Trial By Error: UK Funds Genetics Project; My Letter to CODES Investigators

By David Tuller, DrPH

UK Funding for Major Genetics ME Study

Two of the UK’s largest public funding agencies announced this week that they would provide £3.2 million (around $4 million at current rates) for a study that will analyze genetic material from as many as 20,000 people to search for underlying causes of myalgic encephalomyelitis. The Medical Research Council and the National Institute for Health Research are providing, respectively, £1.8 million and £1.4 million to support the project, called DecodeME.

While this sum represents a significant investment, it is still much less than the £5 million that the MRC and other government agencies spent on the now-discredited PACE trial more than a decade ago. Contrary to the expectations, and claims, of the PACE investigators, that piece of crap documented pretty authoritatively that cognitive behavior therapy and graded exercise therapy are not effective treatments for ME (or chronic fatigue syndrome, the term they favored.)

The new study is what is called a genome-wide association study, or GWAS. Here’s how lead investigator Chris Ponting, a professor of genetics at the University of Edinburgh, described the approach in a press release from the research team:

“Our focus will be on DNA differences that increase a person’s risk of becoming ill with ME/CFS. We chose to study DNA because significant differences between people with, and without, ME/CFS must reflect a biological cause of the illness. It is our hope that this study, the world’s largest genetic analysis so far, will transform ME/CFS research by injecting much-needed robust evidence into the field.”

The project was developed, with significant patient input, by the UK CFS/ME Research Collaborative, which was established in 2013, and the CureME Biobank at the London School of Hygiene and Tropical Medicine. Professor Ponting became vice-chair of CMRC in 2018 after the previous vice-chair stepped down. Professor Ponting’s predecessor, the methodologically and ethically challenged Professor Esther Crawley of Bristol University, failed in her efforts to land two major grants–one from MRC and another from the Wellcome Trust. Her focus on psychological and behavioral interventions like cognitive behavior therapy and the Lightning Process also angered patients.

Andy Devereux-Cooke, a patient who has been involved in setting up the study, said this in a statement: “As someone living with ME/CFS, I’m well aware that the patient community has waited a long time for a study such as this one that has such a strong, genuine element of patient involvement. All of us involved with this research project hope that it can start to address the totally unwarranted stigma and lack of understanding that so many patients with ME/CFS face on a daily basis.”

The study is not scheduled to begin for some months, but anyone with ME/CFS who is 16 or older and might like to participate can register their interest in advance. The study will use both the 2003 Canadian Consensus Criteria for ME/CFS and the 2015 Institute of Medicine definition for what it called–unfortunately–systemic exertion intolerance disease, or SEID. *(Both of these were created as clinical case definitions, not research case definitions.) [This sentence has been corrected. See below.]

Some patients have criticized the GWAS study for not using another definition, the 2011 International Consensus Criteria for ME. Others still mistrust the CMRC after Professor Crawley’s rocky tenure. Under her leadership, the organization pursued a project called the ME/CFS Epidemiology and Genomics Alliance (MEGA), which bears superficial resemblance to DecodeME. At the time, patients feared that Professor Crawley would use the MEGA data to pursue her sub-par research into psychological and behavioral aspects rather than to seriously investigate pathophysiological processes.

That’s why I wasn’t surprised at the lively discussion among commenters when I wrote about this project in January. The patient advocacy group Opposing MEGA remains skeptical of the new study. In response to my previous post, a commenter on Opposing MEGA’s Facebook page wrote: “No way would I trust my data with this research group. This is a rerun of the MEGA proposal with revisions to overcome the failure first time round.”

I have more optimism about this project than that. But given the history of how people with this illness have been treated, I understand why others might have concerns.

*The sentence previously read: (The latter was meant to be a clinical case definition and not a research case definition, but the combination of the two sets of criteria has become fairly common among investigators.) It was not accurate to write that this combination is “fairly common.” As always, I apologize for the error.


My Letter to the Investigators of the CODES Trial

Subject: Invitation to respond to my posts about CODES

Dear Professors Goldstein, Stone and Chalder–

I have recently posted some blogs about the CODES trial on Virology Blog, a well-read science site hosted by Professor Vincent Racaniello, a microbiologist at Columbia University. These posts are herehere and here

Given my critical assessment, I felt it was important to offer you a chance to respond directly to the concerns I have raised. If you send me your comments, at whatever length you choose, I will be happy to post them in full on Virology Blog, without editorial comment or interruption. If I decide to respond, I will do so in a separate post. (I have cc’d Professor Racaniello on this e-mail.)

Earlier this month, I also wrote to King’s College London to express concerns about the problematic press release for CODES. The press release failed to mention that the primary outcome had null results and that any reported benefits were from secondary outcomes. It is perplexing that KCL would omit such key details when communicating important scientific findings to the public.

Since I have not yet heard back from KCL, perhaps you could address this issue as well in your comments. Did you all read and approve the press release before it was disseminated? Do you stand by KCL’s decision to not distinguish between the results for the primary and secondary outcomes?

Thanks much. I hope to hear back and have the opportunity to post your full response on Virology Blog. Please consider this a standing invitation.


David Tuller, DrPH
Senior Fellow in Public Health and Journalism
Center for Global Public Health
School of Public Health
University of California, Berkeley

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