To identify what psychiatrists and other physicians may need to know about recent studies in internal medicine, Monique Yohanan, MD, MPH--a physician editor at Epocrates, Inc-- reviewed several articles published during the last year that she considers newsworthy and most likely to influence clinical practice. Dr Yohanan is board-certified in internal medicine, geriatrics, and hospice and palliative care.
In a well-attended presentation at the American Psychiatric Association’s recent annual meeting, Yohanan listed articles with a “special focus on topics common to patients with comorbid psychiatric and medical illness.”
Yohanan selected a study by Bourgeois and colleagues’ study on drug trial outcome reporting.1 The researchers described characteristics of drug trials listed in www.ClinicalTrials.gov and examined whether the funding source of these trials is associated with favorable published outcomes. They looked at safety and efficacy trials conducted between 2000 and 2006 for antidepressants and antipsychotics as well as anticholesteremics, proton-pump inhibitors, and vasodilators.
Of 546 drug trials, 346 (63%) were primarily funded by industry; 74 (14%) were funded by government sources and 126 (23%) were funded by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials.
Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or non-federal organization-funded trials (P < 0.001). Trials funded by nonprofit or non-federal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs 61.2%; P = 0.013). The researchers concluded that as regards registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.
The issue of stopping clinical trials early, according to Yohanan, was explored in de Lorgeril and colleagues’2 revisiting of the JUPITER (Justification for the Use of Statins in Primary Prevention) trial and in Bassler and colleagues’3 article, which concluded that truncated randomized controlled trials were associated with greater effect sizes than RCTs not stopped early.
Screening and treatment studies
Yohanan also discussed:
o A study of the effects of mammography screening on breast cancer mortality by Kalager and colleagues.4
o A meta-analysis of 6 randomized controlled trials of prostate cancer screening involving 387,286 asymptomatic men by Djulbegovic et al.5
o Risks for false-positive results on lung cancer screening tests by Croswell.6
o The use of rosiglitazone (Avandia) or pioglitazone (Actos) for diabetes, and the risk of acute myocardial infarction and other adverse events as studied by Graham and associates.7
o An updated meta-analysis of rosiglitazone studies by Nissen and coworkers.8
Pointing to the high prevalence of type 2 diabetes and the need for better treatment approaches, Yohanan reviewed 4 journal articles on the ACCORD (Action to Control Cardiovascular Risk in Diabetes) clinical trial.9-12 The trial included 10,251 participants, making it one of the largest studies ever conducted in adults with type 2 diabetes. Because patients with type 2 diabetes are at high risk for such cardiovascular events as heart attack and stroke, the trial tested 3 possible treatment methods for lowering the risk.
Yohanan ended her presentation with a discussion of inflammatory factors,13,14 vitamins and supplements (covered in an earlier article15), and the effects of omega-3 fatty acids on cardiovascular disease.16-18
1. Bourgeois FT, Murthy S, Mandl KD. Outcome reporting among drug trials registered in ClinicalTrials.gov. Ann Intern Med. 2010;153:158-166.
2. de Lorgeril M, Salen P, Abramson J, et al. Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal.
Arch Intern Med. 2010;170:1032-1036.
3. Bassler D, Briel M, Montori VM, et al. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.
4. Kalager M, Zelen M, Langmark F, Adami HO. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363:1203-1210.
5. Djulbegovic M, Beyth RJ, Neuberger MM, et al. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ. 2010;341:c4543.
6. Croswell JM, Baker SG, Marcus PM, et al. Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial. Ann Intern Med. 2010;152:505-512, Erratum in: Ann Intern Med. 2010;152:759.
7. Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304:411-418.
8. Nissen SE, Wolski K. Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170:1191-1201.
9. Ismail-Beigi F, Craven T, Banerji MA, et al.; ACCORD trial group. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419-430. Erratum in: Lancet. 2010;376:1466.
10. ACCORD Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-1585.
11. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010;304:61-68.
12. ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563-1574. Erratum in: N Engl J Med. 2010;362(18):1748.
13. Heart Protection Study Collaborative Group, Emberson J, Bennett D, et al. C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study. Lancet. 2011;377:469-476.
14. Chen E, Miller GE, Kobor MS, Cole SW. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood. Mol Psychiatry. 2010 [Published online May 18, 2010.]
15. Kaplan A. Top medical articles of 2010: Three on vitamins and supplements. Psychiatric Times. Available at: http://www.psychiatrictimes.com/conference-reports/apa2011/content/artic.... Accessed May 24, 2011.
16. Kromhout D, Giltay EJ, Geleijnse JM; Alpha Omega Trial Group. omega-3 fatty acids and cardiovascular events after myocardial infarction.
N Engl J Med. 2010 Nov 18;363:2015-2026.
17. Galan P, Kesse-Guyot E, Czernichow S, et al. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ. 2010;341:c6273.
18. Kowey PR, Reiffel JA, Ellenbogen KA, et al. Efficacy and safety of prescription omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: a randomized controlled trial. JAMA. 2010;304:2363-2372.