AAfter living in Oklahoma for 40 years, Nita and Doug Thatcher retired in 2009 to the Rust Belt city of Lorain, Ohio, a Cleveland suburb that hugs Lake Erie. When Nita needed to find a new primary care doctor, a friend recommended someone from the Cleveland Clinic. Nita knew the institution’s reputation for cutting-edge research and superior medical services. But as a longtime patient grappling with chronic fatigue syndrome, a debilitating disorder that scientists still don’t fully understand, she was wary when she learned that the clinic was promoting a common but potentially dangerous treatment for the illness: a steady increase in activity known as graded exercise therapy.
The notion that people with chronic fatigue syndrome should be able to exercise their way back to health has enjoyed longstanding and widespread support, and “graded exercise” has become the de facto standard of clinical care. This approach has obvious intuitive appeal. Exercise helps all kinds of illnesses, and it’s a great tool for boosting energy. How could it possibly hurt?
British psychiatrists and psychologists developed the graded exercise strategy for treating chronic fatigue syndrome during the 1990s. They offered a straightforward rationale: These patients were not medically sick but severely out of shape (“deconditioned”) from prolonged avoidance of activity. And they avoided activity because they wrongly believed they had a biological disease that would get worse if they overexerted themselves. During treatment, patients were encouraged to question this “dysfunctional cognition,” view any resurgent symptoms as transient, and push through the exhaustion and pain to rebuild their strength.
Today, leading research supporting graded exercise therapy, often called GET, is unraveling, and the scientists behind that research, along with the esteemed journals that published their findings, have come under fire for what have been called dubious study methods and a questionable peer review process. Meanwhile, millions of patients like Nita who are afflicted with chronic fatigue syndrome — a disorder I have covered for nearly a decade as a health reporter, and about which I have sometimes been as much a crusader as a journalist — continue to combat the therapy’s implied prejudices: that sufferers are out of shape but not medically sick, and that increasing exercise levels will help.
Decades after the enigmatic ailment was first identified, the precise causes of chronic fatigue syndrome remain a mystery, but what is clear is that neither of those assumptions is true. It is very likely, in fact, that the advent of graded exercise therapy, ostensibly designed to free chronic fatigue syndrome sufferers from an array of debilitating physical and cognitive symptoms, instead made them worse — sometimes much worse. And while the hard questions now being raised about this treatment approach would seem a welcome outcome for public health, it’s cold comfort for those patients who have been subjected to it without any sound science to back it up — yet one more insult for those with a disorder that seems to court misunderstanding.
Nita is among them. She had already tried graded exercise therapy before her arrival in Ohio, and it had not gone well. In 1997, after she had been ill for many years, her doctors in Oklahoma prescribed an exercise regimen that left her much more disabled than before. For a couple of years afterward, she could barely leave the house, and she never returned to her pre-GET level of function. Other patients have routinely reported a similar experience: an extended relapse after they pushed themselves beyond their limits, a symptom often called “post-exertional malaise.” In surveys, patients who have undergone GET have been more likely to report that they got worse, not better.
Nita finally enrolled at the Cleveland Clinic outpatient center near her home, but only after grilling her prospective physician to make sure the graded exercise approach was off the table. “I heard some horror tales about the Cleveland Clinic pushing this, and the Mayo Clinic,” Nita told me over Memorial Day weekend, during an interview at her home — one in a series of conversations conducted in recent months via email, on Facebook, and in person. Later on, she added: “A doctor prescribing graded exercise therapy for this illness would be as irresponsible as a doctor prescribing gradually larger doses of sugar for a diabetic.”
At 67, Nita has coped for decades with the extensive physical and cognitive impairments that characterize chronic fatigue syndrome, from extreme and unrelenting exhaustion to difficulties with memory and concentration, among other symptoms. These days, she spends most of her time in her ground-floor bedroom, settled into a brown recliner. She can sustain a lively and engaged conversation for 15 or so minutes, then starts fumbling over words and needs to rest. She can email or chat with friends on Facebook for up to half an hour, perhaps three times a day. She likes reading light romance novels “because they have a happy ending, they’re not draining.” She doesn’t watch TV— trying to keep up with the plotlines is “too stimulating,” she says.
She and her husband Doug, a Methodist minister, live two blocks from a sandy Lake Erie beach, in a modest Craftsman house on a street lined with other modest Craftsman houses — the kind ordered from Sears in the early 20th century. Nita loves the lake. Being in nature has always felt like “coming home” to her, she says: The lake was one reason the couple returned to Ohio, where they’d both grown up. But she rarely sees the water.
To relax and “zone out,” she leans back in her recliner, closes her eyes and remembers the hikes she took in the years when she could still hike, or conjures images of the hikes she has never done.
“I’ve always been an outdoor person,” she says. “In my mind, I still go hiking, on the shore, in the woods.” Online tools help. “Sometimes I’ll take a hike on my computer. I see trails on Google Earth.”
Chronic fatigue syndrome has been controversial ever since the U.S. Centers for Disease Control and Prevention published its first major journal report on the illness, in 1988. For decades, patients have confronted enormous skepticism and doubt about whether their illness even exists. Yet a significant body of research has demonstrated that the disorder has a physiological basis and does not result from deconditioning or psychiatric problems. In August, a study in the Proceedings of the National Academy of Sciences reported finding distinctive metabolite patterns in the blood plasma of patients with chronic fatigue syndrome, suggesting that multiple metabolic pathways are out of whack.
But patients like Nita have long suffered mistreatment and abuse from the medical and research establishments. I visited her last spring, not long after we connected through the extensive online network of chronic fatigue syndrome patients. I was looking for patients whose doctors had prescribed exercise therapy. Nita had read my previous reporting about the illness and was eager to share her story, although she knew being interviewed would tax her resources.
