Screening asymptomatic adults for disease does not save lives

Last Updated: 2015-01-22

By Will Boggs MD

NEW YORK (Reuters Health) - For 19 diseases where mortality is a common outcome, screening of asymptomatic adults does not result in reductions in all-cause mortality, according to results of a systematic review and meta-analysis.

"We need to be cognizant of the limitations of the evidence and temper the expectations of people who undergo screening," Dr. John P. A. Ioannidis from Stanford University School of Medicine, Stanford, California told Reuters Health by email. "Some screening tests may well be very effective, but not all screening has equal value, and some proposed screening tests may be worthless and even harmful."

Although a number of screening tests are entrenched in clinical and public health practice, it remains unclear whether recommended screening tests, particularly among asymptomatic adults, have evidence from randomized clinical trials supporting their survival benefits.

Dr. Ioannidis and colleagues evaluated the evidence from 48 randomized controlled trials and 9 meta-analyses on 39 screening tests for 19 diseases (screening is recommended for 6 of them) where mortality is a common outcome.

In meta-analyses, disease-specific mortality was reduced between 16% and 45% for only 4 screening tests: ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer; and fecal occult blood test and flexible sigmoidoscopy for colorectal cancer.

All-cause mortality, however, was not reduced in any of the 10 available estimates from meta-analyses, according to the January 15 International Journal of Epidemiology online report.

Additional screening tests associated with reduced disease-specific mortality in individual trials included visual inspection for cervical cancer, alpha-fetoprotein and ultrasound for hepatocellular cancer, and visual examination for oral cancer.

Although individual trials suggested all-cause mortality benefits for ultrasound for abdominal aortic aneurysm, mammography for breast cancer, and visual examination for cervical cancer, meta-analyses that included the individual trials for ultrasound and mammography showed no all-cause mortality benefits.

"One may argue that a reduction in disease-specific mortality may sometimes be beneficial even in the absence of a reduction in all-cause mortality," the researchers note. "Such an inference would have to consider the relative perception of different types of death by patients (e.g., death by cancer versus death by other cause), and it may entail also some subjectivity."

"To some extent, the overall picture is a bit more pessimistic than I would have thought," Dr. Ioannidis said. "In principle, I believe that prevention is a good idea, so finding out that the evidence base for screening is often weak was quite disappointing."

"Familiarize yourself with the evidence and what it means," he suggested. "This will help convey more accurate messages to the people/patients about screening and its impact."

Dr. Paul G. Shekelle from RAND Corporation, Santa Monica, California, wrote a commentary related to this report. He told Reuters Health by email, "Adding lots of outcome measures to any research study always comes at a price, both economic and in terms of loss to follow-up, since the subjects of that research can get frustrated with having to fill out and respond to multiple outcome measures and simply drop out. So I am not an advocate of throwing everything and the kitchen sink into the study protocol and seeing what sticks."

"But there are certainly outcomes of importance other than all-cause or disease-specific mortality, and these vary on a condition-by-condition basis," he explained. "I think some pre-study work needs to be done to determine what are the outcomes of most interest to the greatest number of patients with a condition, or persons who are at risk of getting the condition, and then some parsimonious set of these measures should be built into the research study."

"The main message for physicians would be to make sure and know the evidence base for the benefits and harms of the proposed screening test," Dr. Shekelle said.

Dr. Shekelle concludes his editorial by suggesting that the evidence presented in this paper "should be considered by anyone contemplating clinical practice guidelines about screening or proposing new screening tests. We have let too much get into routine practice without an adequate evaluation, and once widely disseminated, it can be very difficult to re-orient patient expectations and clinical behaviors to an understanding that a randomized trial comparing screening with no screening is ethically justified."

Dr. Michael LeFevre, chair of the U.S. Preventive Services Task Force (USPSTF), told Reuters Health by email, "The U.S. Preventive Services Task Force recommends screening tests when the evidence is strong enough to be at least moderately certain that the benefits outweigh the harms. Well conducted randomized trials of screening provide the most certainty of the estimate of benefit, and death is certainly the health outcome we most seek to prevent."

"There may, however, be health outcomes of importance to our patients other than death, and there may be unusual circumstance in which we are able to get moderate certainty about benefits and harms without randomized trials," Dr. LeFevre said. "We are certainly supportive of encouraging randomized trials of preventive services that focus on the health outcomes of importance to our patients."

Dr. Fabrizio Stracci, of the University of Perugia and Regional Cancer Registry of Umbria, Perugia, Italy, told Reuters Health by email, "Since influence on overall mortality depends critically on the frequency of causes of death other than the target disease, I believe that all-cause mortality reduction is too stringent a criterion for most health interventions."

"Screening is overused for some diseases and possibly it is perceived as more effective and cost-effective than it is," he said. "However, the role of screening should be considered on a disease specific-basis. "

Dr. Stracci concluded, "The paper has the merit to show that the screening, as a preventive intervention, has limitations. Thus, evidence of efficacy (and absence of harm) should be carefully considered when giving advice on screening. Importantly it is not possible to assume that early diagnosis is always associated with better cure rates and improved health outcomes for all diseases."

Dr. Laurie Elit, of McMaster University, Hamilton, Canada, has published several papers regarding cervical and ovarian cancer screening. She told Reuters Health by email, "Cervical cancer screening whether with low-cost technologies like VIA (visual inspection with acetic acid) in low resource settings or high cost technologies like HPV (human papillomavirus) testing identifies preinvasive disease, which if treated, can prevent cancer or lead to downstaging, which impacts on both disease-specific and all-cause mortality."

The authors report no external funding or disclosures. Dr. Shekelle reports receiving royalties from UpToDate and an honorarium from ECRI for serving on the National Guidelines Clearing House and National Quality Clearing House Committee.

SOURCE: http://bit.ly/1yxzgZW and http://bit.ly/1JdAmNX

Int J Epidemiol 2015.