Peter White

Peter Denton White is a British psychiatrist and a prominent researcher in the field of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). White was an honorary consultant liaison psychiatrist at St Bartholomew's hospital and the co-lead of the East London chronic fatigue syndrome service until he retired from these positions in 2016.His research in ME/CFS focused on fatigue symptoms following Epstein Barr virus infection, subgrouping and the role of cytokines in ME/CFS and the development of graded exercise therapy. As lead author of the controversial PACE trial, White was criticized for misrepresenting the study’s findings in favor of cognitive behavioral therapy and graded exercise therapy.

Biography
Peter Denton White qualified in medicine at St Bartholomew’s Hospital Medical College. He was trained in general medicine in Southampton and received his psychiatric training at the Maudsley and St Bartholomew’s Hospitals. He became Professor of Psychological Medicine at Barts and the London Medical School, Queen Mary University of London and was a consultant liaison psychiatrist and co-lead of the chronic fatigue syndrome service at St Bartholomew’s hospital, until he retired from these positions in 2016.

White was one of the authors of the British diagnostic criteria for CFS, often referred to as the Oxford definition. In 2002 White was one of the members of the Chief Medical Officer’s Working Group for ME/CFS, a position from which he resigned due to disagreements about the final report.

White currently is a trustee of the Voluntary Hospital of St Bartholomew's and a member of the Independent Medical Experts Group, which advises the UK Ministry of Defence regarding its Armed Forces Compensation Scheme. He also provides paid consultancy to re‐ insurance companies.

Fatigue following the Epstein Barr Virus (EBV)
In a large longitudinal study, White and colleagues followed up on 108 persons with Epstein Barr Virus (EBV-) infection, 83 patients with glandular not caused by EBV and 54 subjects with an ordinary upper respiratory tract infection (URTI). These patients were followed up for more than six months to assess symptoms and disability. The results suggested that a distinct fatigue syndrome existed after glandular fever whose constituent symptoms were reliable over time. The prevalence of CFS according to the Fukuda definition was 10%, six months after EBV-infection compared to 0% following an ordinary URTI. No psychiatric disorder was significantly more prevalent six months following EBV-infection than before. According to White et al. “The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular.”

Using data from the General Practice Research Database (GPRD), White and colleagues reported that significantly more fatigue symptoms were reported in the months following EBV-infection compared to tonsillitis and influenza. White is also a member of The International Collaborative on Fatigue Following Infection (COFFI) which has been established to study post-infection fatigue and related symptoms by sharing data and samples from cohorts around the world.

Graded exercise therapy (GET)
Peter White helped develop graded exercise therapy (GET) for CFS, on the basis that the illness is maintained by both the avoidance of activity and deconditioning. In of his studies CFS patients were compared to sedentary controls. While both were equally unfit, CFS patients had reduced exercise capacity and perceived greater effort during exercise than sedentary controls.

With GET patients are instructed to gradually increase their level of physical activity. Under the guidance of a trained physical therapist, patients are instructed to find a baseline of physical activity they can easily manage, even on bad days. From there, the amount of exercise is increased time-contingently with the goal of reaching 30 minutes five times a week. When patients reach their goals, the intensity of exercise can be increased for example by going from walking to running or swimming.

According to White, patients can improve and even recover from CFS by following GET. He has argued that “patients can be released from their self-perpetuating cycle of inactivity if the impairments that occur due to inactivity and their physiological deconditioning can be reversed. This can occur if they are willing to gradually exceed their perceived energy limits, and recondition their bodies through GET.”

White has conducted three randomized trials that assessed the effectiveness of GET. All claimed that CFS patients significantly improved in the GET-group, although the results have been challenged by others. A review by Vink & Vink-Niese indicated that patients rarely improve on objective outcomes following GET. White has acknowledged that “GET does not work by improving physical fitness” but argued that it may work by improving exercise tolerance or reducing fear avoidance.

The use of GET has been controversial in the ME/CFS community. In several surveys, patients indicated to have been harmed by this treatment. White has said that reports of harm are merely examples of GET being wrongly applied, for example when patients are told to go to the gym to exercise without any guidance - an explanation that has been contested. White has acknowledged however that “It is an apparent paradox that graded exercise programmes are prescribed for patients with CFS/ME, when post-exertional malaise is a feature, which requires explanation.”

