This week’s selection is a brief paper with long implications. For all of us clinicians who turn to the peer-reviewed literature (either directly or through the filter of Reading of The Week) for guidance on how to help our patients, this paper is worth a read.
It is impossible to stay current on the treatment research results that emerge daily, and we look to those randomized controlled trials published in high-impact peer-reviewed journals for evidence of what works for people with the diagnoses that we find ourselves addressing in the office, the clinic, the ER or the inpatient unit. But who are those patients who sign consent forms to take part in these studies, and how much do they resemble the people sitting across from us?
Great clipboard but relevant to clinical work?
– David Goldbloom, OC, MD, FRCP(C)
Research and Practice
“What can treatment research offer general practice?”
Keith Humphreys and Leanne M. Williams
The Lancet Psychiatry, 14 December 2017 (Online First)
Over 20 years ago, the psychiatrist Egon Haberfellner attempted to recruit patients for a planned clinical trial of antidepressant medication from his community practice. He discovered that only one of the 216 patients with depression that he treated over a 6-month period in his clinic was eligible to participate. As a diplomatic understatement, he concluded that “study results obtained under restrictive inclusion and exclusion criteria are probably only applicable to a proportion of patients treated under routine conditions”. We wish to reflect more broadly on this point and encourage our colleagues to do likewise.
Most researchers of mental-health treatments—including us—aspire to produce findings that can be translated into improving the care of patients in the real world. However, scientific knowledge about treatment effectiveness is based mainly on the small and unrepresentative portion of the patient population who meet enrollment criteria for clinical research. This predicament raises the uncomfortable question of whether clinical researchers actually have as much useful information that can be translated into practice as they think they do.
To briefly summarise the conclusions of many reviews of patient selection for clinical research, mental-health treatment research, like research into many other disorders across medicine, is a gated community.
So begins this week’s Reading.
Keith Humphreys is a psychologist and the Esther Ting Memorial Professor in the Department of Psychiatry at Stanford who also served as a drug policy advisor in the Obama administration. He is a researcher, well-funded and amply published, who also takes the time to translate his work into popular media articles. His co-author, Leanne Williams, runs a laboratory for precision psychiatry and translational neuroscience as a Professor at Stanford as well. She also includes knowledge translation for the general public in her activities.
Their essay is a sober reminder that the majority of the clinical trials that inform our therapeutics – whether on their own or increasingly as ingredients in a meta-analytic mélange – are based on patient populations they evocatively describe as a “gated community”. This is not a new finding; as they begin their commentary, they note a study from more than two decades ago.
Mark Zimmerman has been making this point for years in his studies of consecutive outpatients seen at a teaching hospital in Rhode Island. For more than a decade, his research group has been studying the generalizability of trials of antidepressants and noting that most depressed patients seen in their hospital clinics would meet exclusion criteria for participation in those trials. And he has thrown down the gauntlet to the pharmaceutical industry and the Food and Drug Administration in the United States about how things need to change. (See, for example, a commentary he wrote here: http://www.psychiatrist.com/JCP/article/Pages/2016/v77n12/v77n1214.aspx.)
Indeed, the on-line appendix that accompanies the Humphreys’ commentary provides rates of exclusion of potential participants from clinical trials by psychiatric diagnosis under study, and the rates range from 30-96%. They point out that excluded participants also tend to have more psychosocial adversities to contend with. Despite the growth of effectiveness clinical trials in addition to the more traditional and pristine efficacy trials, the commentary encourages researchers to be “optimistic and proud in some respects, but could stand to be more humble in others, and sympathetic towards clinicians who have reservations about the translatability of research findings”.
And yet – the reality is that we need those “pure” randomized controlled trials of interventions as a prelude to real-world evaluation. But the lure of the new intervention may be more compelling for some researchers than evaluating the utility of one that is already in circulation. And, as clinicians, we can neither sit on our thumbs therapeutically nor rely on our last random patient experience with an intervention to dictate our next moves. The issue is by no means unique to psychiatry; one of the references in the commentary covers trials in oncology and cardiology as well. Indeed, it should encourage clinicians to fuse their art with the available science.
As an exercise, I encourage you to find a recently published randomized controlled trial of a medication or psychotherapy intervention and keep a copy simply of the exclusion criteria. And then for each patient you see in a week, see whether he or she would be accepted as a participant for the treatment you are about to prescribe. The goal is not therapeutic nihilism but rather an appreciation of the limits to the gold-standard data that guides our everyday clinical decisions. I often wondered, when I worked in our Acute Care Unit treating severely manic patients, whether they would have satisfied the inclusion/exclusion criteria of trials that inform mania clinical practice guidelines – let alone agreed to participate!
Recent sage counsel from our Australian colleagues relates to today’s Reading of the Week: this commentary highlights the gap between the world of randomized controlled trials and the role of clinical practice guidelines in informing our daily work. It’s not just about exclusion criteria when considering the translation of research into clinical care. You can find their paper here: http://dx.doi.org/10.1136/eb-2017-102701.
Reading of the Week. Every week we pick articles and papers from the world of Psychiatry.