In our communications, I felt guilty whenever I pressed for more information. I knew responding to each question — and Nita responded conscientiously and in-depth — took something out of her.
For my part, I never planned to become “the chronic fatigue syndrome reporter.” Telling news editors you cover chronic fatigue syndrome is not a helpful career move. At a dinner party, the topic is a conversation-stopper. But after a friend got diagnosed with the syndrome many years ago, I knew he was sick because he was sick, not because he was lazy, depressed, or delusional. In 2009, when research suggested that a strain of mouse virus could be implicated in the disorder, I wrote a number of articles about the ensuing scientific controversy for The New York Times. After further studies attributed the apparent mouse virus link to lab contamination and led to retraction of the initial research, public and media interest in the issue evaporated. But I couldn’t shake the story. I knew these people needed medical help. Yet no one seemed to take the illness seriously.
As a result, I’ve been in touch with a lot of chronic fatigue syndrome patients over the years. Some have much more moderate cases than Nita, some more severe. One thing I quickly learned is that many prefer a more serious-sounding name, myalgic encephalomyelitis, which means inflammation of the brain and central nervous system, along with muscle pain. The term, often shortened to M.E., was coined in the late 1950s after an outbreak of illness at a London hospital. It has been listed for decades as a neurological disorder in the World Health Organization disease classification system — although whether the term is an accurate description of the physiology of the disorder remains somewhat open to debate. These days, some government agencies and advocacy groups, in a compromise of sorts, call the disorder ME/CFS.
Last October, Virology Blog, a popular science site hosted by the Columbia microbiology professor Vincent Racaniello, published my lengthy investigation of the major flaws in a British clinical trial called PACE — the largest and, supposedly, the definitive study of treatments for chronic fatigue syndrome. The main results were published in The Lancet in 2011 and the journal Psychological Medicine in 2013. The trial was led by some of the same experts who had developed graded exercise therapy in the first place, and not surprisingly, their publicly reported findings represented an endorsement of their theories about deconditioning and “unhelpful” illness beliefs.
The PACE investigators acknowledged that ME/CFS patients might feel worse after exercise, but they attributed this to the expected effects of deconditioning, not to the exacerbation of an underlying pathology. Anyone who suffered a serious crash after a course of graded exercise, they argued, had most likely received treatment from untrained clinicians. (The investigators have always acknowledged that an acute viral infection or other sickness can trigger the syndrome. The problem, they claim, is that patients continue to insist they have a medical disease long after the initial episode of illness is over.)
Given the paucity of treatment options, medical institutions and public health agencies were promoting exercise regimens even before the 2011 publication of the Lancet paper, largely based on some smaller studies conducted by the same researchers, as well as colleagues who shared their perspective. The reported success of the PACE trial reinforced that trend — although other researchers have found that ME/CFS patients can best avoid relapses and minimize their symptoms, as Nita does, through a popular self-help approach known as “pacing.” Under this strategy, patients learn to accept their limited capacities and adjust their activities so as not to exceed their perceived energy levels, often called their “energy envelope.”
As it stands, the direct cause, or causes, of ME/CFS remain largely unknown, and there is no definitive treatment. But as I investigated the PACE trial — with its promotion of exercise and increased activity as the path to “recovery” from the disorder — I came to view it as a powerful case study of scientific wrongdoing. Thanks to the incisive analyses of some very smart patients and advocates, I gradually understood how deeply flawed it was and how much harm it was causing. I knew it needed to be publicly and authoritatively discredited.
I also knew I needed to be part of that effort.
In the U.S., it is estimated that about one million people suffer from chronic fatigue syndrome, and millions more suffer worldwide, although many cases remain undiagnosed. Women are two to four times as likely to have the illness. Some patients, like Nita Thatcher, are so debilitated they remain mostly homebound for months or years at a time. Doctors often regard the symptoms as psychosomatic, imaginary, or a sign of mental distress. Patients routinely confront disbelief and ridicule from employers, friends, even family members.
The CDC first investigated the illness in the 1980s in Incline Village, a Lake Tahoe resort town in Nevada. One hundred and sixty residents had flocked to local doctors’ offices, suffering from what appeared to be a persistent viral infection resembling mononucleosis or a nasty, non-resolving flu. However, the CDC team did not confirm a viral link. In the 30 years since, federal researchers have failed to identify any causes, diagnostic markers, or drug treatments — an impressive trifecta of non-accomplishment.
Last year, however, the scientific terrain shifted sharply when the U.S. Institute of Medicine and the U.S. National Institutes of Health both released high-profile reports about the illness, based on extensive reviews of the literature. In contrast to the arguments of the British researchers, the reports portrayed ME/CFS as an organic disease marked by major immunological, neurological and cognitive abnormalities.
In fact, the IOM report identified the distinguishing symptom as “exertion intolerance,” another name for post-exertional malaise — a sustained physiological crash that can occur after even minimal amounts of activity. In focusing on this phenomenon, the report confirmed what patients like Nita have long understood — that expending too much energy and ignoring the body’s warning signs only makes them sicker. In other words, continuing to exercise despite an increase in fatigue, pain, and other symptoms could do more harm than good.
“The rigid approach implies that those who get sicker after exercise and can’t continue with GET are somehow to blame, giving up too readily and therefore complicit in the perpetuation of their disability,” Peter Rowe, a Johns Hopkins pediatrics professor and ME/CFS expert who served on the Institute of Medicine panel, wrote in an email.
“The assumption that deconditioning is the cause of all symptoms ignores the potential contribution of other unrecognized biomedical problems (and ignores much of the research produced in the last 20-plus years),” he added.
