This is Part 4 of a four-part article on NIH’s Effort Preference claim.

Part 1 can be found here.

Part 2 can be found here.

Part 3 can be found here.

Readers who are not intricately familiar with ME history and politics might ask themselves how we got here. How is it possible that investigators with a glaring bias were allowed to be in a position to abuse this study to confirm their prejudices, set ME research back, and further damage the reputation of ME patients, leading to great harm?

A Short History of the Study

HHS hijacked CFSAC recommendation. The groundwork for the study was laid when the Department of Health and Human Services (HHS) hijacked the October 2012 recommendation by the Federal Advisory Committee (CFSAC) to the HHS Secretary. CFSAC recommended that the Secretary “promptly convene . . . at least one stakeholders’ ([ME] experts, patients, advocates) workshop in consultation with CFSAC members to reach a consensus for a case definition useful for research, diagnosis and treatment of [ME] beginning with the 2003 Canadian Consensus Criteria [CCC] for discussion purposes.”

The CCC, published in a peer-reviewed journal, were developed by an international group of scientists and clinicians with substantial expertise in ME research and treatment. Obviously, the CFSAC voting members had intended for the workshop to endorse or build upon the CCC as clinical and research criteria, which would have been a watershed moment for ME because it would have put an end to the use of the non-specific Fukuda definition in research and for clinical diagnosis, ensuring quality research and accurate diagnoses in clinical settings.

The Secretary basically never followed CFSAC recommendations, and she did not do so here. However, this recommendation was immensely threatening to her and others at HHS. Unlike with government definitions, such as the Reeves and the Fukuda definitions, HHS had had no control over or even input in the CCC, which is why that definition is so much more accurate and specific to ME  than any HHS-sponsored criteria. The universal adoption and endorsement of the CCC would have also lent substantial legitimacy to ME. The fear of HHS officials at the time was palpable. HHS had for decades waged a prodigious disinformation campaign against ME, leading to unrelenting suffering of ME patients. Having to course-correct HHS’s position on ME by accepting the experts’ definition would have been publicly humiliating. Careers were on the line, including careers of high-ranking officials. There was a discernible sense of aggressive urgency at HHS to quash the CCC momentum that had been building due to the CFSAC recommendation and other CFSAC work, an urgency that was highly unusual at the bureaucratic mammoth that is HHS.

As a result, HHS began tampering with the CCC recommendation. The concern at HHS was so grave that three CFSAC members—Ms. Eileen Holderman, the late Dr. Mary Ann Fletcher, and a third individual—were threatened by the CFSAC Designated Federal Officer (DFO), HHS’s Dr. Nancy Lee, with eviction from the committee for voicing their opinions. Ms. Holderman, who was the advocate on CFSAC at the time, chaired two CFSAC sub-committees, and was a member of the CFSAC Leadership committee, was removed from the CFSAC Leadership Committee in retaliation for her championing the experts’ workshop and the CCC, leaving that committee without patient input. Below is a clip of the CFSAC meeting during which Ms. Holderman and Dr. Fletcher went public with the intimidation and threats.

The shameful conduct by Dr. Gailen Marshall at the meeting was off the charts. Marshall was a med-school buddy of Lee who was willing to do HHS’s bidding, which landed him the gig as CFSAC chair. (HHS nepotism is legendary. Take a look at the Acknowledgements paragraph in the intramural paper.) When Ms. Holderman pointed out that the important case-definition issue deserved appropriate time for discussion, a position that cannot possibly be controversial, Marshall punished her by cutting her time to comment from three minutes to two minutes while he gave NIH’s Dr. Susan Maier, who was not a voting member, all the time she wanted for a surreal patient-hostile rant. Any dissent by HHS outsiders, no matter how valid or justified, will have consequences at HHS as confirmed recently by Nath, principal investigator of the intramural study; more on that below. It was stunning to watch Marshall’s, Lee’s, and Maier’s complete indifference and stone-cold faces when Ms. Holderman and Dr. Fletcher reported the DFO’s threats and intimidation to the committee. All Marshall had in him was an emotionally dead, “ok.” Being an HHS loyalist, Marshall’s only concern was to shut down the case-definition discussion, potentially the most important discussion CFSAC ever had, as quickly as possible. This constituted an enormous abuse of power, which Marshall seemed to relish.

Also pay close attention to the completely unprofessional, deeply resentful, and manipulative moaning by Maier about having had to work “every single freakin’ weekend.” There is a toxic victim-complex culture at NIH where NIH staffers clearly loathe the patients on whose behalf they claim to work, compensated with taxpayer money. NIH staffers seem to be viewing their jobs as doing patients a favor. Never mind that, without patients, there would be no mortgage-covering paycheck for them, but patients better not expect any results from NIH, and they certainly better not voice any criticism whatsoever even after decades of complete failure of the agency to advance ME science and even setting it back. I do not know a single ME patient who would not trade their living death for working on weekends. Nath, too, has for years whined to patients about his workload, which I will address further below.

The advocacy community stood firmly behind Ms. Holderman after she disclosed the government threats. Advocates filed a complaint with HHS’s General Counsel. The ensuing HHS investigation was a farce culminating in a perfunctory and dismissive response by the Assistant HHS Secretary. Nothing to see here. HHS business as usual.

