Despite being set up to protect vulnerable participants, these boards are ill-equipped to ensure research is safe, especially regarding post-exertional malaise (PEM).
Last year, researchers in Ontario, Canada started recruiting participants for a Long COVID trial testing the feasibility of exercise and rehabilitation. Like many other studies of exercise, it doesn’t use validated measures for post-exertional malaise (PEM). But the Pursuing Reduction in Fatigue After COVID-19 via Exercise and Rehabilitation (PREFACER) study, run by researchers at Western University, stands out because it involves deceiving participants — undermining informed consent and potentially violating Canadian ethical research standards.
The trial pits usual care, which refers to any off-label medications or supplements people are already taking, against personalized exercise and rehabilitation. But rather than informing participants they’re taking part in an interventional study, meaning that one group will receive an experimental treatment, the researchers use a “modified Zelen design” that conceals this fact.
Participants are initially told that they are taking part in an observational study designed to follow Long COVID and assess the costs of standard care, but half will receive the exercise intervention.
The researchers justify this study design by claiming that people with Long COVID have a bias against exercise, and that concealing the initial study design would mask any so-called “nocebo effects,” in which people experience side effects because they think they’re being harmed.
This design undermines informed consent principles that require full disclosure as outlined in the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. This is the mandatory policy for conducting human trials in Canada at federally-funded institutions. It does not allow for a deceptive design in studies where there is a real potential for harm. The study authors dismiss this, despite extensive evidence that exercise can harm people with Long COVID who have PEM and those with myalgic encephalomyelitis (ME).
In January, I sent a letter signed by 11 patient advocates, journalists, and researchers to the study’s ethical committee. Research ethics boards like this one meet to review study protocols submitted by researchers before they undertake a study, to ensure that it aligns with ethical standards and federal regulations.
The letter’s signatories included Todd Davenport, professor at the University of the Pacific and PEM expert who also authored his own rapid response to the study protocol. Our letter requested a formal review of these issues to ensure compliance with ethical standards, and recommended that people with Long COVID be included in study design. The researchers had also shared recruitment posters in Long COVID patient groups without linking the research ethics board study approval number, preventing prospective participants from confirming the veracity of the study.
The researchers responded to Davenport’s criticism, arguing that they’re “asking participants themselves, about the acceptability of the consent approach” as part of the study’s outcomes, as well as disclosing potential harms to those in the exercise arm. But before they’re told they’re part of an interventional study, the participants are under the assumption that exercise is part of usual care.
This response “talked around the key decision point in deciding whether deception is ethical: whether the consequences constitute no more than the risk encountered in daily life,” Davenport told me. “There is no evidence-based justification that graded exercise is a minimal risk intervention.”
Naveen Poonai, a pediatrician who serves on the Health Sciences Research Ethics Board, told The Sick Times over email that there would be a post-approval ethical review of the study in March. Despite emails on March 11 from Poonai indicating that we’d receive a response to our letter, it was never sent to us.
When I followed up on April 23, Erika Basille, the director of research ethics and compliance, wrote that the board had sent a response letter to the ME|FM Society of British Columbia, which also lodged their concerns, but inadvertently did not include us in email communications. The ethics board declined to send the response directly to us and we had to reach out to the the ME|FM Society ourselves to access it.
In its response, the post-approval ethical review concluded that the trial held minimal risk and cited several guidelines that suggest exercise may be safe and beneficial for PEM. They stated that the protocol aligns with several guidelines from various medical associations and societies — but those guidelines base their conclusions off poorly conducted, low-quality studies.
The lack of a direct response from the ethics committee reflects the low level of care and competency that plagues Long COVID studies. Research ethics boards need more education and basic training about the disease to prevent potentially harmful trials with no plausible scientific basis from receiving approval.
There is no evidence-based justification that graded exercise is a minimal risk intervention.
Todd Davenport, University of the Pacific
Unethical research endangers participants
The annals of clinical research are filled with stories of unethical conduct. The Tuskegee syphilis study, in which Black men were denied treatment for decades, is one of the most infamous cases. In another less famous but equally horrifying experiment, in 1963 at the Jewish Chronic Disease Hospital, researchers injected live cancer cells into bedbound patients without their consent.
Unethical studies are not a relic of the past. This year, the Centers for Disease Control and Prevention (CDC) tried to fund a $1.6 million Hepatitis B vaccine study in Guinea-Bisseau, which would deprive vulnerable children of proven, effective vaccines.