Risk factors and prognosis
Using data from the 1958 British birth cohort White was able to study premorbid risk factors for (self-reported) CFS/ME. The study could not confirm a connection with activity levels in child- or adulthood. Female gender, premorbid psychopathology, childhood gastrointestinal symptoms and parental reports of many colds increased the risk of self-reported CFS/ME in later life. There was also an association with parental physical abuse, although this factor was assessed retrospectively.

Using data from the General Practice Research Database (GRDP), White and colleagues were able to report that viral infections were a risk marker for CFS, while gastroenteritis put persons at greater risk for irritable bowel syndrome.

Using the GRDP, White estimated the incidence of CFS to be 14.8 per 100,000 people. The data indicated that the incidence of CFS had remained relatively constant during the period 2001-2013, even decreasing a little over time. White and colleagues also reported that CFS-patients had a 50% increased GP consultation rate in the 10 years before their CFS diagnosis in the GRDP, compared to controls. Healthcare consumption peaked in the year of CFS/ME diagnosis but quickly reached levels similar to the period before diagnosis.

Biomedical research: cytokines
In one of his first papers featuring CFS, White speculated that the condition may be the result of activated cytokines such as Interleukin 1. He subsequently tested the activation of cytokines in CFS patients before and after performing an exercise test. In a 2015 review, however, White and colleagues reported that studies on cytokines in CFS are often of poor quality and have conflicting results. According to the authors, the only consistent finding has been an increase in transforming growth factor-beta (TGF-β). A subsequent study by White’s research group showed that TGF-β was the only cytokine significantly increased in CFS patients compared to controls, but that this was considered “a spurious finding due to variation between different assay batches.” According to the authors, the results suggest that “elevated circulating cytokines are not important in the pathophysiology of CFS” although a role for local release of cytokines in the central nervous system (CNS) was not ruled out.

Subgrouping
White has argued that CFS is a heterogeneous label representing more than one separate condition and that this might explain the lack of replication in the field. “If CFS is found to be more than one separate condition", he wrote, “this could explain why no replicated causes have been found associated with the illness, since an association found only in one subgroup would be diluted, and risk being found non‐significant, by mixing the subgroup with others.”

White was able to perform subgroup analysis on the data collected during two large epidemiological studies by the Centers for Disease Control and Prevention in the United States. Principal components analysis was conducted on selected CFS patients, patients with idiopathic chronic fatigue and healthy controls from the Wichita, Kansas study. The analysis indicated 6 different classes which were mostly based on factors such as obesity, depression, and apnea. Similar groups were found in the analysis of data from the CDC’s prevalence study in Georgia. According to the authors, this replication supported “the broadening of the concept of CFS to include patients with fewer symptoms but similar disability.” White has recommended that NICE guidelines for the diagnosis of CFS as the most useful as it requires only one additional symptom beyond post‐exertional fatigue.

White has however been critical of proposals to lump several functional somatic syndromes (FSS) - which in his view includes ME/CFS - into one diagnostic entity. He has argued that there is little overlap between conditions such as fibromyalgia and irritable bowel syndrome, that treatments and risk factors between FSS may differ and that “historically, more progress has been made through splitting illnesses rather than lumping them together.” According to White “A general functional somatic syndrome can be consistent only with psychogenesis, since it is difficult to conceive of a pathophysiological mechanism that would be common to all functional somatic syndromes.”  As an alternative White proposes to be “over‐inclusive regarding the diagnosis as a first step, while subdividing the condition into likely subgroups as a means of finding valid and reliable associations with potential causes”

Central Sensitization
While White has originally emphasized the role of deconditioning in the pathology of CFS, in recent years he has highlighted the potential role of central sensitization, a suspected hypersensitivity of the central nervous system. He has argued that central sensitization may form a common link between functional somatic syndromes, whereas precipitating events such as environmental exposures could mark the development of specific syndromes or their sub-phenotypes. White has also emphasized the role of interoception and abnormal perception of effort in CFS.

