Author Insights: An Analysis Excluding Trials by Researcher Under Fire for Misconduct Finds Product Used for Critically Ill Patients Is Harmful

Ryan Zarychanski, MD, MSc, of the University of Manitoba, and colleagues reported they found no clinical benefit for use of hydroxyethyl starch for fluid resuscitation and found evidence of greater risks associated with this drug compared with alternatives. Image: Daniel Gwozdz, University of Manitoba

Ryan Zarychanski, MD, MSc, of the University of Manitoba, and colleagues reported they found no clinical benefit for use of hydroxyethyl starch for fluid resuscitation and found evidence of greater risks associated with this drug compared with alternatives. Image: Daniel Gwozdz, University of Manitoba

A new analysis has found that hydroxyethyl starch (HES), a fluid product used to help resuscitate critically ill patients, does not improve patient survival and may cause harm, according to results published in JAMA today. The results suggest that alleged scientific misconduct by a German scientist may have skewed previous meta-analyses of studies of the product, making it look safer and more useful.

Conflicting data sparked debate among clinicians about the usefulness of HES, a product derived from plant starch, in fluid resuscitation of critically ill patients. That debate intensified in March 2011 when 14 journal editors published a letter reporting the results of an investigation by a panel convened by a German medical association of Joachim Boldt, MD. The letter noted that the medical association was unable to verify whether 88 of Boldt’s published studies had received proper institutional review board approval, leading to the retraction of these articles. Subsequently, the Ludwigshafen Hospital, where Boldt had worked, reported the investigation found evidence of data fabrication and scientific misconduct associated with 10 journal articles by Boldt. Continue reading

Researchers Say Spin and Bias Sometimes Used to Put Best Face on Breast Cancer Study Findings

Use of bias and spin when reporting negative findings from clinical trials may tip the balance in creating a more positive perception of a treatment that has little or no demonstrated benefit or may downplay serious adverse effects. (Image: pixhook/iStockphoto.com)

Use of bias and spin when reporting negative findings from clinical trials may tip the balance in creating a more positive perception of a treatment that has little or no demonstrated benefit or may downplay serious adverse effects. (Image: pixhook/iStockphoto.com)

Most researchers conducting clinical trials hope their work pays off in positive results demonstrating that an experimental intervention benefits patients. But when a trial produces negative findings that a treatment is not helpful or that it has adverse effects, some investigators mask the disappointing results by selective and biased reporting of the findings, say researchers whose findings appear today in the Annals of Oncology.

The researchers, from the Princess Margaret Cancer Centre and the University of Toronto in Toronto, looked at 164 randomized, controlled, phase 3 clinical trials of breast cancer treatments, the results of which were published between 1995 and 2011. They found 92 to be negative trials, in which the data did not demonstrate that the treatment under study had an effect on the primary end point, a specific event (such as survival or halting disease progression) that is measured at the end of a trial to see whether or not a given treatment works. But in 59% of the negative trials, the researchers used positive findings from secondary end points, which are additional events of interest but which the studies have not been designed specifically to address, to cast the treatment under study in a positive light. Continue reading

Author Insights: Many Devices Approved Without Comparative Effectiveness Data


Rita Redberg, MD, a professor of medicine at the University of California, San Francisco, and colleagues found that many high-risk cardiovascular devices were approved without data on their comparative effectiveness. Image: University of California, San Francisco

About half of high-risk cardiac devices approved by the US Food and Drug Administration (FDA) were approved without comparative data on whether they provide better outcomes than other treatment options, found an analysis published online in JAMA.

Advances in medical technology have led to the emergence of devices such as stents, defibrillators, and mechanical heart valves to support or sustain the life of individuals with cardiovascular conditions. These devices are considered high risk because their implantation may require invasive procedures or because once implanted, they are necessary to sustain life. Because of this, many physicians and patients may be surprised to learn that such FDA-approved devices do not have to meet the same high standards of evidence required for drugs used to treat cardiovascular disease. Companies that seek FDA approval for a drug, for example, must conduct 2 randomized controlled trials to compare the effects of their product with a placebo or with another treatment (a so-called active comparator or active control) for the condition. But device makers are not required to submit study data involving an active control. Continue reading

Author Insights: Studies That Show Large Treatment Effects Are Usually Wrong

An analysis by John P. Ioannidis, MD, DSc, of Stanford University, and colleagues suggests that physicians and patients should view studies that suggest large treatment effects with skepticism. Image: Stanford School of Medicine Office of Communications & Public Affairs

Most medical interventions have modest effects, and studies that suggest big effects are usually small and are eventually proven wrong, according to an analysis of medical studies published in JAMA today.

