Relaxing vs Stimulating Acupressure for Fatigue Among Breast Cancer Patients: Lessons to be Learned

  • A chance to test your rules of thumb for quickly evaluating clinical trials of alternative or integrative  medicine in prestigious journals.
  • A chance to increase your understanding of the importance of  well-defined control groups and blinding in evaluating the risk of bias of clinical trials.
  • A chance to understand the difference between merely evidence-based treatments versus science-based treatments.
  • Lessons learned can be readily applied to many wasteful evaluations of psychotherapy with shared characteristics.

A press release from the University of Michigan about a study of acupressure for fatigue in cancer patients was churnaled  – echoed – throughout the media. It was reproduced dozens of times, with little more than an editor’s title change from one report to the next.

Fortunately, the article that inspired all the fuss was freely available from the prestigious JAMA: Oncology. But when I gained access, I quickly saw that it was not worth my attention, based on what I already knew or, as I often say, my prior probabilities. Rules of thumb is a good enough term.

So the article became another occasion for us to practice our critical appraisal skills, including, importantly, being able to make reliable and valid judgments that some attention in the media is worth dismissing out of hand, even when tied to an article in a prestigious medical journal.

The press release is here: Acupressure reduced fatigue in breast cancer survivors: Relaxing acupressure improved sleep, quality of life.

A sampling of the coverage:

sample coverage

As we’ve come to expect, the UK Daily Mail editor added its own bit of spin:

daily mailHere is the article:

Zick SM, Sen A, Wyatt GK, Murphy SL, Arnedt J, Harris RE. Investigation of 2 Types of Self-administered Acupressure for Persistent Cancer-Related Fatigue in Breast Cancer Survivors: A Randomized Clinical Trial. JAMA Oncol. Published online July 07, 2016. doi:10.1001/jamaoncol.2016.1867.

Here is the Trial registration:

All I needed to know was contained in a succinct summary at the Journal website:

key points

This is a randomized clinical trial (RCT) in which two active treatments that

  • Lacked credible scientific mechanisms
  • Were predictably shown to be better than
  • A routine care that lacked the positive expectations and support.
  • A primary outcome assessed by  subjectiveself-report amplified the illusory effectiveness of the treatments.

But wait!

The original research appeared in a prestigious peer-reviewed journal published by the American Medical Association, not a  disreputable journal on Beall’s List of Predatory Publishers.

Maybe  this means publication in a peer-reviewed prestigious journal is insufficient to erase our doubts about the validity of claims.

The original research was performed with a $2.65 million peer-reviewed grant from the National Cancer Institute.

Maybe NIH is wasting scarce money on useless research.

What is acupressure?

 According to the article

Acupressure, a method derived from traditional Chinese medicine (TCM), is a treatment in which pressure is applied with fingers, thumbs, or a device to acupoints on the body. Acupressure has shown promise for treating fatigue in patients with cancer,23 and in a study24 of 43 cancer survivors with persistent fatigue, our group found that acupressure decreased fatigue by approximately 45% to 70%. Furthermore, acupressure points termed relaxing (for their use in TCM to treat insomnia) were significantly better at improving fatigue than another distinct set of acupressure points termed stimulating (used in TCM to increase energy).24 Despite such promise, only 5 small studies24– 28 have examined the effect of acupressure for cancer fatigue.

290px-Acupuncture_point_Hegu_(LI_4)You can learn more about acupressure here. It is a derivative of acupuncture, that does not involve needles, but the same acupuncture pressure points or acupoints as acupuncture.

Don’t be fooled by references to traditional Chinese medicine (TCM) as a basis for claiming a scientific mechanism.

See Chairman Mao Invented Traditional Chinese Medicine.

Chairman Mao is quoted as saying “Even though I believe we should promote Chinese medicine, I personally do not believe in it. I don’t take Chinese medicine.”

 

Alan Levinovitz, author of the Slate article further argues:

 

In truth, skepticism, empiricism, and logic are not uniquely Western, and we should feel free to apply them to Chinese medicine.

