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Another key component of the study i nvolve d a s ses si ng t he nu mb ers of patients who were eligible for clinical tria l pa r ticipation but not enrolled. Researchers found participation was "infrequent" and steadily declined. At the end of the 2008–2011 study period, only 3.4 percent of eligible patients were enrolled in trials at 255 sites, even though most patients with myocardial infarction were eligible for a trial. "We found that two-thirds of these patients were eligible, and that suggests we could do a better job to make sure the people who are in our clinical trials are more representative of the people we're treating in routine practice," says the lead author of the study, Jacob A. Udell, MD, MPH, Assistant Professor in the Department of Medicine at the University of Toronto. Valid but … Even t hough t r ia l result s may be ba sed on a v a r ia nt of t he t a rgeted patient population, that doesn't mean treatments aren't effective. "The trials will always be valid — they're randomized treatment comparisons, so there are no confounding [variables] there …," Dr. Udell notes. "The question is whet her or not [t he res u lt s] a re accentuated or muffl ed in people in the real world." A n d i n t h e r e a l w orld , p a t ie nt s a re of t en sic k er a n d pre s ent w it h more comorbidities. "This is a matter of concern because ultimately, the way we should define standards of care is by what's shown in large-scale, rigorous clinical trials," says Michael Lauer, MD, Director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute. "So, as much as possible, we'd like to make those trials as representative of the population of patients physicians see in clinical practice as we can." Guidelines for prescribing medication in clinical practice are less stringent than in clinical trials, so there is the possibility that patients may benefit less or even be harmed by medications tested in clinical research and deemed effective, Dr. Udell says. He doesn't think physicians should sound the alarm based on his research, but he does urge caution. For example, he recommends that before prescribing medications, physicians should consider whet her pat ient s wou ld h ave b e en el i g ible t o p a r t ic ip a t e i n t he t r i a l v a l id a t i n g t h a t m e d ic a t ion i n t h e fi rst place. That can shed light on the drugs' potential effectiveness for those particular patients. A Call to Action Dr. Udell sees low enrollment rates in clinical trials as a direct challenge to physicians. "I think [the study] is a wa ke-up call," he says. "I hope [it's] a calling for physicians wanting to get more involved in clinica l tria ls to enroll patients at their own clinical site or hospital practices. Then we'd all feel more confi dent in the data." Dr. Lauer says it's a matter of paying it forward, just as previous generations of physicians did. "Because [physicians] are able to provide better care for patients by virtue of the fact that clinical research has been done before by other physicians, we should aspire to an environment where all clinicians see it as an integral part of their being that they would participate and engage in the enterprise of clinical research," he says. ■ G E T TI N G IT R I G H T THE GRUPPO ITALIANO per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI) series of clinical trials stands as a methodological landmark and serves as a how-to manual for recruiting patients for large-scale clinical trials. In the four GISSI studies, more than 60,000 patients who had experienced myocardial infarction have been recruited over a 20-year period. Because clinical trial participants frequently don't represent the overall patient population, experts say, measures should be taken to increase the generalizability of the trials. "The way to [conduct a representative trial] is to embed clinical trials into routine clinical care," says Michael Lauer, MD, Director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute. "Ideally, you do it in such a way that every single patient who has a condition is considered a viable candidate for participating in a clinical trial." That's precisely what GISSI achieved. In GISSI 1, physicians across northern Italy agreed to encourage patient participation in a trial that tested whether streptokinase improved survival among people suffering acute myocardial infarction. Physicians enrolled approximately 12,000 patients in 17 months and demonstrated that streptokinase did reduce the mortality rate. LESSONS FROM PEDIATRICS Such success has also been seen domestically in pediatric cancer care. For decades, children in the United States have been enrolled in clinical trials as a routine part of treatment. "Basically, the care of kids with cancer meant [they] participated in clinical trials," Dr. Lauer says. "That means you don't have to worry if the population is representative because you actually study the population that matters." M D N E W S . CO M ■ MD NEWS Minnesota | 1 3

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