While the exact causes of ME/CFS have yet to be pinned down, most cases arise after acute infectious illnesses; experts believe that exposures to other physiological insults, such as environmental chemicals or mold, could also play a role. Research has shown that even after the initial event has passed, patients’ immune systems often appear to be in a state of hyperactivation, as if their bodies are still responding to an external threat. In some tests patients also exhibit dramatically reduced levels of energy production when they engage in exercise two days in a row, compared to healthy controls. Genetic susceptibility is also believed to be a factor. Some researchers are exploring whether ongoing infections with known or unknown pathogens play a role. In addition to the recent study on metabolites, scientists from Columbia, Stanford, Cornell, and elsewhere have reported significant findings that could ultimately lead to diagnostic tests and possible drug treatments.
In recent years, the NIH has spent about $5 million annually on researching ME/CFS, far less than for many diseases with far fewer sufferers. Last October, following the release of the two U.S. reports, the agency announced plans to step up its efforts to find answers. “Of the many mysterious human illnesses that science has yet to unravel, ME/CFS has proven to be one of the most challenging,” said NIH Director Francis Collins, in a statement. The agency has since started its own study and says it is looking into other ways to support research.
Nita and other patients welcome the new research but say the government has let them down repeatedly. Without sufficient funding to pursue promising leads, Nita said, the recent initiative “won’t count for diddly squat.”
In any event, Nita recognizes, future advances will not bring back the decades scarred by sickness. She doesn’t usually discuss the issue in such depth, she tells me in one of our 15-minute sessions, so being interviewed is surprisingly emotional for her. “It’s a gut-level confrontation with the disease that I don’t put myself through very often,” she says of our conversations. “Sometimes the sense of loss and alienation from the life that I expected has just grabbed me by the throat and told me ‘This is your reality.’”
Despite the uncertainty over causes and the widespread evidence that exertion can be harmful, the exercise therapy pioneered and promoted by British mental health experts has emerged as the dominant treatment model. The Mayo Clinic, WebMD, Kaiser Permanente, and the CDC, among others, promote it on their websites. (The Cleveland Clinic, where Nita Thatcher is still a patient, highlighted graded exercise therapy in an online training module for the illness, which expired in 2014 and has not been replaced.) The American Academy of Family Physicians and the American College of Physicians endorse the treatment. So do UpToDate, a popular commercial site that provides advice on clinical decision-making, and Healthwise, a nonprofit that disseminates information to medical providers. These sites and organizations generally use the name chronic fatigue syndrome, not ME/CFS.
The most prominent evidence for graded exercise therapy comes from the PACE trial, the focus of my extensive reporting last year. (PACE is the shorthand name for the full title of the study as it appeared in The Lancet: “Comparison of adaptive pacing therapy, cognitive behavior therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome: a randomized trial.”) The PACE investigators reported that both graded exercise therapy and a second treatment, cognitive behavior therapy, were moderately effective in improving symptoms.
The trial’s three principal investigators — psychiatrists Peter White and Michael Sharpe, and behavioral psychologist Trudie Chalder — are highly influential in British academic and medical circles. For many years, they have advised government agencies and insurance companies that their behavioral and cognitive approach to treatment could improve the health of ME/CFS disability claimants and get them back to work. Their ideas have heavily influenced medical treatment and public attitudes towards the illness. They designed the trial hoping to demonstrate that the benefits they were claiming for their treatments were real.
British government agencies spent £5 million ($6 million today) on the trial, which recruited 641 participants from specialized clinics, starting in 2005. Participants were randomized into one of four treatment groups and followed for a year. Besides the groups receiving graded exercise therapy and cognitive behavior therapy, a third group received “adaptive pacing therapy,” an intervention based on the pacing approach. However, in transforming this self-help technique into a structured “therapy” — with diaries and advance planning and a “therapist” providing supervision — the PACE researchers changed it enough to make it difficult to compare to the actual symptom-management strategy used by patients.
Participants in all three intervention arms received up to 15 therapy sessions. They were also offered “specialist medical care” — at least three sessions with a doctor who had expertise in the illness. A comparison group received only the specialist medical care. According to the 2013 paper in Psychological Medicine, 22 percent of those receiving either graded exercise therapy or cognitive behavior therapy “recovered,” about three times the rate in the other two groups.
Unlike large pharmaceutical trials, in which no one knows who is getting the drug and who is getting the placebo, PACE was non-blinded; that is, participants knew which treatment they were receiving and clinicians knew which treatment they were delivering. Non-blinded studies are considered highly vulnerable to bias, especially when the primary outcomes, as in PACE, are subjective.
Cognitive behavior therapy, often called CBT, is designed to help people cope with any number of adversities, including sickness. But PACE presented the therapy differently — as a path toward a full return to health. Like graded exercise therapy, the PACE version of cognitive behavior therapy was geared toward reversing the deconditioning presumed to lie at the heart of the illness. The treatment sought to help participants abandon the belief that they suffered from an organic disease requiring them to rest, at the same time promoting increased activity and a return to regular routines. The various U.S. medical organizations and treatment guidelines, from the CDC and elsewhere, generally recommend cognitive behavior therapy as well as graded exercise.
But the PACE study suffered from such serious flaws that its reported results are uninterpretable and meaningless. Its main claims of success rested on a mind-boggling paradox: In some cases, even if participants got worse during the trial on the two primary outcomes of physical function and fatigue, they could still be deemed “recovered” on these measures. How? Because the investigators’ criteria for “recovery” were so broad that they represented worse health than the entry criteria for serious disability. In fact, 13 percent of the PACE participants qualified simultaneously as being disabled enough to be in the trial, but already “recovered” for physical function or fatigue before any treatment at all — an astonishing fact not disclosed in the published papers. Instead, at the press conference presenting the Lancet paper, co-author Trudie Chalder declared that “twice as many people on graded exercise therapy and cognitive behavior therapy got back to normal.”
