized Trials

Context Direct-to-consumer drug advertisements do not provide standardized information about the benefits and harms of drug therapies. Contribution These randomized trials tested whether adding a drug facts box to consumer prescription advertisements improved consumer knowledge and judgment. The facts box showed numbers of outcomes, including adverse events, which might occur with 2 alternative drug therapies. Consumers given advertisements that included the box had more accurate perceptions of drug benefits and side effects than consumers given advertisements without the box. Implication A standardized table quantifying outcomes that might occur with different therapies improved consumer knowledge of drug benefits and side effects. The Editors Direct-to-consumer advertising surpasses all other efforts to alert the U.S. public about prescription drugs. Industry spent more than $5 billion on these ads in 2007 (1)more than twice the total U.S. Food and Drug Administration (FDA) budget (2). Although the ads are often justified as serving an educational purpose, they generally fail to provide the most fundamental information consumers need to make informed decisions: data on how well the drug works. To address this problem, we developed a drug facts box, a 1-page summary of a drug's benefit and side effects. The central information is provided in a table that shows the chance of various outcomes for people who do and do not take the drug. In previous studies, we showed that consumers understand and value this information (3, 4). We performed 2 randomized, controlled trials in nationally representative samples of U.S. adults (the target audience for direct-to-consumer advertising) to test whether a drug facts box improves consumer knowledge and helps people make better choices. Methods Design We conducted 2 randomized, controlled trials with the same basic design from October 2006 through April 2007: the symptom drug box trial and the prevention drug box trial. We conducted a pair of trials because consumers generally face decisions about 2 categories of drugs: those taken to treat current symptoms and those taken to reduce the risk for future events (prevention). In the symptom drug box trial, we used direct-to-consumer ads for drugs to treat heartburn, an outcome (heartburn relief) that is common and experienced directly. We chose to include a proton-pump inhibitor (PPI) and a histamine-2 (H2)blocker because both drugs are used to treat current symptoms of the same disease and have similar side effect profiles, but PPIs clearly outperform H2-blockers; we could therefore assess whether the box helped consumers choose the superior drug. In the prevention drug box trial, we used advertisements for a statin and clopidogrel for secondary cardiovascular prevention. These drugs are used to reduce the risk for future events that are important but relatively rare (heart attack and death), so absolute effects can only be small. The goal of this trial was to see whether the box improved the accuracy of consumers' perceptions about drugs used to reduce cardiovascular risk. Figure 1 shows the ads used in each trial. Figure 1. Advertisements given to trial participants. Appendix 1 and Appendix 2 provide full-size images of all 8 ads. PPI = proton-pump inhibitor. Supplement. Appendix 1 Supplement. Appendix 2 Committees for the protection of human subjects at Dartmouth Medical School and the University of Massachusetts approved the trials. Trial protocols were registered with ClinicalTrials.gov before recruitment began. Sample Selection Figure 2 summarizes participant flow into the study. Figure 2. Study flow diagram. Random-Digit Dialing Protocol The Center for Survey Research, University of Massachusetts (who conducted both surveys), created 2 national, random-digit dial samples, each with about 3000 telephone numbers. Trained interviewers used a standard protocol in which they called each telephone number at least 6 times (different days, weeks, and times). Whenever someone answered, the interviewer explained that we are conducting an important study about how people feel about different ways to provide information about prescription drugs in advertising. English-speaking adults age 35 to 70 years in the household were invited to participate (if >1 adult was eligible, the computerwhich guided these screening interviewsrandomly selected one). Randomization and Mail Survey Protocol Participants were randomly assigned to the drug box or control group by using a central computerized random-number generator (to ensure allocation concealment) and were mailed survey materials (2 drug ads, the survey, and a stamped return envelope) plus a prepaid $10 incentive with a promise of an additional $10 upon survey completion. Participants were not told about the alternate survey form. Nonresponders received reminder postcards after 2 weeks, a replacement questionnaire after 4 weeks, a telephone call after 6 weeks, and a