Instead of following the CFSAC recommendation, the HHS Secretary and HHS component agencies misappropriated the recommendation when they used it as cover to urgently enter into a contract with the IOM (now NAM), funded by NIH, for yet another non-specific ME definition. Even though the CFSAC recommendation covered both clinical and research criteria, the IOM contract was limited to:

“evidence-based clinical diagnostic criteria for [ME] for use by clinicians.” [emphasis added]

HHS spent a million dollars on procuring the IOM criteria, which is another indicator as to how concerned the Secretary and others at HHS were about the CCC, a definition that was readily available and free. This purchase was the polar opposite of what CFASC had recommended. Instead of involving experts in the field, the IOM was hired by HHS, and instead of covering both clinical and research criteria, the IOM contract addressed only the clinical diagnosis. CFSAC was completely shut out of this process. The alleged reason for proceeding with the IOM was that HHS does not endorse or create disease definitions, a blatant lie as the agency had done it numerous times for ME.

By doing this, the Secretary disregarded a protest letter addressed to her by a total of 50 ME national and international researchers and clinicians endorsing the CCC for research and clinical diagnosis and urging HHS to exclusively use the CCC throughout HHS and its component agencies and programs:

“As leading researchers and clinicians in the field, however, we are in agreement that there is sufficient evidence and experience to adopt the CCC now for research and clinical purposes, and that failure to do so will significantly impede research and harm patient care. This step will facilitate our efforts to define the biomarkers, which will be used to further refine the case definition in the future.

“We strongly urge the Department of Health and Human Services (HHS) to follow our lead by using the CCC as the sole case definition for ME/CFS in all of the Department’s activities related to this disease.”

The experts also strongly opposed the engagement of the IOM and warned that engaging IOM non-experts would set science back, which is exactly what happened:

“In addition, we strongly urge you to abandon efforts to reach out to groups such as the Institute of Medicine (IOM) that lack the needed expertise to develop “clinical diagnostic criteria” for [ME]. … [T]his effort threatens to move [ME] science backward by engaging non-experts in the development of a case definition for a complex disease about which they are not knowledgeable.”

The advocacy community staunchly supported the ME experts with their own letter to the HHS Secretary, signed by 171 ME advocates. The community protest of the IOM definition was fierce and unprecedented.

The community has continued its protest of the IOM definition to this day and for very good reason. About half of the IOM committee consisted of individuals who were not experts in the field, which had been a major concern of CFSAC. The criteria that the panel authored are extremely broad, as the committee intentionally erred on the side of over-inclusiveness. Since the existence of PEM is rarely objectively confirmed by clinicians for a number of reasons, this results in a large number of misdiagnosed patients who suffer from a disease other than ME but are captured by the IOM criteria. Those patients could get effective treatment for their disease. Instead, they are languishing without any help. It is also harmful to actual ME patients when misdiagnosed patients benefit from exercise, psychotherapy, antidepressants, for example, reinforcing the prejudices that many practitioners harbor against ME patients as the result of HHS’s false characterization of ME. It is easy to falsely answer in the affirmative when questioned about PEM as most who do not experience post-exertional fall-out would have an incorrect understanding of it. Feeling worse after exertion without rising to the level of PEM, which is common in deconditioned individuals and certain diseases, is easily mistaken for PEM. In addition, the IOM criteria do not have any exclusions whatsoever, making their use in research fatal.

The IOM criteria are expressly and importantly limited to clinical diagnosis, i.e, they are not to be used for research. HHS’s purported reason for limiting the IOM contract to clinical criteria contrary to the CFSAC recommendation was that a new government research definition would follow, which, of course, never happened. This bait and switch was an evil stroke of genius because the IOM committee predictably delivered very broad criteria, making them unfit for research. Also predictably, researchers have nevertheless proceeded with conducting research on ME patient cohorts selected via the IOM definition with devastating consequences in the form of tainted research, which advocates had warned about from the very beginning. It is almost as though this was HHS’s plan from the start. The best way to prevent progress in a disease is to ensure the use of over-inclusive criteria in research. Of course, HHS knows this, so draw your own conclusions. It is noteworthy that none of the IOM definition authors have protested the improper use of their criteria in research. At least some extramural researchers likely have felt that they had no choice but to use the IOM criteria if they wanted to have a chance of obtaining NIH funding.

Of course, the NIH investigators were not faced with such an ethical dilemma. They were free to use appropriate research criteria without risking funding, but they nevertheless chose the IOM definition as one of three definitions. As discussed in Part 3, the IOM definition is so broad that all 17 ME patients in the NIH study satisfied it while only about half of the patients satisfied the stricter CCC, the definition ME experts and advocates had endorsed. The IOM definition is even broader than the Fukuda definition, which was satisfied by 82% of the patients in the NIH study.

Once the IOM published its redefinition of ME in 2015, it did not take long for CFSAC to be disbanded as it no longer had any usefulness for HHS. The table was set for the NIH study, which was announced shortly thereafter and, indeed, selected patients using the IOM definition (in addition to the not much better Fukuda definition and the CCC).

Collins roped in Nath. In September 2015, then NIH Director, Dr. Francis Collins, under increasing pressure from Congress and the ME advocacy community to cease stalling and obstructing ME research, gave an unsuspecting and unenthusiastic Dr. Avindra Nath, NIH senior investigator and NINDS intramural clinical director, no choice when Collins put the screws on him to spearhead the first NIH intramural study of ME in decades. Nath incessantly tells everybody who will listen that his plate was already full at the time and that he had no room in his busy schedule to take on this study on top of his other research.

Walitt volunteered. Nath was eager to dump this study into somebody else’s lap. Enter Dr. Brian Walitt, who was all too happy to come to Nath’s rescue by volunteering to run the study. Having recently joined the scientific big leagues of NIH, Walitt seized the chance to characterize ME in accordance with his prejudicial beliefs with the weight of the most powerful platform in the global bio-medical research world behind him, which he knew would have a significantly more potent impact than his previous abhorrent research missives about ME and Fibromyalgia.

