EXPLORE March-April 2019, Vol 15, No 2. John Weeks: Guest editorial

Kopioitu EXPLORE-lehdestä 29.9.2020:

Musings on Patient Care and  polarization After JAMA Oncologys Erroneous Report That Complementary Medicine Kills

John Weeks

If I position myself as a consumer of oncology services I am one – I would find myself extremely confused by recent media on the use of cancer-related treat- ment that is a complement to typical treat- ment but not typically part of mainstream oncology. After a research team led by a radiation oncologist from Yale reported in July 2018 in the pages of the esteemed JAMA Oncology that such a choice was associated with greater risk of death,1 The New York Times trumpeted their findings in a headline: “People who used herbs, acupuncture and other complementary treatments tended to die earlier than those who didn’t.”2

The biggest problem with this conclu- sion is not that the esteemed journal and Yale researchers got it fundamentally wrong basically every which way, as I will show below. The more significant damage is the downstream confusion sown by the media in the public and in practitioner communities. Many from both stakeholder groups patient and practitioner – are trying earnestly to under- stand if there are any methods to avoid or ameliorate the damage from the necessary but brutal cutting out of tumors and organs, radiating tissue, and infusing toxic chemicals throughout the human body that make up the lion’s share of conven- tional oncology treatment.

Those wondering whether the public could benefit from conscientious guid- ance only need review other recent, con- flicting news. A Harris poll for the American Society for Clinical Oncologists (ASCO) found that a shocking 40% of adult Americans believe that “alternative medicine” can cure cancer.3 This came

shortly after ASCO endorsed the value in multiple “complementary medicine” approaches. It became the second major cancer organization in recent years to endorse an integrative oncology guideline from the Society for Clinical Oncology.4,5 And it came despite a widely-publicized 2017 study from the same Yale group – this one unchallenged by integrative doc- tors6 that concluded that those who chose to use “alternative medicine” in lieu of conventional cancer treatment were kill- ing themselves.7 Meantime, a rash of Go- Fund-Me sites are proliferating of individ- uals seeking money for pursuing spurious healing promises.8

Rather than walk into this sensitive environment in a spirit that reflects the depth of the life-and-death individual and public health issues at stake, what this Yale study effectively did for those invol- untarily boarded onto the cancer treat- ment journey was the classic high-school prank. They took a critical directional traf- fic pointer and flipped it the other direction.


The news of the JAMA Oncology study arrived via a Google Alerts notice about the New York Times article. Multiple other high and lower impact story alerts fol- lowed. The media was all over this one.

I responded first to the headline as a for- mer cancer patient. I share this here in part for context, hoping that a bit of one patient story will make less abstract the impact of what the Yale researchers and

JAMA Oncology chose to do. Conven- tional cancer treatment involves killing processes that I came to know intimately. In the moment that one feels the dark blow to the spirit of the diagnosis that life may end sooner rather than one has imag- ined, treatment recommendations pile on as body blows. The abstractions of “adverse events” become real. The cut- radiate-poison trio was all part of the treat- ment for tonsillar cancer that National Clinical Cancer Network guidelines included, and MY WIFE AND I chose. In the best outcome, the promise was sur- vival and a shadowy “new normal” beset by the likelihood of multiple long-term adverse consequences. A direct-speaking academic physician who heads his depart- ment at the University of Washington with whom I consulted early on prepared me for the grueling path. He called this tonsillar cancer treatment, with its multi- ple ways of harming drinking, eating, speaking, breathing, hearing, smelling and tasting “next to bone-marrow transplant, one of the most brutal things we do.”

As a patient  with then 25 years  in the integrative health field, I was privileged with access to the best information and counsel on complementary medicine practi- ces and practitioners. In the period before, during and in the first few months of intense healing after the treatment, I experi- mented with a multitude of complementary treatments. My goals were to soften the blows of the multiple affronts: anxiety, headache, burned tissue, constipation, fear, sleeplessness, and other aggravations a human being might experience when under such furious attacks on one’s tissues, mind and spirit. I experimented, and in the end felt these forays into complementary medicine approaches were quite useful for mind and body. So as a patient, my responses to the Johnson-Yu outcomes were disbelief and anger. My anger came from quickly recognizing that this mes- sage that complementary medicine kills would drive some people who were com- plementary medicine na€ıve away from helpful tools. And it would make skepti- cal oncologists even more firm in their resolve, and sway agnostics or the disinterested against. They would be rea- sonably excused from exploring comple- mentary therapies and much less likely to be referring for them. My personal experience made me focus on the human suffering that the message of this article would cause.


