Psychoneuroimmunology of Cancer: Tooth Fairy Science?

James C. Coyne, Ph.D. University of Pennsylvania School of Medicine and

University Medical Center, Groningen jcoyne@mail.med.upenn.edu

Psychoneuroimmunology Psychoneuroimmunology (PNI)(PNI)

Study of the interaction between psychological processes and the nervous and immune systems of the human body.

Main interest is the direct influence of mental processes on physical health by way of the nervous and immune systems.

Promise is frequently made that a greater understanding of PNI will lead to psychological interventions improving the course and outcome of cancer.

PNI proponents claim stress is implicated in in the development course and outcome of cancer and behavioral interventions to reduce stress can be an important tool to treat and cure cancer, or at least extend the lives of cancer patients.

Psychoneuroimmunology Psychoneuroimmunology as a "Hot Area"as a "Hot Area"

Any true advances would be highly significant.

Standards are relaxed for deciding that a particular hypothesis had been confirmed.

Standards are relaxed for deciding that a previous finding had been replicated.

As a consequence, supposed positive findings often cannot be replicated.

Tooth Fairy Science seeks explanations for things before establishing that those things actually exist.

Tooth Fairy Scientists mistakenly think that if they have collected data that is consistent with their hypothesis, then they have collected data that confirms their hypothesis.

For example:

You could measure how much money the Tooth Fairy leaves under the pillow, whether she leaves more cash for the first or last tooth, whether the payoff is greater if you leave the tooth in a plastic baggie versus wrapped in Kleenex. You can get all kinds of good data that is reproducible and statistically significant. Yes, you have learned something. But you haven’t learned what you think you’ve learned, because you haven’t bothered to establish whether the Tooth Fairy really exists.

In approaching a hot area of research like PNI, you have to keep stopping and asking,

“Are a particular set of results interesting because they advance the field?”

OR

“Are they interesting results only because of some vague relevance claimed to interesting ideas that are not actually being tested?”

Classic components of causalityClassic components of causality

Association

Strength

Consistency

Specificity

Temporality

Biologic gradient

Plausibility

Coherence

Evidence from experimental manipulation

Analogy

Claims That Stress Claims That Stress Predicts Incidence, Predicts Incidence,

Progression, Outcome of Progression, Outcome of CancerCancer

Studies relating stress exposure to cancer incidence, progression, and outcome suffer from numerous methodological problems, and the better the study methodologically, the closer the hazards ratios cluster around null 1.0.

Recall bias among cases Exposure assessment after diagnosis of cancer Limited adjustment for biological factors

Flies in the OintmentFlies in the Ointment

Getting Hans Eysenck’s Fraudulent Getting Hans Eysenck’s Fraudulent Data Out of the LiteratureData Out of the Literature

● Co-authored papers with Grossarth-Maticek that claimed improbably high associations between personality and cancer and personality and smoking and published in own journal.

● Later it was revealed that he was paid substantially high amounts of money by attorneys for US tobacco companies to publish these data.

Coyne JC, Ranchor AV, Palmer SC. Meta-analysis of stress-related factors in cancer. Nat Rev Clin Oncol. 2010;7(5).

Ranchor AV, Sanderman R, Coyne JC. Invited Commentary: Personality as a Causal Factor in Cancer Risk and Mortality-Time to Retire a Hypothesis? American Journal of Epidemiology. 2010;172(4):386-8.

Coyne JC, Johansen C. Confirmatory bias and the persistent influence of discredited data in interpreting the stress-cancer link: Commentary on Michael et al. (2009). Health Psychol. 2011;30(3):374-5

Claims That Psychosocial Claims That Psychosocial Interventions Promote Interventions Promote the Survival of Cancer the Survival of Cancer

Patients...Patients...

No trial has ever found that psychotherapy improved the median survival time of women with metastatic breast cancer.

No trial in which survival was chosen as the outcome of interest ahead of time has demonstrated a survival effect for patients with any type of cancer, when psychotherapy was not confounded with improved medical surveillance or treatment.

  Coyne JC, Stefanek M, Palmer SC. Coyne JC, Stefanek M, Palmer SC. Psychotherapy and survival in cancer: the Psychotherapy and survival in cancer: the

conflict between hope and evidence. conflict between hope and evidence. Psychol Bull. Psychol Bull. 2007;133:367-394.2007;133:367-394.

“The results suggest that we can help breast cancer patients make positive steps that may help them live longer and make recurrence less likely. We already knew a psychological intervention program could help breast cancer patients to handle their stress, function more effectively, and improve their health. Now we know it does even more.”

Andersen, B. L., H. C. Yang, et al. (2008). Andersen, B. L., H. C. Yang, et al. (2008). "Psychologic Intervention Improves "Psychologic Intervention Improves

Survival for Breast Cancer Patients A Survival for Breast Cancer Patients A Randomized Clinical Trial." Randomized Clinical Trial." CancerCancer

113(12): 3450-3458.113(12): 3450-3458.

•No survival effect found in simple analyses, claims depend on inappropriate multivariate analyses.

•No differences between intervention and control groups in recurrence or survival.

•Psychosocial intervention consisting of a mixture of relaxation training, problem solving and health behavior promotion.

•Null and weak results across 8 measures of mood (no effects on mood), 15 measures of immune function, and 4 measures of adherence.