Walitt is on record with his alleged conviction that ME and Fibromyalgia are identical. “The complaint that predominates your existence is how you end up being named, which has nothing to do with your physiology,” he said while he smirked and gesticulated in an effort to cultivate trust and familiarity with the audience to sell his defamatory and harmful views on ME and Fibromyalgia. Nath was not bothered by Walitt’s highly prejudicial and long-since disproved view that ME is merely a normal life experience instead of a medical entity (see Part 1) and appointed Walitt as lead associate investigator, who would end up designing the study and running its day-to-day activities, freeing up Nath to devote his time to research he obviously deemed more deserving. Nath became senior author of the paper, and Walitt became first author. Walitt’s role in the study gave him staggering power over a group of patients by whom he is so clearly repelled and whose disease he has dismissed and labeled in derogatory ways.

For Walitt, volunteering for the study was a double win: he would have a major impact on the direction of ME research at NIH and, therefore, worldwide (steering it toward the biopsychosocial narrative), and this study would open the door for him to build inter-agency connections due to the large number of scientists, clinicians, and institutes involved in the study, elevating his profile at NIH. It cannot be overstated how much this study boosted Walitt’s NIH career almost immediately after he joined the agency. Nath’s and Walitt’s relationship has been a symbiotic one.

Community protest. Once advocates learned of NIH’s planned intramural ME study eight years ago, they fiercely opposed a number of highly problematic aspects of it, including the involvement of Walitt and other like-minded NIH researchers, the planned use of the Reeves Criteria, a ridiculously broad Centers for Disease Control (CDC) definition of ME, the use of the IOM criteria, the inclusion of Chronic Lyme Disease patients and of patients with Functional Movement Disorder as control groups, etc. Advocates were able to mitigate some of the issues with the study design and staff, but mostly NIH scoffed at the protests and proceeded as planned.

Effort Preference. When NIH signaled indifference regarding the advocates’ protests in 2016, the writing was on the wall that the intramural ME study would emerge with a harmful characterization for ME; the only question was which one. That characterization turned out to be “altered Effort Preference.”

Nath’s Dereliction of Duty and Unprofessional Conduct

Nath presents himself as an aggrieved, innocent, hard-working civil-servant researcher while he has allowed, enabled, perpetuated, and even expanded a systemic pattern of anti-ME bias. His furious defensiveness is likely a personalized outgrowth of the weaponization of the “unworthy-sick” construct that Straus introduced on this side of the Atlantic with respect to ME patients. Nath feels entitled to dismiss and attack advocates precisely because that is what NIH has always done. Straus, for example, was verbally violent and threatening toward ME patients. Nath seems to resort to bitter fury because he has absorbed the NIH culture that patients better be grateful or else.

Nath seems entirely unconcerned with the fact that the alleged EEfRT findings, including the various misrepresentations and misinterpretations, etc., do not support the claims made in the paper with respect to the effort discounting of ME patients, which he, as principal investigator, is fully responsible for. One of two things must be true: either Walitt and/or Madian manipulated Nath and made him look like a fool with respect to the unsupported EEfRT claims, or there is no daylight between Nath and Walitt. Personally, my money is on the latter. In fact, it appears as if Nath himself is a disciple of the biopsychosocial school. This is supported by Nath’s attendance of a symposium on the biopsychosocial aspects of Long COVID in Finland last year as reported by David Tuller. There is no chance that Nath did not realize that his attendance, as an NIH representative and principal investigator of an NIH study on ME, would lend enormous credibility to the biopsychosocial theory of ME, which indicates that he’s fully on board with the Walitt agenda and which would explain the NIH paper’s redefinition of ME in accordance with the ME propaganda of Wessely, who has been propped up by HHS for decades. All of this makes it exceedingly unlikely that  Nath is unaware of what was done to the EEfRT data and of the serious issues I have pointed out regarding the EEfRT testing in Part 2 and elsewhere in this four-part article.

Nath’s attitude toward the community and the study. Nath has been hostile, condescending, disdainful, and manipulative toward the community from the very beginning of this study. For example, he shamefully used a slide listing the study team members that he derisively entitled “Team Tired.”

Watch Nath’s irritated reaction to a petition started by @meadvocacy_org and signed by hundreds of medical professionals and ME advocates and patients asking NIH to cancel the then-planned intramural study due to serious concerns by the community. The petition deserved genuine consideration, but all Nath could muster was annoyance. What was important to him was his own inconvenience and embarrassment, not the impact a botched NIH study would have on the lives of millions worldwide.

By his own accounts, Nath has been perturbed about being expected to take on the ME study without compensation, as he frequently puts it. He frames this as having been forced to donate his time. Just like Maier, Nath seems unfamiliar with the concept of salaried employees. More importantly, Nath’s relentlessly raising this issue is a tell that he did not want to be part of this study, has felt resentful about it for almost nine years, and feels that he has been magnanimous by being involved at all, which again eerily mirrors Maier’s attitude. As far as a preference for effort goes, Nath clearly prefers to put no effort into even pretending that this study has ever been a priority for him. To the contrary, he keeps stressing that hardly any of the involved investigators had bandwidth for this study. He somehow feels that this makes him and his colleagues look good.