While I was experiencing this “news” from a patient perspective, I began to examine the study from my professional experience as a chronicler and writer in the integrative health field. The following are among the key points in the study, extracted from the authors’ abstract. The study was an obser- vational, data-mining project that began in an impressive motherload: 1,901,815 patients in the National Cancer Database who were diagnosed with nonmetastatic breast, prostate, lung, or colorectal cancer between January 1, 2004, and December 31, 2013. (Given the authority of the source and the enormous apparent N, media and other observers would likely quickly lean toward trust.) Patients were matched on age, clinical group stage, Charlson-Deyo comorbidity score, insurance type, race/ethnicity, year of diagnosis, and cancer type. Use of “com- plementary medicine” was defined as “Other-Unproven: Cancer treatments administered by nonmedical personnel.” Those who meet this criterion had to have used at least one conventional cancer treatment modality. They defined these as surgery, radiotherapy, chemotherapy, and/or hormone therapy.

The Johnson and Yu team’s results are based on 258 patients that were in the complementary medicine group. They found that these patients who chose com- plementary medicine    defined as such “did not have a longer delay to initiation of [conventional cancer treatment CCT] but had higher refusal rates of surgery.”

Use of complementary medicine was asso- ciated with poorer 5-year overall survival compared with those who did not chose and was independently associated with greater risk of death “in a multivariate model that did not include treatment delay or refusal.” They then noted that there was “no significant association between complementary medicine and survival once treatment delay or refusal was included in the model.” Finally, the marquis conclusion that captured the media: “In this study, patients who received [complementary medicine] were more likely to refuse additional [conven- tional cancer treatment] and had a higher risk of death. The results suggest that mor- tality risk associated with complementary medicine was mediated by the refusal of CCT.”

In the New York Times account, the following were implicated as examples of “complementary therapies”: herbs, vita- mins, traditional Chinese medicine, homeopathy, naturopathy, yoga, acupunc- ture and others. The Yale authors included an expanded list: “herbs/botanicals, vitamins and minerals, probiotics, Ayurvedicmedicine traditional Chinese medicine, homeopathy and naturopathy, deep breathing,  yoga,  Tai  Chi,  Qi  Gong, acupuncture, chiropractic or osteopathic manipulation, meditation, massage, prayer, special diets, progressive relaxation, and/or guided imagery.” Of these, the authors note in their discussion, “except for mind-body therapies that have been shown to improve quality-of-life, there is limited to no evidence that these therapies have been shown to improve cancer sur- vival as a CM.” (It is notable here, as a patient, that the authors put the accent is on “improving cancer survival” when much complementary medicine use tar- gets the more limited goal of more com- fortably surviving the assaults of their treatments.)


Rather than stew in my own prejudices, I turned to academic medicine colleagues with expertise in integrative oncology research for perspective. A first response came from University of California at San Francisco oncologist Donald Abrams, MD. He replied via email in a long paragraph-length note that included the following points [personal communica- tion August 3, 2018]. He noted that the researchers’ definition of “complemen- tary”  was confounded with “alterna- tive.” He defined the former as “practices used to complement usual oncologic care” and the latter as “therapies used instead of.” Notably, Abrams’ definitions align with those of Webster, and with common usage. As the Chinese scholar Confucius is attributed with saying: “The beginning of wisdom is to call things by their proper name.” Complements are not alternatives. With that clarified, Abrams remarked that “even the authors note that if one removes those who have delayed treatment or refused treatment             thus who would seem to view their CM as ‘alternative’ rather than purely ‘complementary’                        that ‘all of the differences go away.’” Lynda Bal- neaves, RN, PhD, president of the Soci- ety for Integrative Oncology put a researcher’s name to this bald error: “mis- classification bias.”9 Take out those who were not using these therapies as comple- ments but instead as alternatives, and the bottom falls out of the paper. Johnson and Lu and JAMA Oncology are left with nothing to publish except that those who use non-conventional therapies as com- plements to conventional care do at least as well as those who use conventional care alone. The outcomes require the authors                                and JAMA Oncology – to endorse a definition of complementary that is misaligned with common use. If a patient uses one “complementary medi- cine” but also refuses treatment, it is the treatment refusal and not the comple- mentary medicine that may leave him or

her with a shortened life.

