Study criticizes journals for leaving out trial details

ABSTRACT: Published trial results fail to offer information that oncologists need for clinical translation.

JOSEPH S. BAILES, MD
Editor

Randomized controlled trials published in major oncology journals do not consistently report essential therapeutic details necessary for translation to clinical practice, according to a new study by Florida researchers. Based on their findings, the authors are calling for improved reporting from all therapy-based trials to include specific details about performing adjustments for hematologic and organ-specific toxicity.

"We're just taking it to the next logical step, which is, 'how do we apply these results to the masses of patients who need to benefit from scientific progress?" - THOMAS GEORGE, JR., MD

"We were frustrated that we were trying to adjust the therapeutics to the side effects that were occurring in the care of patients and we realized everyone had different styles," said lead author Thomas George, Jr., MD, director of the University of Florida's gastrointestinal oncology program. "For example, a clinician might reduce the dose of chemotherapy if neutropenia was detected, or add growth factors or do some combination thereof-or do nothing. So we would go to the article that established the original regimen to get an answer. We found there was so much variability among providers we could not consistently find the answers."

He said randomized clinical trials improve clinical care via evidence-based results. He noted that guidelines exist for reporting results from randomized clinical trials, but often lack specific details needed for clinical translation. Dr. George and his colleagues identified 10 essential elements of randomized clinical trial reporting, including drug name, dose, route, cycle length, maximum number of cycles, premedication growth factor support, patient monitoring parameters, and dosing adjustments for various toxicities.

The investigators analyzed all therapy-based oncology randomized clinical trials published between 2005 and 2008 in five journals (see Table).

They found that premedication, growth factor support and dose adjustments for toxicities were reported in less than half of the articles and only 30 articles (11%) met the main objective of complete data reporting (all 10 essential elements).

The highest percentages of complete data reporting were found in JNCI (25% of the time; 5/20 articles), followed by Cancer (18%; 5/27 articles), JCO (11%, 18/165 articles), Blood (5%; 1/19 articles); and NEJM (3%; 1/31 articles).

TABLE Publications analyzed 165 articles in

Journal of Clinical Oncology (JCO)

31 articles in

New England Journal of Medicine (NEJM)

27 articles in

Journal of the National Cancer Institute (JNCI)

19 articles in

Blood

20 articles in

Cancer

Total: 262 articles

"It just boils down to willpower on the part of the journal editors to agree that this is an important issue," Dr. George said. "I think the scientific community, the publishers, the editors, and even the investigators who conduct the studies have been appropriately focused on justifying the scientific methods and merit of the study. We're just taking it to the next logical step, which is, 'how do we apply these results to the masses of patients who need to benefit from scientific progress?'"

The researchers found that the dose of the drug was almost always reported. However, only 43% of the papers reported what kind of premedication was necessary and only 42% reported how they adjusted dosages if the therapy proved toxic (J Natl Cancer Inst 102:702-705, 2010).

"This study is a pretty good wake-up call. So now it is out there for consumption. I think it is capable of being done on its own and there is no need for a special study group on this," Dr. George told Oncology News International. "The journal editors need to acknowledge this is a problem, and they need to require the authors of studies to submit these 10 essential elements just as they include elements that verify the scientific merit of the trial."

The journal editors could include the original protocol of the studies in their online appendix, he suggested, and then it wouldn't require any more than a click of a mouse to access.

"If this were done," he said, "clinicians would have access to all the details needed to safely prescribe [for] and monitor patients, and they would know what to do when toxicity occurs."

John Richart, MD, an associate professor in the hematology and medical oncology division at Saint Louis University School of Medicine in St. Louis, said he agreed with Dr. George and added these changes could be accomplished with very little added time or cost. Oncologists and their patients could greatly benefit if these 10 essential elements were available online, Dr. Richard said.

"This is an issue that is important and it could be easily addressed," he said. "I have been in the situation where I have been treating a patient and gone back to the protocol and reviewed the treatment plan. If it is a clinical trial that I don't have access to, then it can be a problem. If you are trying to follow a trial, it would be nice to have access to the trial design and treatment plan, and that is not the case now."

William Blackstock, Jr., MD, said many oncology patients suffer serious and preventable toxicities that could be avoided if Dr. George's proposal were adopted by most major medical journals. Dr. Blackstock is a professor and chair of radiation oncology at Wake Forest University Baptist Medical Center in Winston-Salem, N.C.

"The authors bring needed light to an element of reporting clinical trial results that has been neglected. It is not uncommon that the [findings] of studies that result in practice changes prove difficult to implement in the community because there is a lack of detail around how to deliver a specific chemotherapy regimen or radiation technique, resulting in potentially preventable toxicities for patients," Dr. Blackstock said.

VANTAGE POINT

ALEX ADJEI, MD, PHD Information is accessible through other means

The information from clinical trials that is important for clinical translation is already available from other sources, said Dr. Adjei, senior vice president of clinical research and chair of the department of medicine at Roswell Park Cancer Institute in Buffalo, N.Y. He added that Dr. George and colleagues are asking journal editors to make changes that are not entirely necessary.

"[The study] makes this a much bigger problem than it is," according to Dr. Adjei. "Every oncologist knows how to use approved drugs and a new drug that gets added to the standard of care is going to come with a package insert, so the information necessary for administration is there. It may not be in the manuscript itself, but it is [available]."

Dr. Adjei agreed that it would be more convenient for the oncologist to have all the information available in one place and added that this could be given as supplemental information online, but feels the study by Dr. George and colleagues may be overstating the case somewhat.