This has, of course, directly impacted the outcome of this study. Nobody does their best work when they resent the work, especially when they also do not have any time for it. As the adage goes, the fish rots from the head, and an attitude such as Nath’s would have inevitably negatively affected the quality of the work by other NIH staffers on this study. Nevertheless, Nath recently called it “probably the best study that’s ever been done.” That self-aggrandizing statement is categorically untrue as I have shown. Aside from illusory statements about this study, which patients are supposed to just accept despite enormous issues with the study design and implementation, Nath has little to show for himself when it comes to ME after this tiny study using badly selected cohorts failed to find many well-established abnormalities in ME patients, such as orthostatic intolerance, low Natural Killer Cell function, reactivated viruses, and cognitive dysfunction to name just a few, and the completely bastardized EEfRT analysis is certainly an ugly stain on Nath’s ME record. I would be remiss not to mention Nath’s recent Time100 Health Most Influential People mention for his involvement in ME, a disease whose true nature he and the investigators he supervised obfuscated; the Time100 Health profile of Nath describes ME as a “condition characterized by extreme fatigue.” Q.E.D.

NIH’s timing of the May 2, 2024 Symposium on the study to coincide with the announcement of Nath’s recognition felt like a desperate and transparent attempt to prop up the study. One thing is for sure, this study has been career-advancing for several people at NIH while advocates have had to sacrifice their health in their effort to get the study retracted. With few exceptions, it is advocates who work without compensation, not Nath, who is well compensated.

Nath’s temper and attempts to intimidate advocates. NIH’s hiring of Walitt is likely indicative of an agency-wide agenda and not an accident, but Walitt’s capture of the intramural ME study happened on Nath’s watch. Advocates and patients have shown super-human restraint under the circumstances, not just with respect to this study but over decades given the malfeasance of federal health agencies with respect to ME. Nath, on the other hand, seems to be on a hair trigger when it comes to ME advocacy. During the recent NIH Symposium on the intramural study, Dr. Team Tired had the audacity to accuse ME advocates of causing NIH researchers “pain and suffering” by criticizing their research (at 22:18). Without a shimmer of self-awareness or a smidgen of consideration for what ME patients have endured at the hands of HHS and its component agencies for decades, Nath went full-blown DARVO. This is somebody who is obviously not used to having to answer for his actions. This adage comes to mind:

“When you’re accustomed to privilege, equality feels like oppression.”

We all have watched the suffering of ME patients, including children, and many of us have lost numerous friends to this disease over the years, but we had to listen to a senior NIH bureaucrat whine about his own pain and suffering and that of Walitt?! Nath, a high-ranking federal-health official, quite literally feels persecuted by extremely sick advocates while patients are suffering and even dying as the result of decades of government mistreatment and neglect and while he advances his career. It is obscene.

Nath’s anger is entirely misdirected; it is not the patients’ fault that NIH has held their bodies hostage for decades by not undertaking or funding ME research and that Collins put Nath and his colleagues in the position of having had to squeeze their ME work into their lunch breaks, which, by the way, explains why this study took more than eight years and why the resulting paper, “Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome,” is as ghastly as it is. The embarrassingly large number of mistakes with respect to the EEfRT findings (see part 2) illustrates that the authors did not even proofread their paper.

It is important to see Nath’s accusation of pain and suffering allegedly inflicted on him and his colleagues in another context. Wessely & Co. have accused ME patients of threats that were never substantiated but caused serious reputational harm. Nath has now taken this very page out of Wessely’s playbook.

Listen as Nath loses his cool when powerhouse advocate Ms. Holderman politely asked Nath to make sure that the researchers involved in his study understand the difference between the ubiquitous and non-specific symptom/condition of chronic fatigue and the distinct disease ME; NIH staffers frequently use them interchangeably. Surely, it would be unacceptable at NIH if its researchers studying lung cancer kept referring to the disease as chronic cough, but Nath snapped at Ms. Holderman’s entirely reasonable request saying that he “can’t police anybody.” Ms. Holderman replied that she wasn’t asking for policing but for educating.

Ms. Holderman also asked for assurance that the intramural study will be using the experts’ criteria, the CCC and the ME:ICC. Nath, audibly annoyed at Ms. Holderman’s valid concern about patient recruitment, claimed emphatically that he has made “absolutely certain, beyond any element of doubt, that [NIH was] recruiting the right patients for the study.”

It is a bit rich, but typical for Nath, to curtly dismiss advocates’ cohort concerns given that he allowed the inclusion in the patient cohort of a high percentage (about a quarter) of individuals who spontaneously recovered, i.e., whose ME diagnosis is highly questionable, as well as the inclusion in the control group of individuals with health issues that have substantial symptom overlap with ME, such as orthostatic intolerance (Supplementary Results, page 9, see screenshot below), Psoriasis (Supplementary Results, page 21, see screenshot below), a chronic systemic immune-mediated (autoimmune) disease without a cure (notwithstanding the authors’ attempt to make it look as though the control with Psoriasis recovered), Chronic Lyme Disease (Supplementary Results, page 21, see screenshot below) as well as blood relatives of patients with ME, a disease with at least an infectious component.

Nath’s ill-tempered petulance is particularly hypocritical in light of the bait-and-switch “commitments” that were made by NIH but not kept with respect to the study. For example, after promising the community in 2016 that every patient participant would satisfy the CCC, only about half of the patients in the intramural study did.

Nath’s study also did not objectively confirm that ME patients in the study suffered from PEM (which would have required a two-day CPET), again contrary to what NIH had committed to in 2016. Nevertheless, Nath claims that “the patient population was very clean” with “the best patients” when, it truth, the ME cohort was messy. It is almost as if words have no meaning at NIH, both linguistically and ethically.