After all, that’s what Wang Qingren did during the Qing Dynasty when he wrote Correcting the Errors of Medical Literature. Wang’s work on the book began in 1797, when an epidemic broke out in his town and killed hundreds of children. The children were buried in shallow graves in a public cemetery, allowing stray dogs to dig them up and devour them, a custom thought to protect the next child in the family from premature death. On daily walks past the graveyard, Wang systematically studied the anatomy of the children’s corpses, discovering significant differences between what he saw and the content of Chinese classics.

And nearly 2,000 years ago, the philosopher Wang Chong mounted a devastating (and hilarious) critique of yin-yang five phases theory: “The horse is connected with wu (fire), the rat with zi (water). If water really conquers fire, [it would be much more convincing if] rats normally attacked horses and drove them away. Then the cock is connected with ya (metal) and the hare with mao (wood). If metal really conquers wood, why do cocks not devour hares?” (The translation of Wang Chong and the account of Wang Qingren come from Paul Unschuld’s Medicine in China: A History of Ideas.)

Trial design

A 10-week randomized, single-blind trial comparing self-administered relaxing acupressure with stimulating acupressure once daily for 6 weeks vs usual care with a 4-week follow-up was conducted. There were 5 research visits: at screening, baseline, 3 weeks, 6 weeks (end of treatment), and 10 weeks (end of washout phase). The Pittsburgh Sleep Quality Index (PSQI) and Long-Term Quality of Life Instrument (LTQL) were administered at baseline and weeks 6 and 10. The Brief Fatigue Inventory (BFI) score was collected at baseline and weeks 1 through 10.

Note that the trial was “single-blind.” It compared two forms of acupressure, relaxing versus stimulating. Only the patient was blinded to which of these two treatments was being provided, except patients clearly knew whether or not they were randomized to usual care. The providers were not blinded and were carefully supervised by the investigators and provided feedback on their performance.

The combination of providers not being blinded, patients knowing whether they were randomized to routine care, and subjective self-report outcomes together are the makings of a highly biased trial.

Interventions

Usual care was defined as any treatment women were receiving from health care professionals for fatigue. At baseline, women were taught to self-administer acupressure by a trained acupressure educator.29 The 13 acupressure educators were taught by one of the study’s principal investigators (R.E.H.), an acupuncturist with National Certification Commission for Acupuncture and Oriental Medicine training. This training included a 30-minute session in which educators were taught point location, stimulation techniques, and pressure intensity.

Relaxing acupressure points consisted of yin tang, anmian, heart 7, spleen 6, and liver 3. Four acupoints were performed bilaterally, with yin tang done centrally. Stimulating acupressure points consisted of du 20, conception vessel 6, large intestine 4, stomach 36, spleen 6, and kidney 3. Points were administered bilaterally except for du 20 and conception vessel 6, which were done centrally (eFigure in Supplement 2). Women were told to perform acupressure once per day and to stimulate each point in a circular motion for 3 minutes.

Note that the control/comparison condition was an ill-defined usual care in which it is not clear that patients received any attention and support for their fatigue. As I have discussed before, we need to ask just what was being controlled by this condition. There is no evidence presented that patients had similar positive expectations and felt similar support in this condition to what was provided in the two active treatment conditions. There is no evidence of equivalence of time with a provider devoted exclusively to the patients’ fatigue. Unlike patients assigned to usual care, patients assigned to one of the acupressure conditions received a ritual delivered with enthusiasm by a supervised educator.

Note the absurdity of the  naming of the acupressure points,  for which the authority of traditional Chinese medicine is invoked, not evidence. This absurdity is reinforced by a look at a diagram of acupressure points provided as a supplement to the article.

relaxation acupuncture pointsstimulation acupressure points

 

Among the many problems with “acupuncture pressure points” is that sham stimulation generally works as well as actual stimulation, especially when the sham is delivered with appropriate blinding of both providers and patients. Another is that targeting places of the body that are not defined as acupuncture pressure points can produce the same results. For more elaborate discussion see Can we finally just say that acupuncture is nothing more than an elaborate placebo?