In addition to these nonsensical overlapping thresholds for entry and “recovery” on the primary measures of physical function and fatigue, my PACE investigation documented many other flaws, including these:
• After the trial began, the investigators weakened their standards for success by dramatically revising their methods for assessing “improvement” and “recovery,” which bolstered their chances of being able to report positive findings. They did not provide the results they originally promised in their trial protocol nor did they include sensitivity analyses, the standard statistical tests for assessing whether such significant protocol changes produced more favorable results.
• During the study, the investigators published a newsletter for participants that included glowing testimonials from earlier participants about their positive outcomes, potentially biasing the responses of the many remaining subjects.
• While physical functioning and fatigue were subjective outcomes assessed with self-reported questionnaires, the investigators disavowed their own objective measures, like a walking test and employment status, as irrelevant, inaccurate, or otherwise flawed — after all these measures failed to demonstrate “recovery.”
• Even though the investigators promised in their trial protocol to disclose “any possible conflicts of interest” and “institutional affiliations” while obtaining informed consent, they failed to tell prospective participants of their close ties to disability insurers — to whom they had long been promoting the very treatments being studied.
In addition, the PACE investigators identified participants using only a single symptom to diagnose the illness — six months of disabling, medically unexplained fatigue. Other common definitions require multiple symptoms. Last year’s NIH report found that using a broad definition focused on fatigue, as was done in the PACE trial, can generate study populations that include an unknown number of people who do not have ME/CFS but instead suffer from other fatiguing illnesses, including major depressive disorders. (In contrast, ME/CFS patients can suffer from what is often called secondary depression — that is, they are depressed because they have a chronic illness, and especially one that many people deny exists.)
Exercise and psychotherapy are known to benefit people with depression. If participants in an ME/CFS trial are actually suffering from a major depressive disorder but not from ME/CFS, then treatments that benefit them could be misinterpreted as beneficial for ME/CFS patients. Given the difficulty of understanding results from heterogeneous samples, the NIH report concluded that the PACE definition, called the Oxford criteria, could “impair progress and cause harm” and should be “retired” from use. (The PACE trial also included two subgroup analyses of participants defined using more specific definitions, but other researchers have dismissed these subgroup analyses as unreliable.)
In February, as a result of my reporting, 42 scientists, academics and ME/CFS clinicians posted an open letter to The Lancet on Virology Blog, declaring that PACE’s methodological lapses “have no place in published research.” The letter, which I helped to orchestrate, urged the journal to seek a fully independent review of the trial. The investigation also prompted a dozen ME/CFS advocacy groups to warn U.S. health officials that “continuing to use PACE and similar Oxford definition studies to support treatment recommendations for all ME/CFS patients is an issue of grave concern.”
The letter asked them to take steps “to best protect patients.”
In response, the Agency for Healthcare Research and Quality, which had recommended graded exercise therapy and cognitive behavior therapy, recently reversed itself. In a new analysis excluding PACE and other Oxford-criteria studies, the agency found no evidence that graded exercise therapy was effective and minimal evidence for cognitive behavior therapy.
For years, patients have clamored for the PACE investigators to publish the results they promised in their protocol, using their original standards for success. The authors refused. Patients filed requests for anonymized data and other trial documentation under Britain’s freedom-of-information law. Most requests were rejected by Queen Mary University of London, the professional home of lead investigator Peter White.
In September, the university finally released some PACE trial data under a court order involving a freedom-of-information request that a patient had pursued for two years. A small group of patients and academic statisticians analyzed it and published their findings on Virology Blog. And with that, the PACE trial’s 22 percent recovery rates “went up in smoke,” wrote Julie Rehmeyer, a journalist who is also an ME/CFS patient, in a compelling article on how “bad science misled millions” for STAT, a health news site connected to The Boston Globe. In fact, in the new analysis the “recovery” rates fell to single digits, and the results were not statistically significant.
In their own re-analysis of the results, posted online by the university, the authors reported that with the original protocol methods, the graded exercise therapy and cognitive behavior therapy groups were still more likely to produce “improvement” than the other two groups, at a rate of about 20 percent. Patients quickly pointed out that this was a third of the “improvement” rates the PACE team had reported in The Lancet.
Ronald Davis, the renowned Stanford geneticist, told me last year for the Virology Blog investigation that the PACE study “has so many flaws” and that he didn’t “understand how it got through any kind of peer review.” He began investigating ME/CFS himself after his son fell seriously ill a few years ago, and works with the Open Medicine Foundation, a California-based research group focused on the disease. Davis said leading medical organizations and institutions should have scrutinized and assessed the study themselves before adopting its recommendations
“You can’t just say it’s in the literature, so it must be right,” said Davis, who also served on the IOM panel. “You need to read the study and make your own decisions.”
“It shouldn’t have been published,” he added.
Bruce Levin, a Columbia biostatistician who worked with patients on the new “recovery” analysis, reviewed the PACE trial last year at my request and condemned its many methodological lapses. “We all seem to agree that medicine should be based on evidence,” he said in a phone interview for this article. “And if the evidence is faulty, then how can you make guidelines based on faulty evidence?”
To cite the questionable results from PACE as evidence for clinical guidelines, he said, is “ludicrous.”