Ms. Holderman put it well when she recently tweeted the following:

During the May 28, 2024 NIH ME/CFS Advocacy call, Nath again escalated his anti-advocacy rhetoric. He started out by saying, “We made significant progress so far studying ME/CFS, but I think further progress is only possible if we have a true partnership with the patients.” He continued saying that he sees this as key for further NIH research on ME. He then made it very clear that ongoing criticism of the NIH study by patients and advocates will have consequences for future ME research:

“But if you’re hypercritical of the very people and the researchers who are trying to help you, then we do get demoralized, and you tear us apart, and then it becomes very difficult to achieve the goals that we set out to achieve.”

(NIH assured us on the day of the event that a recording and transcript of it will be posted to the NIH website “soon,” but the agency has still not released them or any statement as to what is causing the delay.)

Although Nath used euphemisms (“very difficult to achieve the goals that we set out to achieve”), this was an attempt, by a high-ranking NIH scientist and bureaucrat, to intimidate and silence a patient group that has been belittled, mocked, neglected and harmed for decades. It is abusive and unbecoming of a civil servant of Nath’s stature in the agency’s hierarchy to denigrate and guilt-trip ME advocates and promise consequences in case of sustained criticism. Nath is exploiting the tremendous power differential between NIH and patients.

One has to ask: A scientist who was involved in early AIDS research and, therefore, witnessed the AIDS community’s Act Up advocacy is trying to vilify ME advocacy as too much?! It is absurd. What is different to Nath about ME patients that makes him deem them not entitled to fight for their health even with much less aggressive advocacy methods than AIDS patients did due to the severe health limitations ME imposes? The fact that they are not mostly men? This is not the first time that attempts have been made to shame ME advocates and put them on the defensive with demands for “inside voices,” but it is time that the appropriate authorities take a look at Nath’s tactics.

Advocates had laid out the case against Walitt in 2016 in no uncertain terms, but Nath has been so disgruntled by being forced to be involved with ME research in the first place that he hardly could have cared less. In fact, Nath clearly feels that he owes Walitt for getting him out from under the weight of the ME study. Nath frequently goes out of his way with over-the-top praise for Walitt, alleging that the intramural ME study would not have been possible without Walitt, a preposterous assertion. If Walitt were indeed holding NIH together, then it really would be no wonder that the reputation of the agency is crumbling.

Nobody can accuse advocates of not trying, every way physically possible, to get Nath and NIH to take seriously their manifestly valid concerns with respect to this study, but Nath has been brushing them off time and time again. He has no plausible deniability. Nath had a number of off-ramps to keep harm from coming to ME patients, but he chose none of them. Instead, he proceeded to let Walitt run the intramural study. The fact that Walitt volunteered should have been a red flag for Nath, and certainly when Walitt included the EEfRT testing in the study design, Nath should have stepped in. Not even Walitt’s invitaton of Dr. Edward Shorter, who has been openly expressing his loathing for ME patients, in order to indoctrinate other NIH researchers with biopsychosocial brainwashing before the study even started gave Nath pause. Nath approved the inclusion of the EEfRT testing, the misinterpreted and misrepresented EEfRT results, and the framing of ME exactly as Wessely has done: as a condition characterized by a false sense of effort followed by deconditioning.

The community has been subject to major-league gaslighting as a result of NIH’s riding out of the huge protest against Walitt’s involvement with the study instead of acting on it and replacing him. It is breathtaking that Nath has allowed somebody with Walitt’s odious views to capture ME at NIH by designing and running the first intramural ME study in decades and becoming principal investigator of other NIH intramual ME studies. Instead of protecting ME patients against that bias, Nath has enabled Walitt.

Short of giving a press conference announcing that ME patients are malingerers, NIH could not have done more harm than it did with this study, but when advocates protest the outcomes that they had been trying to prevent, Nath farcically takes the criticism personally and centers himself without addressing or even considering the issues raised in earnest. How dare advocates point out the dangerous consequences of his paper, which he either never considered or found desirable. The level of hubris is astounding.

Any alleged ignorance of the false EEfRT findings on the part of Nath is betrayed by his defensiveness and unequivocal commending of Walitt. Nath feels boxed in, and lashing out—not against Collins or Walitt but against advocates—is all he can think of as a response. Taking responsibility and changing course has apparently not crossed his mind.

Aren’t scientists supposed to be curious? The firestorms relating to Walitt and Effort Preference would have given any inquisitive, reasonable, non-defensive, and open-minded researcher pause and a chance to realize that he or she has missed something important, but not Nath; he went straight to recycling the harmful patients-are-difficult trope.

Nath’s decrying of, and discomfort with, advocates’ “pick[ing] apart every single word” (NIH Symposium at 22:18) is another shameless push-back against accountability of tax-payer-funded civil servants. There would be no need to be afraid of their words being scrutinized if Nath and some of his colleagues did not harbor the ugly prejudices that they do and if their research was not fairly obviously inserting contrived non-medical terms and concepts into the literature without validation and on an extremely unstable experimental foundation. It is telling that, at the NIH Symposium, real-time questions from the virtual audience (something that is technologically easy to do in 2024) were not allowed. Instead, online attendees had to submit their questions in advance, allowing the NIH investigators to spin their answers in advance or to choose not to answer them at all.

Nath’s demands of accolades. Nath has more than once urged patients to thank the NIH researchers involved in the intramural study, including during the recent NIH Symposium on the intramural study (at 22:18). He did this despite being acutely aware that there has been a tremendous amount of compelling criticism of the study. Nath seems to feel deeply offended by any scrutiny of the research he is responsible for and cannot fathom what could possibly give rise to any condemnation of his study or the way that NIH has handled ME over the decades.