 Worth looking back at credible placebo versus weak control condition

In a recent blog post   I discussed an unusual study in the New England Journal of Medicine  that compared an established active treatment for asthma to two credible control conditions, one, an inert spray that was indistinguishable from the active treatment and the other, acupuncture. Additionally, the study involved a no-treatment control. For subjective self-report outcomes, the active treatment, the inert spray and acupuncture were indistinguishable, but all were superior to the no treatment control condition. However, for the objective outcome measure, the active treatment was more effective than all of the three comparison conditions. The message is that credible placebo control conditions are superior to control conditions lacking and positive expectations, including no treatment and, I would argue, ill-defined usual care that lacks positive expectations. A further message is ‘beware of relying on subjective self-report measures to distinguish between active treatments and placebo control conditions’.

Results

At week 6, the change in BFI score from baseline was significantly greater in relaxing acupressure and stimulating acupressure compared with usual care (mean [SD], −2.6 [1.5] for relaxing acupressure, −2.0 [1.5] for stimulating acupressure, and −1.1 [1.6] for usual care; P < .001 for both acupressure arms vs usual care), and there was no significant difference between acupressure arms (P  = .29). At week 10, the change in BFI score from baseline was greater in relaxing acupressure and stimulating acupressure compared with usual care (mean [SD], −2.3 [1.4] for relaxing acupressure, −2.0 [1.5] for stimulating acupressure, and −1.0 [1.5] for usual care; P < .001 for both acupressure arms vs usual care), and there was no significant difference between acupressure arms (P > .99) (Figure 2). The mean percentage fatigue reductions at 6 weeks were 34%, 27%, and −1% in relaxing acupressure, stimulating acupressure, and usual care, respectively.

These are entirely expectable results. Nothing new was learned in this study.

The bottom line for this study is that there was absolutely nothing to be gained by comparing an inert placebo condition to another inert placebo condition to an uninformative condition without clear evidence the control condition offered control of nonspecific factors – positive expectations, support, and attention. This was a waste of patient time and effort, as well as government funds, and produced results that were potentially misleading to patients. Namely, results are likely to be misinterpreted the acupressure is an effective, evidence-based treatment for cancer-related fatigue.

How the authors explained their results

Why might both acupressure arms significantly improve fatigue? In our group’s previous work, we had seen that cancer fatigue may arise through multiple distinct mechanisms.15 Similarly, it is also known in the acupuncture literature that true and sham acupuncture can improve symptoms equally, but they appear to work via different mechanisms.40 Therefore, relaxing acupressure and stimulating acupressure could elicit improvements in symptoms through distinct mechanisms, including both specific and nonspecific effects. These results are also consistent with TCM theory for these 2 acupoint formulas, whereby the relaxing acupressure acupoints were selected to treat insomnia by providing more restorative sleep and improving fatigue and the stimulating acupressure acupoints were chosen to improve daytime activity levels by targeting alertness.

How could acupressure lead to improvements in fatigue? The etiology of persistent fatigue in cancer survivors is related to elevations in brain glutamate levels, as well as total creatine levels in the insula.15 Studies in acupuncture research have demonstrated that brain physiology,41 chemistry,42 and function43 can also be altered with acupoint stimulation. We posit that self-administered acupressure may have similar effects.

Among the fallacies of the authors’ explanation is the key assumption that they are dealing with a specific, active treatment effect rather than a nonspecific placebo intervention. Supposed differences between relaxing versus stimulating acupressure arise in trials with a high risk of bias due to unblinded providers of treatment and inadequate control/comparison conditions. ‘There is no there there’ to be explained, to paraphrase a quote attributed to Gertrude Stein

How much did this project cost?

 According to the NIH Research Portfolios Online Reporting Tools website, this five-year project involved support by the federal government of $2,265,212 in direct and indirect costs. The NCI program officer for investigator-initiated  R01CA151445 is Ann O’Marawho serves ina similar role for a number of integrative medicine projects.

How can expenditure of this money be justified for determining whether so-called stimulating acupressure is better than relaxing acupressure for cancer-related fatigue?

 Consider what could otherwise have been done with these monies.

 Evidence-based versus science based medicine

Proponents of unproven “integrative cancer treatments” can claim on the basis of the study the acupressure is an evidence-based treatment. Future Cochrane Collaboration Reviews may even cite this study as evidence for this conclusion.

