New study details increased international participation in US NHLBI-sponsored cardiovascular trials; further scrutiny warranted

National Heart, Lung, and Blood Institute (NHLBI)- sponsored cardiovascular (CV) trials often enroll a "substantial" proportion of international participants, according to a new analysis published recently in the Journal of the American College of Cardiology.

"The decreased US participation in NHLBI CV trials is cause for concern," the investigators stressed in their paper. They continued on to caution how increased international participation in such clinical trials could result in poorer generalizability (external validity) of the trials' results to US patients and decrease US prescriber acceptance of the research findings.

For their analysis, investigators searched the National Institutes of Health's (NIH) registry of clinical trials to identify randomized phase 3 or phase 4 CV trials funded by the NHLBI between 1997 and 2009. They identified a total of 24 studies, 19 (79%) of which included international participants (total number of international participants in these trials was 151,682 or ~15% of all participants). The median proportion of international enrollment in all trials was 9.5%, but exceeded three-quarters of patients in 4 trials. Of note, high-risk CV trials and trials testing acute interventions tended to have higher rates of international participation, with coronary artery disease trials (n=11 studies) having a median international participant enrollment rate of about 50% compared to 0.3% to 15.8% in the other CV trials.

IMPACT ON PATIENT CARE

The investigators noted, "The results of these studies profoundly influence patient care both in the United States and worldwide and universally result in Class 1 recommendations in the American College of Cardiology and American Heart Association treatment guidelines."

NHLBI-sponsored trials that have enrolled international participants are likely familiar to most, and include such influential trials as ALLHAT (for hypertension), AFFIRM (for atrial fibrillation), ACCORD (diabetes), PEACE (stable coronary artery disease), and SCD-HeFT (internal cardioverter defibrillators). Each of the trials was published in a respected medical journal including NEJM, JAMA, Lancet, Circulation, or JACC.

"Given questions of applicability and ethical and financial considerations, international participation in US clinical trials deserves further scrutiny," concluded the investigators.

SOURCE

Kim ESH, Carrigan TP, Menon VM. International participation in cardiovascular randomized controlled trials sponsored by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2011; 58:671–676.