PACE trial
Peter White was the lead investigator of the PACE trial, a 5 million pound study that investigated the effectiveness of cognitive behavioral therapy (CBT), graded exercise therapy (GET) and adaptive pacing therapy (APT) in a sample of more than 600 CFS patients. While the reported findings indicated that CBT and GET were effective treatments for CFS, the authors have been criticized for misrepresenting the trials’ results. The PACE authors deviated from the methods specified in their protocol, without explaining these changes in full in their publications or how the changes impacted the reported findings. Following inconsistencies in the economic analysis of the PACE trial, health psychologist James Coyne filed a request to the journal PLOS ONE to access the data of the trial, a request that was dismissed as vexatious by Kings College London. PLOS ONE has since issued an expression of concern about the publication in question.

The PACE authors have refused to share the trial's data for independent reanalysis due to concerns that “patients might be personally identified by releasing their data.” Peter White has criticized the "All Trials campaign" as it encourages authors to share their datasets publicly. During a 2015 first tribunal hearing on the release of the PACE trial data, Professor Ross Anderson defended the PACE authors’ decision by making “wild speculations” about “young men, borderline sociopathic or psychopathic” being attached to criticism of the PACE trial. The tribunal considered these claims to be unfounded and ordered the release of some of the anonymized data of the trial. An independent reanalysis showed that the PACE authors had inflated improvement and recovery rates threefold. An open letter signed by more than 100 prominent ME/CFS experts including researchers, clinicians, and MPs has called for “an independent re-analysis of the individual-level trial data, with appropriate sensitivity analyses. According to White et al. criticism of the PACE trial is based on “misunderstandings and misrepresentations”. In an article in the Guardian, White wrote that ‘If my team’s research on ME is rejected, the patients will suffer.”

An adverse effect of the label ME
In one of their studies using the GPRD, White and colleagues reported that the prognosis of patients diagnosed with ME was worse than those diagnosed with CFS or post-viral fatigue syndrome. The authors considered it unlikely that there was a difference in the underlying condition which the GP’s could accurately differentiate. They speculated that the poorer prognosis of ME was due to the label itself. “It is possible”, the authors wrote, “that the label ME with its suggestion of an untreatable pathological process may somehow render the patient less able to combat their symptoms and disability than other labels.”

Resigning from the CMO working group
White was one of the members of the Chief Medical Officer’s Working Group for ME/CFS, a position from which he resigned due to disagreements about the final report. White and other members who resigned found that the report played down the psychological and social aspects of the condition and concentrates on a medical model. In an Editorial, White explained that criticism of the report included the “dangers of both over-medicalisation of chronic fatigue and the iatrogenic damage consequent upon that.” White also disagreed with the inclusion of pacing as a recommended treatment advice, writing that “the theoretical risk of pacing is that the patient remains trapped by their symptoms in the envelope of ill health.”

Comments on 2007 NICE guideline
During the development of the 2007 guidelines form the National Institute for Health and Care Excellence (NICE), several controversial comments were made to the draft version of the report, by St Bartholomew’s Hospital Chronic Fatigue Services, which at the time was headed by Peter White. The comments criticized the provision of equipment and adaptations (for example, a wheelchair,blue badge or stairlift) to allow individuals to improve their independence. St Bartholomew’s provided the following feedback: “Where is the warning about dependence being encouraged and expectation of recovery being damaged by the message that is given in this intervention? We are in no doubt that it is a powerful message for a therapist of any sort to provide such aids. Our view is that such aids should only be considered by a multi-disciplinary therapeutic team as a whole, and usually in the context of providing a temporary means for a patient to increase their activity levels.” Regarding multiple chemical sensitivites (MCS), Bartholomew’s commented that  “MCS is a potentially remediable condition through a graded exposure programme on the basis that the underlying pathophysiology is a conditioned response. It should not be considered as a part of CFS/ME.”

WHO classification
White has repeatedly stated that there are multiple ways of classifying CFS using the World Health Organization's International Classification of Diseases, version 10 (ICD-10). He has claimed for example that “chronic fatigue syndrome may be classified as myalgic encephalomyelitis (ME) within the neurology chapter (G93.3) of ICD-10, or as neurasthenia, a psychiatric disorder (F 48.0).” The WHO however classifies ME, CFS and post-viral fatigue syndrome (PVFS) under code G93.3 in Chapter VI Diseases of the nervous system of ICD-10, and has made clear that it “is not permitted for the same condition to be classified to more than one rubric”. ICD-10 explicitly excludes code G93.3 (PVFS, ME and CFS) from the neurasthenia diagnosis F48.0.