While they don’t garner the same media coverage, researchers worldwide are running unethical Long COVID and ME trials testing potentially harmful interventions like exercise, cognitive behavioral therapy (CBT), and a handful of poorly-evidenced “neuroplasticity” programs. Another Canadian study testing swimming as a treatment for ME was suspended earlier this year, to investigate a complaint from someone within the community concerned about the trial’s potential harms. Since PEM is seldom measured or even mentioned in these studies, that harm may go unreported.
In all these cases, a research ethics board approved these protocols while overlooking or failing to spot the risks. This ignorance and neglect reflect a fundamental knowledge gap among researchers as well as the committees that review and greenlight these trials.
“Research ethics boards ensure that there’s an adequate balance of benefits and risks to participating in a research study,” said Davenport, who has served on research ethics boards. “Some ethics boards consider it in their purview to ensure that there is high quality, generalizable knowledge that will come out of a study.”
“It takes a lot of background knowledge to be able to adequately review a study protocol,” Davenport said. But much of the information that reviewers evaluate is self-reported by investigators. He added that reviewers sometimes defer to the information that investigators provide without fully checking their claims.
This ignorance and neglect reflect a fundamental knowledge gap among researchers as well as the committees that review and greenlight these trials.
Long COVID has seen an increase in research interest, and uninformed scientists have run dozens of low-quality trials under the unproven premise that these conditions are driven primarily by deconditioning and psychological factors. In doing so, researchers are borrowing flawed concepts from discredited ME trials that ultimately harmed patients.
The infamous 2011 PACE trial in the U.K. trafficked the false idea that CBT and graded-exercise therapy were an effective treatment for ME. During the trial, the researchers changed their outcomes to inflate the treatments’ benefits, failed to collect any objective measures, had high dropout rates indicating many participants had poor experiences, and refused to release the data to other researchers to verify their analysis. The results were still influential enough to pollute medical guidelines, though now these treatments are no longer officially recommended by the U.K.’s National Institute for Health and Care Excellence and the CDC.
The PREFACER study at Western University follows this legacy of poor-quality research. Davenport had a lot of questions about how the study would reduce the harms from the exercise intervention and how well the researchers relayed the risk to participants.
Deception in this context is also concerning since people with Long COVID already face substantial stigma when accessing healthcare.
Like many other researchers jumping to study this disease, the authors of the PREFACER study use invalid measures of PEM. It uses the DePaul Symptom Questionnaire to assess PEM severity and frequency, which is not intended to measure this symptom but rather screen for people who may have it.
The researchers aren’t using more appropriate measures, like the FUNCAP questionnaire, and they don’t factor in that PEM occurs often after a 24-hour delay and will not show up immediately after physical exertion. They also claim to “monitor PEM” using wearable devices, which are not validated for PEM.
“I’m not convinced that they’re excluding anyone who has PEM,” said Davenport. Based on the way they’re measuring it, it isn’t clear that they understand it either.
People who are able to should write letters of concern and complaints to institutional ethics boards when studies like this one are greenlit.
But the onus shouldn’t be on people with Long COVID and ME to call out potentially unethical research practices. Researchers must review recent work that details how Long COVID studies should be conducted to measure health outcomes without harm.
Herein lies the paradox. Institutional ethics committees might not know better, but advocates and researchers with lived experience have energy limitations and often aren’t able to mobilize quickly when unethical trials are proposed. Per Brandolini’s Law, the energy it takes to refute misinformation is an order of magnitude greater than the energy required to create it.
Research ethics boards need training to understand the basics of medically neglected diseases so that potentially harmful studies based on outdated or unsupported hypotheses do not move forward. When these studies proliferate and poison the medical literature, they become fodder for rehabilitation clinics and self-help gurus to sell unevidenced treatment plans. These multiply the harms for an already medically neglected group of people.
When these studies proliferate and poison the medical literature, they become fodder for rehabilitation clinics and self-help gurus to sell unevidenced treatment plans. These multiply the harms for an already medically neglected group of people.
Simon Spichak is a Toronto-based science and health writer with a MSc in neuroscience. His work has been published in Being Patient, National Geographic, MIT Tech Review, The Guardian’s Scientific Observer, The New York Times, and other outlets. He was a recipient of the 2025 National Press Foundation’s Rare Disease Reporting Fellowship. He is the founder of a low-cost online therapy clinic called Resolvve and runs a newsletter about underreported health and disability issues in Canada.
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