Does screening asymptomatic adults for disease save lives? Not necessarily, according to a controversial new meta-analysis in the International Journal of Epidemiology (January 15, 2015).
Researchers from the Stanford University School of Medicine looked at randomized controlled trials, including some for oral cancer, and concluded that, in major diseases in which death is a common outcome, few of the currently available screening tests have documented reductions in disease-specific mortality.
Screening for disease is a key component of modern healthcare. However, several popular screening tests have met with controversy, with breast cancer screening for women ages 40 to 49 and prostate cancer screening in healthy men losing their endorsement by the U.S. Preventive Services Task Force, they noted.
The researchers evaluated evidence on 39 screening tests for 19 major diseases from 48 randomized controlled trials (RCTs) and nine meta-analyses from the Cochrane Database of Systematic Reviews and PubMed to find out whether screening asymptomatic adults for major disease led to a decrease in disease-specific and all-cause mortality. Patients were asymptomatic when tested.
Randomized trials were available for 11 diseases (19 tests), including abdominal aortic aneurysm, breast cancer, cervical cancer, colorectal cancer, hepatocellular cancer, lung cancer, oral cancer, ovarian cancer, prostate cancer, type 2 diabetes, and cardiovascular disease.
The researchers found evidence of a reduction in mortality in 30% of the disease-specific mortality estimates and in 11% of the all-cause mortality estimates from the randomised controlled trials they evaluated. In their review, they found that mortality from the disease being screened dropped in three cases: ultrasound for abdominal aortic aneurysm in men, mammography for breast cancer, and fecal occult blood test and flexible sigmoidoscopy for colorectal cancer. But no other tests reduced the number of deaths caused by the disease in the meta-analyses.
John Ioannidis, MD, DSc. Image courtesy of Norbert von der Groeben/Stanford School of Medicine."Our comprehensive overview shows that documented reductions in disease-specific mortality in randomized trials of screening for major diseases are uncommon," senior author John Ioannidis, MD, DSc, said in a statement. "Reductions in all-cause mortality are even more uncommon. This overview offers researchers, policymakers, and healthcare providers a synthesis of RCT evidence on the potential benefits of screening, and we hope that it is timely in the wake of recent controversies."
Dr. Ioannidis is the C.F. Rehnborg Chair in Disease Prevention at Stanford University; a professor of health research and policy, as well as medicine, at Stanford's School of Medicine; and the director of the Stanford Prevention Research Center.
The researchers argue that randomized evidence should be considered on a case-by-case basis, depending on the disease. Screening is likely to be effective and justifiable for a variety of other clinical outcomes besides mortality, they wrote.
The tests might not be able to detect accurately enough early stages of the disease, according to the researchers, or there might not be lifesaving treatments available.
Dr. Ioannidis acknowledged that screening might ward off other ill effects of disease aside from death. But in general, few screening tests among the many new ones being proposed are subjected to a randomized controlled trial before they are introduced, he noted.
"This is unfortunate," Dr. Ioannidis said. "All screening tests should be evaluated with rigorous randomized controlled trials. I see no alternative to prove that they are worth being adopted in large populations."
This work follows another recent paper, in which Dr. Ioannidis and colleagues argued that screening all baby boomers for hepatitis C isn't necessarily beneficial (BMJ, January 13, 2015).
"Our overview suggests that expectations of major benefits in terms of reductions in mortality from screening need to be cautiously tempered," the researchers concluded.
In an accompanying commentary on the Stanford researchers' analyses, also published in the International Journal of Epidemiology, Peter Gøtzsche, director of the Nordic Cochrane Centre in Copenhagen, Denmark, argued that although screening is popular and has "great public and political appeal," we must "demand much stronger evidence" that it is effective.
Paul Shekelle, MD, PhD, of the University of California, Los Angeles, also commented that too much screening has been allowed to get into routine practice without adequate evaluation. However, Dr. Shekelle also pointed out that mortality is not the only outcome, and patients may value screening tests that decrease the risk of serious morbidity.
In a third commentary, Paul Taylor, PhD, of University College London, wrote that "the cautious tempering of expectations advised" by Dr. Ioannidis and colleagues "is prudent but shouldn't be overdone."