Levin, Davis, Racaniello, and I are currently seeking additional PACE trial data under the U.K.’s freedom of information law. Queen Mary University of London turned down our request, and we have appealed. Meanwhile, the PACE principal investigators — White, Sharpe and Chalder — did not answer multiple email requests seeking comment for this article. Neither did Richard Horton, editor of The Lancet.
Nita and Doug Thatcher have been together for half a century. For most of that time, she has been ill — sometimes functioning reasonably well, sometimes barely able to get up. Doug is 69, two years older than Nita. Easygoing and self-deprecating with calm gray eyes, he smiles and chuckles when he talks about his wife.
He tells me he is Nita’s “lover, friend, helper.” She calls him “my rock” and “that solid core of warm gold at the center.” She considers herself luckier than many: She’s heard too many stories of people with ME/CFS deserted by spouses, children, friends and colleagues.
Nita was always blessed with “plenty of spizzerinctum,” says Doug. He heard an old preacher use that word once and thought it captured his wife’s sparkle and vitality, the qualities that drew him to her. Doug says he sees the same person when he looks at Nita now. He laughs. “More weight, bless her heart!” Then he adds: “I see the same person, in jail. Confined, sometimes — in solitary confinement.”
Doug and Nita have maintained separate bedrooms for many years. Her illness already made it hard for her to get a good night’s rest, and then his snoring compounded the problem. That did not end their sex life, but Nita’s health once again declined after the move to Ohio. Several years ago, she found that experiencing an orgasm could push her body into a bad relapse, so they stopped having sex. “That’s been hard,” she says wistfully. Luckily, hugging and kissing are still possible. “You just find ways to be intimate,” adds Doug.
She stays as active as she can without exceeding what she knows is her limit. Several times a day, she braves the journey from her recliner to the front door and back. The path snakes through the kitchen, den, and living room. At her best, she can make the trip without a rest. During weaker periods, she leans on countertops, walls and furniture, as needed. The round trip takes about 100 steps. Her current daily maximum is 800 to 1,000.
Like others with the illness who practice pacing, Nita is attuned to her body’s shifting sensations; that’s how she knows when to rest. “I’m a Type A-minus personality,” she says, very much the type to push through difficult situations. (The “minus” helps “to take off the obnoxiousness of being a Type A personality.”) But if your body tells you to stop, she explains, the worst thing someone with ME/CFS can do is try to push through.
Nita has a full, round face and a welcoming gaze. During one of our conversations, she wears a large turquoise robe that billows over the recliner, with a magenta shawl around her shoulders. She sits with her legs stretched forward, crossed at the ankles. In her younger years, with a 36-22-36 figure, she would have been described as buxom. But prolonged inactivity, among other factors, has altered her proportions. These days she weighs 270 pounds — twice what she considers optimum.
“I was not obese till my mid-50s,” she says. She knows the extra weight exacerbates her medical problems. She’s 30 pounds down from what she was at her highest.
Nita can find much of what she needs in the cabinets and drawers on either side of her recliner — sewing items, toiletries, a blood pressure monitor, medication, hair rollers, stationary, pens and pencils, a stapler. Books she might want — about arts and crafts, for example — are within easy reach. The bed and bathroom are each a few steps away, the kitchen only a bit farther. “This is my life now basically,” she says in a voice layered with acceptance, surprise, sadness. “This room.”
The Thatchers have six grandchildren, so some of her shelves are stacked with pop-up books — “20,000 Leagues Under the Sea,” “Star Wars,” books about ancient Egypt, and Pompeii. The grandkids have adapted to her illness, but it pains her that “they know me as a sick grandma — that hurts more than a lot of other things,” she says. “You like to think you pass certain things on to children and grandchildren. I wanted to pass on how to have fun, how to enjoy life. I don’t know if I’ve been successful in that.”
To help her grandkids understand her situation, Nita used a teaching tool she came across online. She spread out a batch of spoons on the floor, explaining that each one represented a certain amount of activity. Healthy people have a lot of spoons they can use every day. Currently, Nita figures she has, at most, 13: fixing a frozen meal uses up a spoon, for example, as does every 15-minute conversation. “You want me to push you around the playground, I need to take three of my spoons,” she told her grandkids. Even the youngest, Hayden — 4 at the time — grasped the concept.
It is hard to overstate how much patients hate the name chronic fatigue syndrome. The reported outbreak in Incline Village in the mid-1980s appeared to be linked in many cases to the Epstein-Barr virus, which causes mononucleosis. But the CDC investigators disputed the role of the pathogen in the cases they reviewed and declined to officially name the illness chronic Epstein-Barr virus syndrome. Instead, in its 1988 paper, the CDC-led team settled on chronic fatigue syndrome.
For patients, the name designated by the CDC has been a disaster. For one thing, it conflates “chronic fatigue,” which is a symptom of many conditions, with the specific illness known as “chronic fatigue syndrome,” creating the false impression that the latter is essentially an extended case of the former. Moreover, the common meaning of the word “fatigue” does not come close to conveying the paralyzing exhaustion that patients routinely describe. Because of these misunderstandings, patients say the name has distorted public perceptions and affected how their doctors treat them, how much money is spent on research, and how their families and friends respond.
Laura Hillenbrand, author of the best-sellers “Seabiscuit” and “Unbroken,” and probably the best-known person with the disease, has called the name “condescending” and “misleading.” “The average person who has this disease, before they got it, we were not lazy people,” she told The New York Times in 2011. “This disease leaves people bedridden. I’ve gone through phases where I couldn’t roll over in bed. I couldn’t speak. To have it called ‘fatigue’ is a gross misnomer.”