Studies that appear to demonstrate that a medication or other therapy can have a large effect on health conditions often make headlines and may lead clinicians and patients to embrace these interventions. But a team of researchers recently scoured the medical literature for reports of clinical trials with promising study results to assess the strength of such studies and the durability of their findings. As it turns out, they found that most studies that find a large treatment effect are very small, which increases the odds that the findings are due to chance—and in the long run, the findings of a large effect are usually not validated. Subsequent studies usually show a much more modest effect, the authors found. Additionally, few of these promising trials indicate that the medical intervention under study does much to prolong life; instead, they find that interventions may have a big effect on laboratory measures of health. Continue reading

Author Insights: Slight Dip in Prostate Cancer Screening for Older Men After Recommendations


Joseph S. Ross, MD, MHS, assistant professor of internal medicine at Yale University, and colleagues found that a 2008 recommendation to stop PSA-based prostate cancer screening in older men had only a small effect on screening. Image: Yale University

The rate of prostate cancer screening by testing prostate-specific antigen (PSA) levels among men age 75 years or older declined just 2 percentage points after a 2008 recommendation from the US Preventive Services Task Force (USPSTF) to discontinue such screening in this age group because the benefits were outweighed by the risks for these older patients, according to a study published in the Archives of Internal Medicine today.

Since the 2008 USPSTF recommendation, a growing body of evidence has suggested that routine PSA-based screening for prostate cancer saves few lives and may expose many men to serious and unnecessary harms from follow-up screening or unnecessary treatment. Based on such evidence, in May 2012 the USPSTF recommended an end to PSA-based prostate cancer screening for all men.

It is too soon to gauge the effect of the 2012 recommendation on prostate cancer screening. But a team of researchers has analyzed the effect of the 2008 USPSTF recommendation on PSA-based prostate cancer screening in older men. They found that the rate of screening among men 75 years or older dipped about 2 percentage points from 29.4% prior to the recommendation to 27.8% after the recommendation. The screening rate remained steady in a younger population of men. Continue reading

Little Evidence Available on Whether Universal Screening for Hearing Loss Improves Health Outcomes

Evidence is scant regarding the benefits and harms of universal screening for hearing loss in asymptomatic older adults. (Image: Jacek Oleksinski/iStockphoto.com)

There’s insufficient evidence to assess the balance of benefits and harms of screening for age-related hearing loss in asymptomatic adults aged 50 years or older, says the US Preventive Services Task Force (USPSTF). However, the USPSTF recommendation statement, which appears today in the Annals of Internal Medicine, does not apply to individuals seeking evaluation for perceived hearing problems or for cognitive or affective symptoms that may be related to hearing loss.

Age-related hearing loss is a common health problem that can affect independence, emotional well-being, and quality of life. An estimated 20% to 40% of adults older than 50 years and more than 80% of those 80 years or older have hearing loss. Such loss may be treated in some adults with hearing aids that can improve self-reported hearing, communication, and social functioning.

The USPSTF said there is convincing evidence showing that screening tools can reliably and accurately identify adults with objective hearing loss. The problem is that there are few directly applicable clinical trials to produce rigorous evidence to determine whether screening for hearing loss improves health outcomes in persons who are unaware of hearing loss or have noticed some hearing loss but have not sought care. Continue reading

JAMA Forum: Bill Would Gut Patient-Centered Outcomes Research

Aaron Carroll, MD, MS

Aaron Carroll, MD, MS

Last week, the House Appropriations subcommittee on labor, health and human services, and education approved a spending bill, which moves along this week to the full committee for consideration and possible amendments. Then, it’s on to a vote in the House of Representatives.

The bill is generating a fair amount of attention because it takes some drastic steps with respect to government funding of research. Specifically, per Academy Health: Continue reading