I normally label myself as an evidence-based skeptic. I require evidence for claims of the efficacy of treatments and am skeptical of the quality of the evidence that is typically provided, especially when it comes from enthusiasts of particular treatments. However, in other contexts, I describe myself as a science based medicine skeptic. The stricter criteria for this term is that not only do I require evidence of efficacy for treatments, I require evidence for the plausibility of the science-based claims of mechanism. Acupressure might be defined by some as an evidence-based treatment, but it is certainly not a science-based treatment.

For further discussion of this important distinction, see Why “Science”-Based Instead of “Evidence”-Based?

Broader relevance to psychotherapy research

The efficacy of psychotherapy is often overestimated because of overreliance on RCTs that involve inadequate comparison/control groups. Adequately powered studies of the comparative efficacy of psychotherapy that include active comparison/control groups are infrequent and uniformly provide lower estimates of just how efficacious psychotherapy is. Most psychotherapy research includes subjective patient self-report measures as the primary outcomes, although some RCTs provide independent, blinded interview measures. A dependence on subjective patient self-report measures amplifies the bias associated with inadequate comparison/control groups.

I have raised these issues with respect to mindfulness-based stress reduction (MBSR) for physical health problems  and for prevention of relapse in recurrence in patients being tapered from antidepressants .

However, there is a broader relevance to trials of psychotherapy provided to medically ill patients with a comparison/control condition that is inadequate in terms of positive expectations and support, along with a reliance on subjective patient self-report outcomes. The relevance is particularly important to note for conditions in which objective measures are appropriate, but not obtained, or obtained but suppressed in reports of the trial in the literature.

Why the scientific community needs the PACE trial data to be released

To_deposit_or_not_to_deposit,_that_is_the_question_-_journal.pbio.1001779.g001University and clinical trial investigators must release data to a citizen-scientist patient, according to a landmark decision in the UK. But the decision could still be overturned if the University and investigators appeal. The scientific community needs the decision to be upheld. I’ll argue that it’s unwise for any appeal to be made. The reasons for withholding the data in the first place were archaic. Overturning of the decision would set a bad precedent and would remove another tooth from almost toothless requirements for data sharing.

We didn’t need Francis Collins, Director of National Institutes of Health to tell us what we already knew, the scientific and biomedical literature is untrustworthy.

And there is the new report from the UK Academy of Medical Sciences, Reproducibility and reliability of biomedical research: improving research practice.

There has been a growing unease about the reproducibility of much biomedical research, with failures to replicate findings noted in high-profile scientific journals, as well as in the general and scientific media. Lack of reproducibility hinders scientific progress and translation, and threatens the reputation of biomedical science.

Among the report’s recommendations:

  • Journals mandating that the data underlying findings are made available in a timely manner. This is already required by certain publishers such as the Public Library of Science (PLOS) and it was agreed by many participants that it should become more common practice.
  • Funders requiring that data be released in a timely fashion. Many funding agencies require that data generated with their funding be made available to the scientific community in a timely and responsible manner

A consensus has been reached: The crisis in the trustworthiness of science can be only overcome only if scientific data are routinely available for reanalysis. Independent replication of socially significant findings is often unfeasible, and unnecessary if original data are fully available for inspection.

Numerous governmental funding agencies and regulatory bodies are endorsing routine data sharing.

The UK Medical Research Council (MRC) 2011 policy on data sharing and preservation  has endorsed principles laid out by the Research Councils UK including

Publicly funded research data are a public good, produced in the public interest, which should be made openly available with as few restrictions as possible in a timely and responsible manner.

To enable research data to be discoverable and effectively re-used by others, sufficient metadata should be recorded and made openly available to enable other researchers to understand the research and re-use potential of the data. Published results should always include information on how to access the supporting data.

The Wellcome Trust Policy On Data Management and Sharing opens with

The Wellcome Trust is committed to ensuring that the outputs of the research it funds, including research data, are managed and used in ways that maximise public benefit. Making research data widely available to the research community in a timely and responsible manner ensures that these data can be verified, built upon and used to advance knowledge and its application to generate improvements in health.

