Cancer data: Burying bad news

[Guest guest]

Cancer data: Burying bad news by Janet Raloff

 

http://www.sciencenews.org/view/generic/id/36805/title/Cancer_data_Burying_bad_n\

ews

 

When doctors are looking to treat an illness, they often rely on

reports in medical journals. Sometimes those reports describe striking

successes with a particular therapy. Less frequently, they highlight

failures. To physicians, learning what doesn't work or has troubling

side effects can be as important as knowing which therapies hit a home

run.

 

Yet doctors — and the reporters who highlight research news — are

getting a very skewed picture of research findings if they rely on

what makes it into major medical journals.

 

The reason: Data from fewer than one in five research trials are ever

published. Findings from the vast majority of human trials become

buried for reasons that may never come to light, according to a new

study in The Oncologist. It's published early and online September 24.

 

For the past nine years, the National Institutes of Health have

maintained a registry of medical trials. Researchers must list theirs

with this ClinicalTrials.gov registry. If they don't, major medical

journals (those that belong to the International Committee of Medical

Journal Editors) will not publish the trial's findings.

 

Scott Ramsey and John Scoggins of the University of Washington,

Seattle, scoured that registry for any trial that was supposed to have

been conducted to gauge the effectiveness of cancer treatments — and

turned up 2,028. The pair then cross-checked these trials against all

published studies that were listed in PubMed, a comprehensive database

compiled by the National Library of Medicine. PubMed includes

citations to all medical and related studies that have been published

in peer-reviewed journals.

 

Among the cancer trials that were identified as completed or halted as

of a year ago, just 17.6 percent were ultimately published in

PubMed-listed journals, Ramsey and Scoggins report.

 

Okay, maybe the halted trials were pulled because of what turned out

to be poor research design, failure to recruit enough patients, or

some other reasonable issue. But even after restricting the analysis

to only those trials that were completed, the share that ended up

being published still amounted to fewer than one in five.

 

Who conducted a trial seemed to influence the likelihood its data

would see the light of day. Studies sponsored by industry (such as

drug companies) had the lowest publication rate: 5.9 percent. By

comparison, data from 59 percent of studies performed by

clinical-trial networks were published.

 

Ramsey and Scoggins turned up 341 cancer trials from the registry that

were published. Of these, two-thirds reported positive — expected and

beneficial — findings.

 

The new analysis raises the ugly specter of publication bias, its

authors say. The assumption is that many if not most unpublished

trials involved treatments that didn't work. " Of particular concern, "

they argue, is the especially poor showing by industry-sponsored

trials, since they tended to probe the value of patented drugs — " many

of which are in clinical use. "

 

James H. Doroshow, director of the National Cancer Institute's

division of treatment and diagnosis, notes that last year alone some

50,000 patients took part in trials that his institute funded. The

" apparent lack of access to the final efficacy and toxicity data for

cancer clinical trials from all sponsors, but especially for

industry-sponsored studies, poses multiple scientific and ethical

questions, " he charges in an editorial accompanying the new paper.

 

For instance, as doctors begin developing novel chemotherapy cocktails

— mixtures of drugs initially tested on their own — toxic reactions

may emerge. It's imperative, Doroshow says, that inklings of such side

effects be communicated immediately " to the entire oncology community

in the peer-reviewed literature. "

 

Moreover, he notes that some drug-safety trials did not publish their

findings, or did not do so early enough, such that they could inform

subsequent trials. This practice is not likely to continue, he points

out, since new federal rules will fine investigators who fail to post

outcome data for all trials getting money from Uncle Sam. Moreover,

for cancer trials, NCI will require that researchers begin reporting

outcome data — treatment successes and failures — throughout the

course of the trial, not just at the end.

 

A second editorial, this one by The Oncologist's senior editor,

Gregory A. Curt (an employee of drug company AstraZeneca), and

editor-in-chief Bruce A. Chabner (of Harvard Medical School) find the

new analysis by Ramsey and Scoggins " thought-provoking and

disturbing. " At a minimum, they argue, publication of trial data

should be considered " an obligation " for any researchers recruiting

patients who contribute " their precious time and well-being, and for

some, their very lives. "

 

This is especially true for drug-company trials, they contend, since

" industry has become the dominant sponsor of new drug trials. "

 

But Curt and Chabner also suspect that part of the problem illustrated

in the new paper traces to issues other than a drug company's interest

in hiding bad data.

 

For instance, study authors " face the hurdle of finding a journal

willing to publish a negative, poorly designed or inadequately

accruing trial. " This is especially true, they say, since " Journals

live and die based on their Impact Factor " — how often they're cited

by subsequent papers. Any journal filled with such findings would " not

attract readership, citations and advertisement, " they write.

 

One solution Curt and Chabner propose: Make NCI funding for new trials

dependent on the investigators' past track record of getting their

trials data — both positive and negative — published. They also argue

that there's " a need for a new venue " to record outcomes of

well-executed but ultimately negative clinical trials. This database

must be searchable via PubMed and other search engines. Currently,

these editors note, The Oncologist is considering whether it should

become a repository for such cancer data.

 

Bottom line: It should become increasingly harder for drug companies

and others to bury embarrassing findings. But the impacts of coming

changes might not show up for five years or more. In the mean time,

let's hope our research-funding agencies, our hospitals and our

doctors don't assume that when it comes to trial data, no news is good

news.