A Closer look at Andersen, et al.A Closer look at Andersen, et al.(2008). (2008). CancerCancer 113(12): 3450-3458. 113(12): 3450-3458.

Psychosocial Psychosocial Intervention, Immune Intervention, Immune

Function, and Function, and Progression of Cancer: Progression of Cancer:

Unproven MedicineUnproven Medicine

Weak or no effects, but positive results emphasized, strong confirmatory bias in reporting new results and recounting of past studies.

Doubtful clinical significance even if results were obtained.

Confused, simplistic view of role of immune system in cancer progression.

Claims That Psychosocial Claims That Psychosocial Intervention Strengthens the Intervention Strengthens the

Immune SystemImmune System

Each of the measures used in this literature represents only a small facet of a complex, highly redundant system. It would therefore be inappropriate to conclude that intervention-related changes in any specific immune parameter signal a state of "immune enhancement" or altered susceptibility to immune-mediated disease. The normal functioning range for most immune measures is very broad, and psychological interventions typically do not induce changes of sufficient magnitude to move people outside of these boundaries (p. 48).

Miller GE, Cohen S. Psychological Miller GE, Cohen S. Psychological interventions and the immune system: A interventions and the immune system: A meta-analytic review and critique. meta-analytic review and critique. Health Health

Psychology. Psychology. Jan 2001;20(1):47-63.Jan 2001;20(1):47-63.

How to Succeed in PNIHow to Succeed in PNI

Have lots of endpoints and ignore negative results in main analyses of primary endpoints.

Favor secondary analyses, subgroup analyses, and endpoints developed post hoc over negative findings for primary analyses.

Ignore methodological shortcomings that would make trial or meta analyses invalid.

How to Succeed in PNIHow to Succeed in PNI

• Present negative findings as if positive in subsequent publications and exaggerate findings that are positive.

Assess multiple endpoints and treat any significant finding as if it were a replication of past findings.

Create a false consensus and seeming unanimity in the literature by cherrypicking findings that can be construed as positive and ignoring the rest.

Missing Insight

Cancer is not one but many diseases likely to have multiple etiologies with a long course of development.

By the time that cancer can be detected and diagnosed, there have may have been numerous cascades such that biological processes cannot be reversed, and interventions in the biology of cancer may have very different effects than before the cascade was reached.

The ultimate tooth The ultimate tooth fairy science study?fairy science study?

Therapeutic Touch (TT)Therapeutic Touch (TT)

Therapeutic touch (TT) is a type of energy medicine whereby the therapist moves his or her hands over the patient’s “energy field,” allegedly directing the flow of chi or prana so the patient can heal. TT is based on the belief that each living thing has a “life energy field” which extends beyond the surface of the body and generates an aura.

This energy field can become unbalanced, misaligned, obstructed, or out of tune.

Therapeutic Touch (TT)Therapeutic Touch (TT)

Energy healers think they can feel and manipulate this energy field by making movements that resemble massaging the air a few inches above the surface of the patient’s body.

Energy healers also think that they can transfer some of their own life energy to the patient. These airy manipulations allegedly restore the energy field to a state of balance or harmony, to a proper alignment, or they unblock a clog in the field or transfer life energy from healer to patient. This restoration of integrity to the field is thought to make it possible for the body to heal itself.

TT. Hands-on healing, beginning with hands on feet, then knees, hips, bladder area, stomach, hands, elbows, shoulders, heart, throat, head, and back to the heart.

Mock Touch. Skeptical scientists trained to use identical hand placements as biofield healers, except asked not to intend to heal the patient when touching, rather to contemplate current and upcoming research-oriented studies and grants they were currently involved in.

Waitlist Control.

Therapeutic Touch (TT)Therapeutic Touch (TT)

Why study therapeutic touch?Why study therapeutic touch?

Chosen by Reverend Rosalyn L. Bruyere, Founder and Director of the Healing Light Center Church. She has studied extensively in areas of Egyptian temple symbology, Sacred geometry, ancient Mystery School rites, international shamanic practices, the pre-Buddhist Tibetan Bon-Po Ways, and various Native American Medicine traditions.

OutcomeOutcome

Investigators examined three primary outcomes, performed a post hoc secondary analysis of five scales of one of the outcomes, and a secondary analysis of cortisol.

With controls for multiple comparisons p< .05 would require p<.006.

OutcomeOutcome

Both therapeutic touch and mock treatment were different from waitlist control in reduction in fatigue.

Same pattern of results for quality of life, but no group differences in depression.

Therapeutic touch differed from mock treatment waitlist control for cortisol slope (p<.05), but effect disappears when multiple comparisons are taken into account.

Importance?Importance?

Flatter cortisol slopes have been shown to distinguish metastatic breast cancer and predict mortality in breast cancer patients.

There is a need to further examine the effects of specific processes of biofield healing on outcomes for cancer populations.

“…“…and seldom is heard a and seldom is heard a discouraging word”discouraging word”

All the positive results that fit.

No negative PNI findings acknowledged.

In approaching a hot area of research like PNI, you have to keep stopping and asking,

“Are a particular set of results interesting because they advance the field?”

OR

“Are they interesting results only because of some vague relevance claimed to interesting ideas that are not actually being tested?”