The Cochrane Collaboration has weighed in that there should be ready access to all clinical trial data

Summary results for all protocol-specified outcomes, with analyses based on all participants, to become publicly available free of charge and in easily accessible electronic formats within 12 months after completion of planned collection of trial data;

Raw, anonymised, individual participant data to be made available free of charge; with appropriate safeguards to ensure ethical and scientific integrity and standards, and to protect participant privacy (for example through a central repository, and accompanied by suitably detailed explanation).

Many similar statements can be found on the web. I’m unaware of credible counterarguments gaining wide acceptance.

toothless manYet, endorsements of routine sharing of data are only a promissory reform and depend on enforcement that has been spotty, at best. Those of us who request data from previously published clinical trials quickly realize that requirements for sharing data have no teeth. In light of that, scientists need to watch closely whether a landmark decision concerning sharing of data from a publicly funded trial is appealed and overturned.

The Decision requiring release of the PACE data

The UK’s Information Commissioner’s Office (ICO) ordered Queen Mary University of London (QMUL) on October 27, 2015 to release anonymized from the PACE chronic fatigue syndrome trial data to an unnamed complainant. QMUL has 28 days to appeal.

Even if scientists don’t know enough to care about Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, they should be concerned about the reasons that were given in a previous refusal to release the data.

I took a critical look at the long-term follow up results for the PACE trial in a previous Mind the Brain blog post  and found fatal flaws in the authors’ self-congratulatory interpretation of results. Despite authors’ claims to the contrary and their extraordinary efforts to encourage patients to report the intervention was helpful, there were simply no differences between groups at follow-up

Background on the request for release of PACE data

  • A complainant requested release of specific PACE data from QMUL under the Freedom of Information Act.
  • QMUL refused the request.
  • The complainant requested an internal review but QMUL maintained its decision to withhold the data.
  • The complainant contacted the ICO with concerns about how the request had been handled.
  • On October 27, 2015, the ICO sided with the complainant and order the release of the data.

A report outlines Queen Mary’s arguments for refusing to release the data and the Commissioner’s justification for siding with the patient requesting the data be released.

Reasons the request release of data was initially refused

The QMU PACE investigators claimed

  • They were entitled to withhold data prior to publication of planned papers.
  • An exemption to having to share data because data contained sensitive medical information from which it was possible to identify the trial participants.
  • Release of the data might harm their ability to recruit patients for research studies in the future.

The QMU PACE researchers specifically raised concerns about a motivated intruder being able to facilitate re-identification of participants:

In relation to a motivated intruder being able facilitate re-identification of participants, the University argued that:

“The PACE trial has been subject to extreme scrutiny and opponents have been against it for several years. There has been a concerted effort by a vocal minority whose views as to the causes and treatment of CFS/ME do not comport with the PACE trial and who, it is QMUL’s belief, are trying to discredit the trial. Indeed, as noted by the editor of the Lancet, after the 2011 paper’s publication, the nature of this comprised not a ‘scientific debate’ but an “orchestrated response trying to undermine the credibility of the study from patient groups [and]… also the credibility of the investigators and that’s what I think is one of the other alarming aspects of this. This isn’t a purely scientific debate; this is going to the heart of the integrity of the scientists who conducted this study.”

Magneto_430Bizarre. This is obviously a talented masked motivated intruder. Do they have evidence that Magneto is at it again? Mostly he now is working with the good guys, as seen in the help he gave Neurocritic and me.

Let’s think about this novel argument. I checked with University of Pennsylvania bioethicist Jon Merz, an expert who has worked internationally to train researchers and establish committees for the protection of human subjects. His opinion was clear:

The litany of excuses – not reasons – offered by the researchers and Queen Mary University is a bald attempt to avoid transparency and accountability, hiding behind legal walls instead of meeting their critics on a level playing field.  They should be willing to provide the data for independent analyses in pursuit of the truth.  They of course could do this willingly, in a way that would let them contractually ensure that data would be protected and that no attempts to identify individual subjects would be made (and it is completely unclear why anyone would care to undertake such an effort), or they can lose this case and essentially lose any hope for controlling distribution.

