SPIRIT and SEPTRE: Research Protocols You Can Build

Dr Amy Price

Evidence Building Protocols

When developing a protocol for a clinical trial there are clear steps to building good methods, truth, accuracy and transparency into the research.  The SPIRIT statement says it best:

“The protocol of a clinical trial is essential for study conduct, review, reporting, and interpretation. SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) is an international initiative that aims to improve the quality of clinical trial protocols by defining an evidence-based set of items to address in a protocol”.

SPIRIT is a great free tool. But soon there will be an online trial protocol builder (presently in testing) called SEPTRE, which will help every protocol step, with mouse overs and videos for added information and ways to proceed.

The SEPTRE initiative is chaired by Dr. An-Wen Chan, a firm believer in medical research transparency.  

Research results that fail to support the hypothesis are seldom published, which can be dangerous for healthcare. Without being able to view negative and positive research together, doctors can only make prescribing decisions based on what they see: a set of studies that are inherently biased toward positive results.

“When that happens”, Chan says “it’s the patients who potentially suffer, particularly those who are exposed to ineffective or costly treatments, or even worse, harmful ones.”

Research Transparency Saves Lives and Families

I know this first hand after witnessing the effects of prescription of hypnotic sleep drugs to a family member who after taking the medication, he and his doctor trusted would help, committed suicide. Years later the psychiatrist and family would learn that psychosis, suicide, and self-harm were unreported side effects that showed up even during animal testing and were present during all phases of clinical trials testing, but the adverse events were left unreported.

Finding unpublished research is a learned skill. I have scoured thousands of conference abstract without finding a usable unpublished trial. The time I got closest was during my first ever medical conference where one of the presenters had a near nervous breakdown during his presentation, screaming that the sponsor threatened to sue him if he published the “real” results of his research and that he had blood on his hands. Needless to say that was not in the conference abstract and it was never published.

Is Knowing Better Enough?

While it was widely discussed that he – the presenter – should have known better, his career was over. Were the others too smart and moral to be trapped like that? There was a gnawing awareness that gripped me and was indelibly printed on my heart. All of us could be vulnerable when funding is elusive and a sponsor offers the dream with a golden handshake and just a small “concession”. We can cite platitudes like “All that glitters is not gold” and “What we compromise to keep will destroy our foundation” but the greatest protection for medicine and for us is a culture of transparency, where good reporting becomes a habit without exceptions.

Finding Unpublished Trials

In case you wonder how to find unpublished trials, Chan’s BMJ article, Out of sight but not out of mind: how to search for unpublished clinical trial evidence, is open access. Chan discusses how to retrieve unpublished data that researchers otherwise would miss.

Another great resource for materials submitted to the FDA is the Clear Road Map.This is a commercial solution but there is a lot of freely accessible information on the site. Systematic literature reviews with published and unbalanced research can offer a balanced view of how a drug performs overall across multiple studies, compared to the small snapshots provided by individual studies. This is elegantly demonstrated in the Tami-Flu  campaign. This changed the life and research of one investigator, Dr Tom Jefferson, who is speaking at Evidence Live and who is leading one of the free to attendees fringe events “Evidence in the pub/college bar – Diary of a Tamiflu Research Parasite” Thursday June 23rd 18:15 – the Terrace Bar, Somerville College, plus meet Dr Chan at Evidence Live 2016.  An-Wen Chan – Leap of faith or formula for success: Championing careers in evidence-based medicine

Last Thoughts to Consider

“But reviews that only consider published data still don’t give doctors a good picture, because they’re missing so much of the whole story,” says Chan. “When research is not reported transparently it’s not only less helpful, but also potentially dangerous. It goes against why we do research – which is to learn the truth for the benefit of patients.”