Thursday, October 13, 2016

Considering Publishing Ethics as Research Ethics: On Recent NCATS Clinical Studies

Five years ago, Director of the National Institutes of Health (NIH) Francis Collins, was met with much criticism (mostly from big pharma execs) when he proposed a publically-funded translational medicine institute at the NIH. The National Center for Advancing Translational Sciences (NCATS) has since been up and running at the NIH, and has been under a scrutinizing eye of many in the translational research community.

A slide produced by Vtesse about VTS-270
In its short history, NCATS has had some promising breakthroughs: finding more than 50 chemical compounds that block the Ebola virus from entering cells, for instance. However, much money has been spent on VTS-270, a mixture of 2-hydroxypropyl-B-cyclodextrins, which has been shown to be a potential treatment for the deadly childhood disease Niemann-Pick Type C-1. The process in developing the compound has been sped up thanks to collaboration between NCATS and a Maryland-based company called Vtesse.

Vtesse has recently been running late-stage clinical trials of the drug by injecting the large sugars into the spinal fluid of the lumbar of patients with the disease. Prior to the lumbar puncture, the team also tried to use implanted reservoirs similar to those used to inject chemotherapeutic agents in the brain, in the brain’s ventricles. However, reservoirs in two of the three children in the study became infected.

A diagram of the reservoir system used to inject drugs into patients' brains
The mother of the twin children who had infected reservoirs is now angry that the recently published article in Current Topics in Medicinal Chemistry had no mention of the failed direct-brain administration of the compound. Although the initial research article was submitted only 9 days after the conclusion of the clinical trial in April 2013, the study was not published until 2014, almost a year later. Chris Hempel (mother of the children), brought this information to the attention of the journal’s editor. A correction has since been published, illustrating the shift from direct brain injection to the lumbar puncture technique. The clinical trial was put on hold soon after.

The case of NCATS and translational medicine brings up an interesting perspective on intent versus perception in research, as well as the ethics of research and how they parallel publication ethics. When asked about the correction, Chris Austin, the director of NCATS said, “The theme of the particular issue of the journal in which the article was published was collaborative science, and therefore the article was focused on the process and collaborative environment contributing to the development of the drug. The information regarding the clinical trial is currently being written for submission to a research journal.” It shows that this particular group of scientists believe there is a clear correlation between intent, theme, and release of certain information. However, this correlation seems to have caught the scientists in a conundrum.

One can only assume that because the scientists felt that they were publishing an article with a specific theme, they believed it was OK to omit certain information. However, the scientists completely ignore the fact that they fall under the NIH’s Ethical Guidelines for Clinical Research – specifically respect for enrolled participants by informing them of “new information…that might change the assessment of the risks and benefits of participating.” In addition, by not immediately releasing the results of the infected reservoirs to the public, they put potential participants at risk. What if another company has a similar idea and further patients become infected because they hadn’t heard of previous studies? Making both other researchers and participants ignorant of infection risk is not justifiable for thematic harmony of one article submission.

In addition, it appears that the authors specifically violated certain publishing ethics set out by both European and American societies on publishing and the scientific community, as well. In publishing, there is a documented “Seven Sins” of ethical breaches in publishing: carelessness, redundant publishing, unfair authorship, undeclared conflict of interest, human/animal subjects violation, plagiarism, and other fraud. And it’s that tricky last category, other fraud, that gets these authors. “Cooking” is defined as the selective reporting of one’s data. Let’s take a step back and think about this problem as a philosophical – even economical – one. Certain taxpayers made the grants and funding possible for this research to be done; under a tacit social contract and the not-so-tacit oath of the scientists, they agree to serve the public and not involve themselves in “evasion.” Sure, it seems nit-picky, but responsibility, integrity, and honor play an important part in institutional trust and, macroscopically, public trust of science.

No comments:

Post a Comment