The ‘orchestrated response to undermine the credibility of the study’ claimed by QMU and the PACE investigators, as well as issue being raised of the “integrity of the scientists who conducted the study” sounds all too familiar. It’s the kind of defense that is heard from scientists under scrutiny of the likes of Open Science Collaborations, as in psychology and cancer. Reactionaries resisting post-publication peer review say we must be worried about harassment from

“replication police” “shameless little bullies,” “self-righteous, self-appointed sheriffs” engaged in a process “clearly not designed to find truth,” “second stringers” who were incapable of making novel contributions of their own to the literature, and—most succinctly—“assholes.”

Far fetched? Compare this to a QMU quote drawn from the National Radio, Australian Broadcast Company April 18, 2011 interview of Richard Horton and PACE investigator Michael Sharpe in which former Lancet Editor Richard Horton condemned:

A fairly small, but highly organised, very vocal and very damaging group of individuals who have…hijacked this agenda and distorted the debate…

dost thou feel‘Distorted the debate’? Was someone so impertinent as to challenge investigators’ claims about their findings? Sounds like Pubpeer  We have seen what they can do.

Alas, all scientific findings should be scrutinized, all data relevant to the claims that are made should be available for reanalysis. Investigators just need to live with the possibility that their claims will be proven wrong or exaggerated. This is all the more true for claims that have substantial impact on public policy and clinical services, and ultimately, patient welfare.

[It is fascinating to note that Richard Horton spoke at the meeting that produced the UK Academy of Medical Sciences report to which I provided a link above. Horton covered the meaning in a Lancet editorial  in which he amplified the sentiment of the meeting: “The apparent endemicity of bad research behaviour is alarming. In their quest for telling a compelling story, scientists too often sculpt data to fit their preferred theory of the world.” His editorial echoed a number of recommendations of the meeting report, but curiously omitted mentioning of data sharing.]

jacob-bronowski-scientist-that-is-the-essence-of-science-ask-anFortunately the ICO has rejected the arguments of QMUL and the PACE investigators. The Commissioner found that QMUL and the PACE investigators incorrectly interpreted regulations in their withholding of the data and should provide the complaint with the data or risk being viewed as in contempt of court.

The 30-page decision is a fascinating read, but here’s an accurate summary from elsewhere:

In his decision, the Commissioner found that QMUL failed to provide any plausible mechanism through which patients could be identified, even in the case of a “motivated intruder.” He was also not convinced that there is sufficient evidence to determine that releasing the data would result in the mass exodus of a significant number of the trial’s 640 participants nor that it would deter significant numbers of participants from volunteering to take part in future research.

Requirements for data sharing in the United States have no teeth and situation would be worsened by reversal of ICO decision

Like the UK, the United States supposedly has requirements for sharing of data from publicly funded trials. But good luck in getting support from regulatory agencies associated with funding sources for obtaining data. Here’s my recent story, still unfolding – or maybe, sadly, over, at least for now.

For a long time I’ve fought my own battles about researchers making unwarranted claims that psychotherapy extend the lives of cancer patients. Research simply does not support the claim. The belief that psychological factors have such influence on the course and outcome of cancer sets up cancer patients to be blamed and to blame themselves when they don’t overcome their disease by some sort of mind control. Our systematic review concluded

“No randomized trial designed with survival as a primary endpoint and in which psychotherapy was not confounded with medical care has yielded a positive effect.”

Investigators who conducted some of the best ambitious, well-designed trials to test the efficacy of psychological interventions on cancer but obtained null results echoed our assessment. The commentaries were entitled “Letting Go of Hope” and “Time to Move on.”

I provided an extensive review of the literature concerning whether psychotherapy and support groups increased survival time in an earlier blog post. Hasn’t the issue of mind-over-cancer been laid to rest? I was recently contacted by a science journalist interested in writing an article about this controversy. After a long discussion, he concluded that the issue was settled — no effect had been found — and he could not succeed in pitching his idea for an article to a quality magazine.

But as detailed here one investigator has persisted in claims that a combination of relaxation exercises, stress reduction, and nutritional counseling increases survival time. My colleagues and I gave this 2008 study a careful look.  We ran chi-square analyses of basic data presented in the paper’s tables. But none of our analyses of group assignment on mortality more disease recurrence was significant. The investigators’ claim of an effect depended on dubious multivariate analyses with covariates that could not be independently evaluated without a look at the data.