Nath, as a loyal company man, is trying to deny, all evidence to the contrary, the deeply entrenched and well-established institutional bias against ME patients that pervades NIH and that was clearly a major factor in the outcome of the intramural study by acting as though the decades-long neglect by and harm from NIH has not happened, is not ongoing, and does not matter. Promoting that revisionist history alone is harmful, something that Nath is intellectually perfectly capable of seeing but refuses to acknowledge.

Astonishingly, Nath admonished Ms. Holderman on the May 28, 2024 NIH Advocacy Call and demanded:

”You should be more appreciative instead of critical.”

Ms. Holderman’s offense? She questioned the use of three vastly different diagnostic criteria for patient-selection purposes in the intramural study, in particular the strongly opposed IOM definition.

As I explained throughout this four-part article, there were serious cohort issues, which Nath continues to deny. He rationalized the investigators’ choice of diagnostic criteria in response to Ms. Holderman by asserting that there are no good objective diagnostic criteria and that all ME symptoms are subjective. So, the principal investigator of the intramural ME study who just received an award for his involvement with this very study is unfamiliar with the well-established objective symptoms in ME and the ME:ICC, the gold standard for use in research among all the ME definitions? Nath did not even try to justify the use of three different criteria. Surely, NIH would have been able to find 17 patients who satisfied the same diagnostic criteria.

Nath’s concealing of the effort testing from the ME community. Whenever Nath has presented on the study details to the patient community over the years, he scrupulously avoided any mention of Effort Preference or the EEfRT, which indicates that he was acutely aware of the harmful nature of the effort “inquiry,” knew how it would be perceived by the community, and was hiding that prejudicial ball from patients and advocates as long as possible. At the same time, he has not hesitated to now broadcast the Effort Preference claim to the media, and, of course, it is front and center in the paper. This selective and strategic concealing of the effort testing and claim in presentations to ME advocates and patients  shows that Nath has, of course, not been some obtuse bystander who did not realize what Walitt was up to.

To this day, when Nath and/or Walitt present on the intramural ME study to the ME and Long COVID communities, they carefully conceal the fact that they tested for effort in the ME study. Neither ever mentions their Effort Preference claim in those presentations. Below is the slide that Walitt used on the May 6, 2024 CDC ME/CFS Stakeholder Engagement and Communication call, where he and Nath were guest speakers and which turned out to be mostly about NIH’s Long COVID research. As you can see, the effort testing is not mentioned. Nevertheless, Walitt will use the same testing NIH used in the ME study in ongoing Long COVID research. In fact, Nath said during the CDC call that the Long COVID research will be “based on what we did with ME. We are doing very similar kinds of studies in Long COVID so we can compare the two.” Long COVID patients are getting a preview of what is in store for them at NIH.

Nath’s cognitive dissonance. It is hard to imagine that anything ME advocates have to say—no matter how morally, scientifically, or logically compelling—could get through Nath’s defenses. He is committed to refusing seeing himself and this study in the context of the river of malfeasance, neglect, and abuse of NIH et al., or what Nath calls patient “conspiracy theories.” At his level of cognitive dissonance, he is unreachable and unwilling to acknowledge his part in this particularly destructive era of ME history and will just dismiss as unwarranted and invalid any patient input other than unqualified praise. His sense of self-preservation and need to protect his immaculate self-image are obviously stronger than his sense of duty and his sense of responsibility vis-a-vis patients who have waited half a lifetime for any help from NIH.

The only path forward between the ME community and NIH. There can be no healing of the NIH-patient relationship without removing all adherents of the biopsychhosocial school from future ME studies at NIH, a retraction of the intramural ME study, a Congressional investigation into the institutional and decades-long NIH malfeasance (advocates want names!), and major restorative funding commensurate with the burden of ME—at the very least at the same level as Multiple Sclerosis is funded, which for 2025 is estimated to be $116 million per year—and retroactive for 40 years. ME patients have every right and compelling reasons to demand accountability.

At the moment, NIH is moving in the opposite direction: both Koroshetz and Nath continue—after 40 years of this very neglect by NIH—to be unequivocal and unabashed about their expectation that ME patients be satisfied with any crumbs that may or may not materialize as the result of Long COVID research. Just one example of ME’s bottom-of-the-list status at NIH is the recent intramural deep phenotyping Long COVID study (principal investigator and senior author: Nath) for which recruitment began in 2020. The paper was published in May of 2023, less than three years later. That is in stark contrast to the more than eight years it took for NIH’s intramural ME study. If it is left up to NIH, it will never be ME’s turn.

Nath’s legacy. I predict that his fateful decision to put Walitt in charge of the intramural ME study will become Nath’s legacy. The vocal protests of the study are here to stay until the paper is retracted and those responsible held to account. Advocates will keep fighting this perversion of science and decency as long as it takes and remind everybody of what has happened under Nath’s supervision. They will not be bullied into silence by Nath or anybody else at NIH, and any further such attempts will only strengthen their resolve to expose this study and get it retracted. NIH pushed it too far with its unsupported and destructive Effort Preference claim, and somebody will have to atone for it. Nath chose harm for ME patients. There is room for him to redeem himself by blowing the whistle on this study. The decision is his, but I am not holding my breath.

Conclusion

By NIH’s own admission, the intramural ME study has been first and foremost a delivery vehicle for the brand-new Effort Preference term and concept in ME, which, in essence, asserts, instead of being objectively physically limited, that ME patients falsely believe, as the result of a dysfunctional effort perception, that they are unable to exert themselves past their limits, resulting in deconditioning and functional disability. NIH had obviously decided that the fatigue label, which it has used to falsely describe ME for decades, was no longer damaging enough.