Beyond the name, the issue of how to define the illness has bedeviled the field and hampered research. In 1994, a CDC-led team published the most widely used definition. To receive a diagnosis, patients must have experienced six months of unexplained, disabling fatigue, as in the Oxford criteria used in the PACE trial. However, they must also display any four of eight other symptoms: post-exertional malaise, unrefreshing sleep, problems with memory or concentration, muscle pain, joint pain, headaches, tender lymph nodes, and sore throat.
Although the CDC definition, unlike the Oxford criteria, requires multiple symptoms, many experts have still criticized it as imprecise. They argue that several of those eight symptoms — such as post-exertional malaise, unrefreshing sleep, and problems with memory or concentration (or other cognitive functions) — are central to the disease and should be required, not optional. Many patients and clinicians prefer two more detailed and precise definitions published in 2003 and 2011.
Ever since the CDC coined the unpopular name, patients and advocates have faulted the U.S. government’s incompetent response. In “Osler’s Web,” a prodigious feat of investigative reporting published in 1996, the journalist Hillary Johnson documented how top health officials dismissed the significance of the illness and neglected promising leads. In the late 1990s, the CDC was found to have diverted tens of millions of dollars that Congress had designated for chronic fatigue syndrome into other programs. In the 2000s, the agency focused on stress-related and psychological aspects of the disorder, to the dismay of patients. A much-ridiculed paper in the journal Psychotherapy and Psychosomatics asserted that patients suffered from “maladaptive personality features,” and in particular from higher rates of “paranoid, schizoid, avoidant, obsessive-compulsive, and depressive personality disorders.”
Since 2012, the CDC has been conducting a study designed to gather standardized medical information on as many as 450 patients, drawn from the practices of several clinicians experienced at treating ME/CFS. The agency hopes the results will more clearly define the disorder, identify possible subgroups, and illuminate the underlying physiology, but to date no actionable information has been published.
Nita and Doug both grew up in strict religious homes, and both learned to question the unforgiving doctrines and literalist biblical beliefs their families tried to instill. She met him when she was 11, at a church summer camp. (“Oh, my Lord, what was Nita like when I met her? A stringbean, a wiry, vivacious young lady,” recalls Doug.) They began dating six years later, in 1966. As a high school senior, she chafed under her mother’s strict control. He was already off in college. The week after graduation, she left home to be near him and escape her mother’s dictates.
Although the couple shared a strong emotional and physical bond, and got engaged quickly, Nita insisted on delaying the wedding for more than a year, to make sure Doug would respect her as an equal partner. “I grew up with a strong reliance on my own intellect and a great deal of determination not to be dominated or manipulated,” she says now.
They married in the summer of 1968. Instead of continuing with college, Nita worked to support her husband’s studies, first in Michigan and then in Oklahoma, where he attended divinity school. Within a few years, they had two young children — Julie, born in 1971, and John, born two years later.
Many ME/CFS patients can identify a particular point when their illness began. They got sick from an acute viral infection or something else — and then when they should have gotten better, they didn’t. But some people, like Nita, report a more gradual decline. A few years after she married Doug, she experienced a terrible bout of flu, followed by her difficult second pregnancy. She recovered from both. But afterwards, in her late 20s, she started to drag. She never seemed to have as much energy as she should.
She noticed it especially while playing volleyball and tennis — two favorite pursuits. She felt sluggish, always slow to reach the ball. Then the muscle aches started. And she began having trouble getting a refreshing night’s rest. The doctors couldn’t figure it out. The tests all came back negative. For several years, she took medication to help her sleep. Then the medication stopped working.
Nita managed, more or less, for the next 15 years. She learned to rest when she needed to. Sometimes her energy levels improved for months at a time, and she was able to hike and camp out, within limits. She wrote and directed some church musicals and community theater productions, always struggling but managing somehow.
As her illness fluctuated, Nita adapted to its rhythms. For a while she took college classes again, then realized she was overdoing it — she still had two little kids around — and stopped. In the early 1980s, she recovered enough to work full time in the auto-financing industry, reviewing contracts. Then she got worse again and quit. Later still, she started her own costume-making business; she loved the work, and being her own boss allowed her to control the hours. And always, Doug was willing to pick up the slack. “I knew she had a lot more limitations and was dealing with something serious and mysterious,” he says.
Nita kept seeking out information and answers. She recalls that at one point in 1989, she was listening to a talk show and heard about a new illness called chronic fatigue syndrome. The description sounded similar to what she had been experiencing for more than a decade. But she thought the name was insulting, trivializing — “like a slap in the face.”
In 1989, the year after the CDC-led team selected the term chronic fatigue syndrome, four British researchers — Simon Wessely, a psychiatrist; Trudie Chalder, the psychologist and future PACE investigator; and two colleagues — proposed an explanation for the ongoing disability of patients with the condition.
“A model is outlined of an acute illness giving way to a chronic fatigue state in which symptoms are perpetuated by a cycle of inactivity, deterioration in exercise tolerance and further symptoms,” they wrote in the Journal of the Royal College of General Practitioners. “This is compounded by the depressive illness that is often part of the syndrome. The result is a self-perpetuating cycle of exercise avoidance.”
Because patients were presumed to wrongly believe that they suffered from a medical disease, the authors proposed treatments that focused on both psychological and behavioral approaches. “Cognitive therapy helps the patient understand how genuine symptoms arise from the frequent combination of physical inactivity and depression, rather than continuing infection, while a behavioral approach enables the treatment of avoidance behavior and a gradual return to normal physical activity,” they wrote.
