From the Editor
Years ago, I worked with a patient who lost 70 pounds with an aggressive regiment of exercise. His determination was exceptional but his struggles with obesity weren’t. People with schizophrenia are twice as likely as the general population to deal with weight problems.
In the first selection, we consider a paper on weight loss for those with schizophrenia and related illnesses. STEPWISE offered these patients a thoughtful approach to weight management. The paper is remarkable for its finding: the intervention didn’t work. As the University of Southampton’s Dr. Richard I. G. Holt and his co-authors write: “the intervention was neither clinically nor cost-effective over the 12-month intervention period.”
In this Reading, we consider the paper, but also the larger issue of negative trials and their lack of presence in the literature.
In the second selection, we draw on a New York Times essay by pediatrician Aaron E. Carroll who calls for the publication of more negative trials. “These actions might make for more boring news and more tempered enthusiasm. But they might also lead to more accurate science.”
Weight and Weight Management
“Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis (STEPWISE): randomised controlled trial”
Richard I. G. Holt, Rebecca Gossage-Worrall, Daniel Hind, Michael J. Bradburn, Paul McCrone, Tiyi Morris, Charlotte Edwardson, Katharine Barnard, Marian E. Carey, Melanie J. Davies, Chris M. Dickens, Yvonne Doherty, Angela Etherington, Paul French, Fiona Gaughran, Kathryn E. Greenwood, Sridevi Kalidindi, Kamlesh Khunti, Richard Laugharne, John Pendlebury, Shanaya Rathod, David Saxon, David Shiers, Najma Siddiqi, Elizabeth A. Swaby, Glenn Waller and Stephen Wright on behalf of the STEPWISE Research Group
The British Journal of Psychiatry, 25 September 2018 FirstView Open Access
People with schizophrenia die 10–20 years earlier than the general population, with approximately 75% of deaths resulting from physical illness. The twofold increased prevalence of overweight and obesity contributes to this excess mortality. Some, but not all, studies suggest that dietary and physical activity interventions may reduce weight gain.
Many weight loss programmes involve one-to-one strategies to promote behaviour change but these are unlikely to be affordable in many healthcare settings. Group-based structured education offers an alternative approach, and has been adopted by the UK National Health Service (NHS) Diabetes Prevention Programme. The National Institute for Health and Care Excellence (NICE) recommends that lifestyle interventions should be offered to people taking antipsychotics but there is insufficient evidence to inform how these should be commissioned.
We designed the STEPWISE group-based lifestyle structured education and then conducted a randomised controlled trial (RCT) to evaluate whether STEPWISE could lead to clinically relevant weight loss after a year in adults with schizophrenia, schizoaffective disorder or first-episode psychosis. Further objectives were to assess the impact on physical activity, diet, biomedical measures and quality of life, intervention fidelity, acceptability to participants and mental health services, and cost-effectiveness.
So begins a paper by Holt et al.
Here’s what they did:
- “STEPWISE was a two-arm, parallel group RCT comparing the STEPWISE intervention with treatment as usual (TAU)…”
- Participants were recruited through clinics and with posters and leaflets, and needed to be 18 or older, and to have a diagnosis of schizophrenia, schizoaffective disorder, or first-episode psychosis.
- Participants needed to be over 25 in their BMI, or to have expressed concern about their weight.
- The STEPWISE intervention took place over 12 months, and involved both group work and individual sessions, and included: “(a) behaviour change theory specifically with a focus on food and physical activity; (b) psychological processes underlying weight management; (c) challenges of living with psychosis and its impact on eating and weight.” See figure below.
- The control group received printed advice on lifestyle and the risks associated with weight gain.
- The primary end-point was weight change at 12 months.
- The authors also did a cost-effectiveness analysis which considered health and social care costs, and also societal costs (“calculated using police costs, productivity losses from lost education and employment and informal care costs”).
- Statistical analyses were done.
Here’s what they found:
- Between 10 March 2015 and 31 March 2016, they screened 1253 patients of whom 414 enrolled.
- “412 participants (207 intervention, 205 control) were included in the final intention-to-treat analysis. In total, 168 (81.2%) intervention and 173 (84.4%) control participants completed the study…”
- Demographically: most participants had schizophrenia, had been on antipsychotics for 10 or more years, and were ethnically white. The gender mix differed between the intervention and control groups (55.6% male in the intervention group vs. 46.3% control). The intervention group was 3 kg heavier on average than the control group (in part because of the gender mix).