questionnaire after 8 weeks. Response Rates We used standard Association for Public Opinion Research methods to calculate overall response rates (5). The numerator is completed surveys (231 symptom drug box trial participants [122 in the drug box group and 109 in the control group] and 219 prevention drug box trial participants [111 in the drug box group and 108 in the control group]). The denominator is individuals known to be eligible (289 in the symptom drug box trial and 290 in the prevention drug box trial) plus an estimate of eligible individuals in households that could not be screened. In the symptom drug box trial, this number184was calculated by applying the 44.4% eligibility fraction observed among screened households to the 414 unscreened households. The overall response rates were 49% in the symptom drug box trial (231/[289 + 184]) and 46% in the prevention drug box trial (219/[290 + 182]). Completion rates were calculated by using completed surveys as the numerator and participants as the denominator. For the symptom drug box trial, the completion rate was 89% (231/258); the drug box group had a higher completion rate than the control group (95% [122/129] vs. 84% [109/129]; P= 0.010). In the prevention drug box trial, the completion rate was 84% (219/260) and did not differ between groups. Study Materials We modified actual drug ads by disguising the name of the drug and manufacturer to avoid preconceived notions that participants might hold. Appendix 1 and Appendix 2 include all materials. Ad Image Page All participants received the same ad image page (the colorful front page). Participants in the symptom drug box trial received ads for an H2-blocker (Amcid) and a PPI (Maxtor). In the prevention drug box trial, the ads were for a statin (Concor) and clopidogrel (Pridclo). Second Page In both trials, the second page differed according to randomization. For control participants, the second page was the actual ad's brief summary: the drug label excerpt that the FDA requires in drug ads. The drug box groups received drug facts boxes. These boxes (Figure 3 shows the Pridclo [clopidogrel] box) include a descriptive section with basic drug information (such as indications and other things to consider doing). The central element is a summary table of efficacy and side effects presented as the chance of various outcomes for people who do or do not take the drug. We completed the boxes by using data from individual trials because that is how the FDA approaches drug approval; they do not use meta-analysis to judge efficacy. Figure 3. Pridclo (clopidogrel) drug facts box. FDA = U.S. Food and Drug Administration. To find efficacy data for the boxes in the symptom drug box trial, we used the Cochrane Collaboration review (6) on short-term treatment of gastroesophageal reflux diseaselike symptoms to identify all placebo-controlled trials of PPIs and H2-blockers for empirical therapy. For each drug, we chose the largest of the trials with same outcome: sustained relief, which is no heartburn episodes for 3 consecutive days. To facilitate comparisons, we standardized the base rate of sustained relief by averaging the findings in the placebo groups of the 2 studies (23% in the H2-blocker study [7] vs. 15% in the PPI study [8], yielding an average base rate of 19%). We calculated the relative risk (drug vs. placebo) for sustained relief in the H2-blocker (relative risk, 1.87) and PPI (relative risk, 4.67) trials by using the observed findings. To get standardized rates, we multiplied the averaged placebo rate by each relative risk. To frame the outcome as the proportion of patients still having heartburn, we used the complement of these calculated rates. Side effect data for the drug boxes were abstracted from the corresponding brief summaries (given to control participants) to ensure that both groups had access to similar information. Although many side effects are listed throughout the brief summary, the drug box includes only the most important and largest relative to placebo or other comparator (organized into life-threatening and symptom categories) to focus the reader's attention and minimize cognitive burden. To find efficacy data for the boxes in the prevention drug box trial, we began with the currently approved label for clopidogrel (9). The label cites a single trial supporting the use of clopidogrel for heart attack prevention: CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events) (10). To find a similar study for the statin (in terms of sample size, high-risk population, and outcome of heart attack), we reviewed a meta-analysis of cholesterol-lowering treatment (11). We chose the Medical Research Council Heart Protection Study of simvastatin (12). To facilitate comparisons, we standardized the base rates of heart attack and all-cause mortality by taking the average risk in the comparator groups of the 2 studies. To get the standardized risk in both drug groups, we multiplied the standardized base