Wessely, Chalder, and their colleagues — including White and Sharpe, Chalder’s PACE co-investigators — have since collectively written hundreds of articles, studies, and reports, a great many of them promoting what they call the “biopsychosocial” theory of the illness, focused on false cognitions, avoidance of exercise, and deconditioning. They have attained leading positions at well-known academic and medical institutions. They have also cultivated close consulting and financial relationships with British health agencies as well as disability insurance companies. (Wessely was deeply involved with PACE but is not a co-author. He is considered a founder of the cognitive-behavioral approach to treating ME/CFS and is currently president of the Royal College of Psychiatrists, the U.K.’s national professional association.)
These mental health professionals have long blamed what they call the “M.E. lobby” — that is, patient activists and advocacy groups — for enabling, supporting, and reinforcing claimants’ delusions of having an ongoing, unresolved disease. The provision of state and private disability benefits, and other financial, social and psychological factors, Sharpe wrote in a 2002 UNUMProvident report on disability insurance trends, could also impede both the patient’s own recovery and the effort to resolve insurance claims.
“A strong belief and preoccupation that one has a ‘medical disease’ and a helpless and passive attitude to coping is associated with persistent disability,” Sharpe warned in the report.
“The current system of state benefits, insurance payments and litigation remain potentially major obstacles to effective rehabilitation,” he wrote.
Some early studies from these and other investigators showed that treating patients with cognitive and behavioral therapies could improve subjective responses on questionnaires about fatigue, physical function, and other health indicators. However, results for objective measures of improved function proved disappointing. In 2003, the Medical Research Council, a U.K. government body that supports health research, announced that it would fund a clinical trial to determine once and for all which treatments were effective. Three other government agencies agreed to contribute funding, among them the Department for Work and Pensions, charged with handling state disability issues.
The work and ideas of these British clinicians have had a major impact on treatment, and not just in Britain. Over the years, they have collaborated closely with experts at the NIH and CDC. The flood of studies and papers they produced throughout the 1990s touting their theory and approach found a receptive audience among U.S. health officials and medical professionals.
Mary Dimmock, a former scientist and business analyst at Pfizer who became a patient advocate after her son fell ill, has researched the development of U.S. health care policy toward ME/CFS. “At least by the early 1990s, key players in research in the U.S. had embraced the idea of [false] illness beliefs and deconditioning,” she said in a phone interview. By the mid-1990s, she added, clinical guidelines for doctors began placing a “heavy emphasis” on graded exercise therapy and cognitive behavior therapy.
Dimmock and her son, Matthew Lazell-Fairman, have documented the government’s decades of neglect of the illness in a self-published report, “Thirty Years of Disdain: How HHS and a Group of Psychiatrists Buried Myalgic Encephalomyelitis.”
In the mid-1990s, after years of suffering from the extended and unexplained lapses in energy, Nita, then in her 40s, finally received an official diagnosis. Her doctor had already told her he believed, as did she, that she had the illness she’d heard about — chronic fatigue syndrome. By then, the term had become widely known, although the condition was commonly derided as “yuppie flu.”
The doctor referred her to a local psychiatrist, who ruled out depression as a cause and formally identified her condition. Then he told Nita the good news: British experts had found that patients improved significantly after a regimen of gradually increasing exercise. He sent her to a physical therapist familiar with the technique. “It was all the rage in the U.K., according to the therapist, and showing great results,” she says. “He was gung-ho on it.”
Nita was skeptical. At this point, she felt she was operating at about half her pre-illness energy level — not great, but good enough. She made sure to take two eight-minute walks a day. That was as much exercise as she felt her body could handle, and she feared testing the limits. But her primary care doctor also urged her to give the treatment a chance, and the psychiatrist insisted it would help her, so she agreed.
The physical therapist directed her to increase the twice-daily walks to as long as 15 minutes over the course of six weeks, and to add resistance and stretching exercises. She followed his instructions but felt she was sliding downhill. “After three weeks, I said, ‘I don’t know if I can handle it — the pain is worse, the fatigue is worse,’” she recalls. “He said, ‘We just need to tweak it.’ He said, ‘This is working really well in the U.K. and it will work for you.’”
But after more weeks of dragging herself through a shortened exercise regimen, she suffered a complete crash. Her body refused to do more, and she quit the program. The physical therapist would not sign documents supporting Nita’s request to seek disability. He insisted she keep going, that she needed to stick with the routine. “I just about told him where he could shove that,” she says.
The psychiatrist also refused to sign any disability forms. “He told me he wouldn’t be helping me with disability because I wasn’t trying to get well with a proven course of action,” she explained in an email. Her primary care doctor knew she’d given the exercise program a serious chance, so he was willing to sign the required documents.
The post-exercise crash knocked Nita way below her previous middling level — to about 15 percent of her pre-illness state, she estimates. She stopped her various activities and mostly rested, sparing time only for family visits. Gradually, over two or three years, she regained some of the energy she’d had before the crash. But she never regained it all.
She could no longer play softball or tennis, but she was once again able to participate in local theater groups. She didn’t have the strength to sew all the costumes, but she still loved to design them. And best of all, she found herself able to hike and camp again, as long as she made sure to take long rests.
While Nita and others have found that pacing helps control their symptom flare-ups, the PACE results convinced many medical authorities that the strategy doesn’t work — even though the trial did not test pacing as a self-help technique but instead assessed the investigators’ highly structured version of it. Meanwhile, graded exercise and cognitive behavior therapy continue to be widely recommended.
In the summer of 2015, experts at the Mayo Clinic in Rochester, Minnesota, told Rachel Riggs, a San Diego entrepreneur and business consultant who had suffered from exhaustion and other symptoms for years, that she had chronic fatigue syndrome. The Mayo website recommends graded exercise and cognitive behavior therapy. But instead of entering the clinic’s own rehabilitation program, which included activities designed to counter deconditioning, Riggs asked for advice on pursuing a home-based regimen modeled on the Mayo approach instead. She followed the instructions carefully, she says, alternating between aerobic exercise and yoga — and relapsed badly after a month.