- “The primary comparison of weight change at 12 months was almost identical between arms, with a mean reduction in weight of 0.47 kg in the intervention group and 0.51 kg in the control group… There was no difference in percentage weight loss or percentage of participants maintaining or losing weight.”
- “Both groups had similarly low physical activity levels at baseline. After 3 months, weekend moderate-to-vigorous physical activity was significantly higher in the intervention group, but this difference had disappeared by 12 months.”
- “The intervention produced 0.0035 more QALYs. The mean total health and social care costs were £5255 for STEPWISE participants and £4453 for control participants. The mean total societal costs were £11 332 for STEPWISE participants and £10 305 for control participants.”
The STEPWISE trial successfully recruited and retained participants; however, the intervention was neither clinically nor cost-effective over the 12-month intervention period. Both groups lost ~0.5 kg but weight change did not differ between groups. There was no sustained behaviour change in diet and physical activity needed to promote weight loss.
- This is a good study.
- The results are a bust. As the authors note: “The challenge of managing obesity and weight gain in people with schizophrenia remains and other approaches are needed.”
- The authors do note that many other studies in this area have failed to show results. Indeed, in a recent meta-analysis of six studies, just two showed positive results – a comment on how challenging weight problems are in this population. The authors speculate that a more intensive intervention may be needed. Of course, we can ask if the way to manage weight is to take a more preventive approach, incorporating education when medications are initiated.
- The negative result is interesting. Quick check: it’s the only negative result in that journal that month.
- Why aren’t there more negative studies? Our next selection offers some insights.
Studies and Results
“Congratulations. Your Study Went Nowhere.”
Aaron E. Carroll
The New York Times, 24 September 2018
When we think of biases in research, the one that most often makes the news is a researcher’s financial conflict of interest. But another bias, one possibly even more pernicious, is how research is published and used in supporting future work.
A recent study in Psychological Medicine examined how four of these types of biases came into play in research on antidepressants. The authors created a data set containing 105 studies of antidepressants that were registered with the Food and Drug Administration. Drug companies are required to register trials before they are done, so the researchers knew they had more complete information than what might appear in the medical literature.
Aaron E. Carroll
So begins an essay by Dr. Carroll.
Drawing on the Psychological Medicine paper, he notes four types of bias:
Publication bias. Publication favours positive results: “With the 105 studies on antidepressants, half were considered ‘positive’ by the F.D.A., and half were considered “negative.” Ninety-eight percent of the positive trials were published; only 48 percent of the negative ones were.”
Outcomes reporting bias. The result write-ups tend to favour positive results while not reporting the negative. “In 10 of the 25 negative studies, studies that were considered negative by the F.D.A. were reported as positive by the researchers, by switching a secondary outcome with a primary one, and reporting it as if it were the original intent of the researchers, or just by not reporting negative results.”
Spin. Abstracts tend to make the results look better than they are. “Of the 15 remaining ‘negative’ articles, 11 used spin to puff up the results.”
Citation bias. Papers tend to cite positive findings. “Positive studies were cited three times more than negative studies.”
He notes the impact: though only half the research was positive, “nearly all the studies were positive.”
This problem is worldwide. In 2004 in JAMA, a study reviewed more than 100 trials approved by a scientific-ethical committee in Denmark that resulted in 122 publications and more than 3,700 outcomes. But a great deal went unreported: about half of the outcomes on whether the drugs worked, and about two-thirds of the outcomes on whether the drugs caused harm. Positive outcomes were more likely to be reported. More than 60 percent of trials had at least one primary outcome changed or dropped.
He notes steps that can address these biases:
We can demand that trial results be published, regardless of findings. To that end, we can encourage journals to publish negative results as doggedly as positive ones. We can ensure that preregistered protocols and outcomes are the ones that are finally reported in the literature. We can hold authors to more rigorous standards when they publish, so that results are accurately and transparently reported. We can celebrate and elevate negative results, in both our arguments and reporting, as we do positive ones.
- This is an important essay.
- The author makes good observations – and good suggestions.
- That said, I have noticed negative studies have appeared more in the literature (I’m drawing from my own reading, rather than any study.) For example, this Reading opens with a big paper with a not-so-big result. In last month’s American Journal of Psychiatry, the Kennard et al. study on an app-based intervention to reduce suicidal behaviours in adolescents was remarkable for being unremarkable. “The ASAP intervention did not have a statistically significant effect on suicide attempt…” The paper can be found here: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.17101151.
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.