White has also stated incorrectly that CFS can be classified under “R53.82 Chronic fatigue, unspecified, which includes chronic fatigue syndrome NOS.” There is however no such code in the ICD, only In the U.S.'s clinical modification, ICD-10-CM. White has also written that "Fink's concept of body distress syndrome” was recently incorporated into ICD‐11, which is incorrect. For the core ICD-11, WHO has approved the differently conceptualized, "Bodily distress disorder (BDD) which is distinct from Fink’s concept.

In a lecture for the re-insurance company Swiss RE, White gave the advice to diagnose patients with the label CFS rather than ME, as this makes it easier to use a mental health exclusion in insurance policies. He argued  that “a diagnosis of Myalgic Encephalomyelitis or ME (a term often used colloquially instead of CFS) is considered a neurological condition according to the arrangement of the International Classification of Diseases (ICD) diagnostic codes whereas CFS can alternatively be defined as neurasthenia which is in the mental health chapter of ICD10.”

Conflict of interests
Peter White has performed paid and unpaid work for the United Kingdom's Department of Work and Pensions, which is the department that is responsible for administering and arranging the assessment of sickness and disability health payments, including the controversial Employment Support Allowance (ESA) and Personal Independence Payments (PIP) for people of working age. White also provides paid consultancy to re‐ insurance companies.

White did not disclose his financial conflicts of interest to the participants of the PACE Trial, of which he was the lead investigator. According to Journalist David Tuller, The PACE authors “promised in their protocol to adhere to this foundational human rights document, among other ethical codes. Despite this promise, they did not tell prospective participants about their financial and consulting links with insurance companies, including those in the disability sector. That ethical breach raises serious concerns about whether the “informed consent” they obtained from all 641 of their trial participants was truly ‘informed,’ and therefore legitimate.”

Peter White was a director of OneHealth (Company number 04364122) from 2002 to 2010. The memorandum of association states that the purpose is to promote the biopsychosocial model of illness. From 1999 to the present, White has been a director of Added Value Advisory Services (Company number 03764154), a company that focuses on “management consultancy activities other than financial management.”  Since November 2018 White is also director of PDW Medical Limited, a company that focuses on specialists medical practice activities.

Notable studies and articles related to ME/CFS

 * 2003, Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution (Full Text)
 * 2004, Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome: A Pilot Study
 * 2013: The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial
 * 2016, Complementary and alternative healthcare use by participants in the PACE trial of treatments for chronic fatigue syndrome
 * 2016, A UK based review of recommendations regarding the management of chronic fatigue syndrome
 * 2017, Response to: "Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments?" (Abstract)
 * 2017, Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001–2013: a Clinical Practice Research Datalink study (Full Text)
 * 2018, The International Collaborative on Fatigue Following Infection (COFFI) (Full text)

Talks & interviews

 * What is CFS, and what is ME? Bergen, October 20 2009
 * What causes CFS/ME, and does this determine treatment? Bergen, October 20 2009
 * Treatments for chronic fatigue syndrome. Bergen, 20 October 2009
 * Royal Society of Medicine, 28 April 2008 (Transcript)
 * BBC You & Yours transcript, 5 November 2007

Books

 * 2005, Biopsychosocial medicine - An integrated approach to understanding illness

Online presence/List of Publications

 * PubMed - Peter D White
 * Publications Peter White

Directorships and Shareholdings
Peter Denton White is a director and has 2 total appointments. He is a director of OneHealth (Company number 04364122) from 2002 to 2010. The memorandum of association states that the purpose is to promote the biopsychosocial model of illness. He is also a director of Added Value Advisory Services (Company number 03764154) from 1999 to date.

None of these have been disclosed in his research work and publications.

Learn more

 * 2015, Institute of Medicine report - Review (8 December 2015, see also Institute of Medicine report)
 * 2016, 'Proof Positive (Revisited)' (14 Sep 2016)
 * 2016, ‘It was like being buried alive’: battle to recover from chronic fatigue syndrome