“Total zombie,” she recalled in a recent Facebook exchange. “I was having trouble thinking and processing complex ideas, and severe sensitivity to any stimulus. … If someone sneezed unexpectedly, it was as though I was on the firing squad in Afghanistan.”
In desperation, she decided to enroll in Mayo’s rehabilitation program after all — and then, just before leaving home, conducted some online research. For the first time, she read about post-exertional malaise and the controversies surrounding the PACE trial. So she canceled the Mayo program and sought treatment with well-regarded ME/CFS specialists instead. Although somewhat improved after months of rest and treatment with an immune modulator, she has still not recovered her pre-crash level of function.
She used to walk 20 minutes every morning, but that remains beyond her current capabilities. With the crash, she also suffered some loss in cognitive function. “My brain has been toast since then,” she wrote. “I feel as though I have lost about 20 I.Q. points.”
Obtaining satisfactory responses (or any responses at all) from medical institutions about the PACE trial is surprisingly challenging. Despite its prominence, no one appears willing to defend it directly.
Eileen Sheil, a spokeswoman for the Cleveland Clinic, confirmed that the medical center no longer offers the online training module promoting GET and CBT. But she failed to respond to repeated requests for information about the clinic’s current treatment protocol. Kaiser Permanente, UpToDate and Healthwise did not respond to multiple requests for information about their continued support for the PACE interventions. A spokeswoman for the Mayo Clinic emailed that “we are not interested in participating in your story.”
In response to questions about the study’s documented flaws, the CDC’s Division of High Consequence Pathogens and Pathology, which oversees ME/CFS, emailed a statement explaining that the agency “was not involved in the PACE trial and is therefore unable to offer its opinion on its efficacy or integrity.” The statement did not explain why the agency’s non-involvement in PACE automatically neutered its ability to assess the integrity of a study in which some participants were already “recovered” on the primary measures at the start.
The CDC statement also noted that the agency “is committed to providing guidance based on the most up-to-date, evidence-based science available.” Yet it did not explain why the website still recommends treatments — specifically graded exercise and cognitive behavior therapy — for which the main evidence comes from PACE and other studies using the Oxford criteria. Among the most “up-to-date, evidence-based science available” about Oxford criteria studies comes from last year’s NIH report, which found that they could “impair progress and cause harm” because the samples included people without ME/CFS.
Mary Dimmock, the patient advocate and former pharmaceutical scientist, has repeatedly complained to federal health authorities that the treatment recommendations are based on lumping together incompatible studies.
“Evidence-based guidelines should be based on studies in patients who actually have the disease for which the guidelines are being developed,” she said in a phone interview. “But if you mix and match the results from studies that don’t include the same set of patients, then the treatment recommendations that you develop are not necessarily valid for the group of patients they’re intended for. It would be like developing cancer recommendations based on heart patients.”
One afternoon, while Nita rests, Doug is sitting on the white wicker chair on the front porch, smoking a Pall Mall. Doug has diabetes. He knows smoking isn’t good for him, and it bothers him that he can’t quit.
After 40 years serving multiple congregations in Oklahoma, Doug is glad to be back in Ohio. He hopes to see more of their family. Their daughter, a property manager, lives with her family in Columbus, an easy drive to Lorain. Their son, his wife, and their kids had also moved to Ohio in 2009, but they are now living back in Oklahoma.
Doug tells me he has always made sure to maintain his own interests, and he continues to do so in retirement. He plays tennis. He hangs out with friends. He tends his collection of hundreds of vinyl records, browsing in record shops and attending flea markets and record conventions. Like his wife and both kids, he is a big Queen fan.
I ask Doug how Nita’s illness has affected him, and how he has reconciled their situation with his faith. He’s never been prone to depression, says Doug, and it’s not his nature to worry much about the future. But dealing with Nita’s situation has forced him to become much more patient over the years. It’s also forced him to be a better cook, he says with a chuckle.
And despite Nita’s disability, he marvels at her spirit and ability to cope. “She’s able to maintain an equilibrium and balance in the midst of all this that I think is highly unusual for being so limited,” he says, his voice tinged with awe. “She accepts what she’s got, but she’s not caving in to it.”
As for his faith, it has always been “a questioning faith,” he says. “God in our view is big enough that we can shake our fists once in a while,” he says. “It’s OK to cuss and say, ‘What the hell are you doing to me?’ If God’s not big enough to be questioned or screamed at, then God’s not big enough.”
Mostly, he and Nita have managed to adjust their lives to the changing circumstances. Usually he’s reconciled to it. But not always. Human beings are good at feeling sorry for themselves and holding “a pity party,” he says, and he’s no exception. “There are a few times when I feel I really don’t like all this being on my shoulders,” he says. “I experience that thought from time to time: ‘That sucks!’ So I say it out loud, and it’s over.”
For her part, Nita knows that her health could continue to decline. She knows something could happen to Doug. She’s a pragmatist. From her recliner, she has mapped out and priced possible future living arrangements. She knows many things are not within her control, but she remains determined, she says, to seek “as much joy as I can,” despite her circumstances. “I have enough faith in myself” — she pats her chest — “that I’ll find a way. I’m not sure how. But I’ve done it so far, and I’ll keep doing it.”
David Tuller is a lecturer in public health and journalism at the University of California, Berkeley. He has been a staff reporter and editor at both The San Francisco Chronicle and Salon.com, and he has been a frequent contributor to The New York Times and other publications. At Berkeley, he receives support from a Kaiser Permanente grant to the Graduate School of Journalism.