NIH invented Effort Preference as defining of ME, which is not supported by the data and which is deeply and glaringly derogatory and severely harmful. The agency then contaminated everything else in the intramural paper by relating it all to the new Effort Preference concept. By doing so, NIH formalized Wessely’s theory on ME as an issue of false perception of effort and fatigue. This is about as hostile to the ME community as one can imagine. If NIH had had even just neutral intentions, the authors would have presented the immunological findings as the primary findings instead of altered Effort Preference

This constitutes a defamatory assault on ME patients. Since the publication of the paper, NIH has been flailing, trying to put a benign spin on the effort claim with a disingenuous, contrived re-framing that does not stand up to scrutiny. Because the alleged Effort Preference findings are tied in with the other findings of the study, the entire paper is tainted and has to be retracted. We all know that the peer-review process is broken, and this paper is an effective illustration of that.

The issues laid out in this four-part series are extremely serious. Whether or not they rise to the level of research misconduct is yet to be determined. The sheer number and the nature and severity of the issues combined with the well-documented ME agenda on the part of the agency and several of the investigators in this study suggest at the very least recklessness—that much incompetence at NIH would be shocking but not surprising in light of the absence of accountability at the agency—if not knowledge or, more likely, intent.

Fortuitously, Congress is primed to take this on because NIH has been under tremendous and well-deserved scrutiny lately as the result of its habitual and systematic FOIA violations and its failure to advance Long COVID research, etc. NIH is certainly not as untouchable anymore as it had been for decades as Congress is breathing down its neck, and that will work in favor of the ME community as it continues to take on this study. Maybe what NIH had done to the ME community will be the last straw that will lead to meaningful NIH reform.

Further effort research in ME is ongoing at NIH. The agency is determined to reduce ME to a condition of misunderstood capacity resulting in deconditioning. The harm done as a result of reframing ME as chronic fatigue in 1988 will pale in comparison to what lies ahead in the wake of Effort Preference.

Call to Action

I urge readers to file complaints by sharing my four-part analysis with the following authorities:

1. your U.S. Senators and Representatives
2. the NIH Director, Dr. Monica Bertagnolli:
   • monica.bertagnolli@nih.gov
3. the Director of Research Integrity and the Agency Intramural Research Integrity Officer (AIRIO), Dr. Kathy Partin (https://oir.nih.gov/sourcebook/ethical-conduct/research-misconduct):
   •  kathryn.partin@nih.gov
4. the HHS Office of the Inspector General (OIG). OIG complaints can be filed in a variety of ways as follows:
   • online: https://oig.hhs.gov/fraud/report-fraud/
   • by U.S. mail:
     • U.S. Department of Health and Human Services
       Office of Inspector General
       ATTN: OIG HOTLINE OPERATIONS
       P.O. Box 23489
       Washington, DC 20026
   • by fax: (800) 223-8164

with requests to:

1. investigate the study
   1. with respect to potential gross misconduct and potential research misconduct, including, but not limited to, falsification of data, i.e., manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record
   2. constituting a significant departure from accepted practices of the relevant research community and committed intentionally, knowingly, or recklessly,
2. discipline any individuals involved in the foregoing improprieties, if any, and
3. retract the NIH intramural study.

As we cannot know all the individuals who were involved with the EEfRT testing, the complaints should be made against:

1. Dr. Avindra Nath as principal investigator of the study and
2. any other individuals at NIH involved in any the EEfRT testing in any way (including, but not limited to, the design, administration, and interpretation of the EEfRT testing), including, but not limited to, Dr. Brian Walitt and Dr. Nicholas Madian.

Please feel free to use the following summary of some of the potential misconduct, the inclusion of which in your correspondence may expedite the authorities’ determination to investigate the matter. Please make it clear that this is a non-exhaustive list of potential misconduct:

1. The inclusion in the paper of a graph, Figure 3a, in order to support the Effort Preference claim, that was the result of statistical manipulation resulting in a completely misleading presentation of the data, which, when graphed, present a picture that contradicts Figure 3a
2. The claim that ME patients chose fewer hard tasks than controls “at the start of and through the [EEfRT]” with Figure 3a claiming that patients chose fewer hard tasks in every single trial
   1. During the May 2, 2024 NIH Symposium on the study, Dr. Madian stated, “We did again see a difference at baseline, which persisted throughout the task, indicating differences in effort discounting.”
   2. Out of the first four trials, ME patients and controls chose the exact same number of hard tasks per participant. For the very first trial, arguably “the start” of the EEfRT, patients chose twice as many hard trials as controls, even though the patient cohort consisted of one fewer individual than the control cohort.
   3. For 34% of the trials, ME patients chose hard tasks at a higher rate than controls. For another 2% of trials, both groups chose the same percentage of hard tasks. During an additional 14% of tasks, both groups’ hard-task choices were nearly identical, and the difference was, therefore, not statistically significant.
3. The inclusion of randomly assigned tasks (hard versus easy) in the analysis of hard-task choices despite no choice having been made in those cases, which occurred substantially more often in the case of patients than controls and with a substantially higher percentage of the randomly assigned tasks being easy tasks in the case of patients compared to controls
4. The omission of an analysis of the obvious impact of patients using a game optimization strategy and the conclusory claim (without discussion) that there was no resulting group difference in probability sensitivity despite the fact that there was a significant difference between groups for 12% and 50% probability trials but not for 88% probability trials, negating any basis for the Effort Preference claim
5. The use of an improper metric, number/ratio/probability of hard-task-trial choices, in support of the Effort Preference claim, as opposed to the correct metric, the average rewards earned by both groups, for which there was no significant difference between the two groups (less than 1%), negating any basis for the Effort Preference claim
6. The failure to address or even acknowledge significant confounding factors and to attempt to control for them or at least minimize their impact, contrary to other EEfRT studies, for example:
   1. the failure to exclude from the EEfRT patients taking benzodiazepines
   2. the failure to control for patients’ motoric or other physical impairment to complete hard tasks by calibrating the maximum required button-press rates to individual physical ability despite numerous prior EEfRT studies emphasizing the need to do so
   3. the failure, contrary to what prior EEfRT studies have done, to exclude five patients who were physically unable to complete hard tasks at a reasonable rate or at all (the combined hard-task completion for those five patients was less than 16%) leading to a significant group difference in the ability to complete hard tasks (96.43% for controls versus 67.07% for patients), invalidating the EEfRT data and analysis
      • During the May 2, 2024 NIH Symposium of the study, Dr. Madian stated, “What the [original EEfRT] paper describes is that the EEfRT was designed so that the sample of patients used within that original study could consistently complete the task. This does not mean that everyone who takes the task must be able to complete the task without issue for the administration or data to be valid or interpretable. It seems that the creators wanted to ensure that in general as many people as possible would be able to complete the task but without compromising the task’s ability to challenge participants. Furthermore, I think, it bears mentioning that although our ME participants did not complete the task at the same 96-100% rate as the participants in the original study or at the same rate as our healthy controls, they still completed the task a large majority of the time. To wrap things up, to answer the question, consistently completing the task is not a requirement for a valid EEfRT test administration, and by all accounts we believe our data is valid and is, thus, interpretable as a measure of impaired effort discounting.” This is a misrepresentation of the what the original EEfRT study found (required task completion by “all subjects”) and what subsequent EEfRT studies have stressed. Furthermore, it is untrue that patients “completed the task a large majority of the time.”
7. The inappropriate use of a test (the EEfRT), that was designed for and has been exclusively used for mental-health issues (or in healthy individuals), in order to support a novel and newly introduced term and concept, Effort Preference, in a physical disease
8. The failure to discuss the validity of the use of the EEfRT in an unprecented way, i.e., to measure alleged disrupted effort discounting as opposed to the established use of EEfRT results as an assessment of effort-based, reward-based motivation
9. The failure to identify any limitations of the EEfRT testing contrary to what other EEfRT studies have invariably done
10. The failure to exclude the data of four “spontaneously recovered” ME patients (about a quarter of the patient cohort), a recovery rate well above of what has been found by credible researchers, indicating that at least some of those patients were misdiagnosed
11. The over-generalization of the unsupported Effort Preference claim beyond the expending of effort for small gambling rewards, i.e., for any effort exertion by ME patients
12. The over-generalization of the unsupported Effort Preference claim to millions of ME patients worldwide based on the one-time EEfRT performance of 15 ME patients, some of whom seem to have been misdiagnosed
13. The inclusion of data from healthy controls with diseases that have substantial symptom overlap with ME (orthostatic issues in high numbers, Chronic Lyme Disease, and Psoriasis) as well as the inclusions of two blood relatives (siblings) of ME patients in the study despite the fact that there seems to be at least an infectious component to ME
14. The choice of a new and exceedingly prejudicial label for a patient community that has suffered grave harm from decades of misrepresentation of the disease nature and from sustained and relentless defamation, including by NIH
15. The use of three vastly different criteria (two of which are overly broad) for patient selection, including one set of criteria, the IOM definition, that is not a research definition, which likely resulted in including individuals in the patient group who were not ME patients
16. The claim to have established the ME phenotype based on an exploratory, hypothesis-generating study of a cohort of only 17 patients, with many tests run only on even smaller sub-subsets of patients
17. The misrepresentation of the nature of ME by reducing it to mere fatigue, exercise intolerance, malaise, and cognitive complaints, which is a non-specific description that does not capture ME, a multi-system disease with a variety of other disabling symptoms
18. The assigning of a researcher to design the study and run its day-to-day activities, Dr. Brian Walitt, who is on record with his unscientific views of ME, for example, that it is merely a normal way of experiencing life and not a medical entity
19. The hostility, derision, and unprofessional conduct by the principal investigator Dr. Avindra Nath, a high-level civil servant, toward the ME community:
    1. his persistent demands of unqualified praise from the ME community,
    2. his veiled threats as well as his overt intimidation with respect to future ME research in an attempt to silence criticism by advocates of the intramural study and NIH’s research and conduct, causing pain and suffering to ME patients,
    3. his presenting himself as a victim of ME advocates, gravely sick patients, causing reputational harm to the ME and ME advocacy community, and
    4. his relentless stressing that he and the other researchers in the study have allegedly been forced to donate their time and work without compensation for ME patients

Many thanks to all advocates, patients, caregivers, and concerned stakeholders who are taking part in this Call to Action. I realize that what I have described is outrageous and might invoke justifiably strong emotions, but keeping our correspondence and meetings (some of which are already underway) professional and polite is most likely to produce results.

***

I would like to thank Eileen Holderman, Ella Peregrine, Carrie Patten, and Ed Burmeister for their invaluable feedback, contributions, and support. I am solely responsible for any inaccuracies or mistakes in the analysis.

I have no conflicts of interest and, in particular, am not compensated by any government agencies, ME non-profits or experts, or other patients.

Open Access: In my four-part series on the Effort Preference claim, I shared quotes, data, images from the paper “Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome” and its attachments under the Creative Commons license, a copy of which can be found here. I indicated when and how I re-analyzed the data.