The investigator group initially attempted to block publication of a letter to the editor, citing a policy of the journal Cancer that critical letters could not be published unless investigators agreed to respond and they were refusing to respond. We appealed and the journal changed its policy and allowed us additional length to our letter.

We then requested from the investigator’s University Research Integrity Officer the specific data needed to replicate the multivariate analyses in which the investigators claimed an effect on survival. The request was denied:

The data, if disclosed, would reveal pending research ideas and techniques. Consequently, the release of such information would put those using such data for research purposes in a substantial competitive disadvantage as competitors and researchers would have access to the unpublished intellectual property of the University and its faculty and students.

Recall that we were requesting in 2014 specific data needed to evaluate analyses published in 2008.

I checked with statistician Andrew Gelman whether my objections to the multivariate analyses were well-founded and he agreed they were.

Since then, another eminent statistician Helena Kraemer has published an incisive critique of reliance in a randomized controlled trial on multivariate analyses and simple bivariate analyses do not support the efficacy of interventions. She labeled adjustments with covariates as a “source of false-positive findings.”

We appealed to the US Health and Human Services Office of Research Integrity  (ORI) but they indicated no ability to enforce data sharing.

Meanwhile, the principal investigator who claimed an effect on survival accompanied National Cancer Institute program officers to conferences in Europe and the United States where she promoted her intervention as effective. I complained to Robert Croyle, Director, NCI Division of Cancer Control and Population Sciences who twice has been one of the program officer’s co-presenting with her. Ironically, in his capacity as director he is supposedly facilitating data sharing for the division. Professionals were being misled to believe that this intervention would extend the lives of cancer patients, and the claim seemingly had the endorsement NCI.

I told Robert Croyle  that if only the data for the specific analyses were released, it could be demonstrated that the claims were false. Croyle did not disagree, but indicated that there was no way to compel release of the data.

The National Cancer Institute recently offered to pay the conference fees to the International Psycho-Oncology Congress in Washington DC of any professionals willing to sign up for free training in this intervention.

I don’t think I could get any qualified professional including  Croyle to debate me publicly as to whether psychotherapy increases the survival of cancer patients. Yet the promotion of the idea persists because it is consistent with the power of mind over body and disease, an attractive talking point

I have not given up in my efforts to get the data to demonstrate that this trial did not show that psychotherapy extends the survival of cancer patients, but I am blocked by the unwillingness of authorities to enforce data sharing rules that they espouse.

There are obvious parallels between the politics behind persistence of the claim in the US for psychotherapy increasing survival time for cancer patients and those in the UK about cognitive behavior therapy being sufficient treatment for schizophrenia in the absence of medication or producing recovery from the debilitating medical condition, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. There are also parallels to investigators making controversial claims based on multivariate analyses, but not allowing access to data to independently evaluate the analyses. In both cases, patient well-being suffers.

If the ICO upholds the release of data for the PACE trial in the UK, it will pressure the US NIH to stop hypocritically endorsing data sharing and rewarding investigators whose credibility depends on not sharing their data.

As seen in a PLOS One study, unwillingness to share data in response to formal requests is

associated with weaker evidence (against the null hypothesis of no effect) and a higher prevalence of apparent errors in the reporting of statistical results. The unwillingness to share data was particularly clear when reporting errors had a bearing on statistical significance.

Why the PACE investigators should not appeal

In the past, PACE investigators have been quite dismissive of criticism, appearing to have assumed that being afflicted with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis precludes a critic being taken seriously, even when the criticism is otherwise valid. However, with publication of the long-term follow-up data in Lancet Psychiatry, they are now contending with accomplished academics whose criticisms cannot be so easily brushed aside. Yes, the credibility of the investigators’ interpretations of their data are being challenged. And even if they do not believe they need to be responsive to patients, they need to be responsive to colleagues. Releasing the data is the only acceptable response and not doing so risks damage to their reputations.

QMUL, Professors White and Sharpe, let the People’s data go.