Abrams spoke next to the statistical basis for the analysis: “Really, out of 1,901,557 people in the cohort, they only find 258 using these oddly defined treatments?” He knew that multiple surveys have established that at least 30% 50% of people with can- cer use complementary medicine.10 Then he turned to the decision of Johnson and Yu to define complementary medicine as practi- ces delivered by “non-medical providers.” (Balneaves separately wondered “why would they use a definition of ‘complementary’ from 1998?”) Abrams, as an integrative oncology clinician routinely prescribing complementary medicine in oncology care via a position in an academic medical cen- ter, as part of a growing global society of similarly placed practitioners through SIO,11 and conscious of the work in cancer-related treatment of literally thousands licensed medical doctors, nurses, acupuncturists, massage therapies, naturopathic doctors, and others, was terse: “The definition is retro and uninformed.” He concluded gener- ously: “A poor paper in my opinion.”


Balneaves suggested I secure the view of a statistician. Scott Mist, Ph.D., MAcOM, M.S., M.A., LAc is an assistant professor for anesthesiology and perioperative medi- cine at Oregon Health Sciences University School of Medicine. He serves as the asso- ciate editor for statistics at JACM Para- digm, Practice and Policy Advancing Integrative Health (The Journal of Alterna- tive and Complementary Medicine) to which I contribute as editor-in-chief. Mist e-mailed a bulleted response within hours of the request. Given the importance of clarifying whether complementary thera- pies are in fact life-threatening, I asked Mist to edit his e-mail for broader con- sumption. The full text has been made publicly available and I presented it via email to Johnson and Yu.12 (More on that below.)

The two points to which Mist most called attention were each highlighted by the others. He joined Abram and Bal- neaves in raising a bright red flag over the decision to focus on just 258 of 1,901,815 patients that the authors put in the CM group. Mist points out that, elsewhere in the paper, the authors note that multiple surveys have found that between 48% and 88% of people with various types of can- cer use some complementary methods. Mist did the math: “There should have been between 836,799 and 1,673,597 CM users. But they found [just 258] less than 0.01%. That should have stopped the study right there … There is no way that less than 1/100th of the population is rep- resentative of the population of CM users.” Common sense – if not Webster in this case – wonders how Johnson-Yu and their team could comfortably use this .01% of a population to capture outcomes on what evidence says was somewhere between 3243 and 6487 times that.

Mist also challenged the statistical method and concluded that the issues found of individuals whose lives were

shortened are with outliers: “Given that the authors were drilling down into subpo- pulations (28 cases having died within  5 years 0.0015% of the sample) within the types of cancer (186 cases (0.0098% of the sample), I feel it is safe to say it is a case of outliers driving the analysis. Should their statement that between 48% and 88% of the population are using CM be true, their analysis suggests that they should have seen 99,000 and 198,000 such incidents within their database.”

Mist’s analysis raised additional ques- tions. He notes that, given what is known about use of complementary medicine among those with cancer, “at least half or more of their control group is also doing CM but it wasn’t captured.” Both the sub- jects and comparators are suspect. He questions assumptions behind other extrapolations. An example: a frequently used method for establishing a set of com- parators was inappropriately applied. Mist concludes with what he considered the other most significant issue: “They say that when controlling for refusal rates and delays, there is no difference in the sur- vival rates. Therefore, it can’t be the CM treatments that are the difference.”


The statistical data quite likely have an additional, major error that is known col- loquially as “garbage in/garbage out.” Patients are famously reticent to share their use of non-conventional therapies with their doctors, whether out of concern for physician disapproval or because they assume that their physicians would not know anything about complementary medicine. Mist notes “several reasons why there are only a few reporting CM treat- ments and all of the reasons indicate that the database isn’t suited to this analysis. The first reason is that this information is poorly recorded. Other research indicates that [medical doctors] are very bad at recording CM treatments. Patients com- monly are using other modalities and are afraid to discuss it with their practitioner. Further, [electronic medical records] are not well set up to record this kind of data and it is not in the training of most MDs who are already pressed with shorter visits. [Thus], the patients that are in the data- base may be better communicators and are relatively unique. As such, they may not be representative of the greater

population of CM users.” That such com- munication remains rare, abbreviated, and unreliable inputs for a dependable dataset is evident in two recent studies from Mayo Clinic researchers.13,14

Considering the 2003 2016 years of data capture, most medical records did not have questions relative to complemen- tary or alternative medicine use. And, con- sidering the confusion over language that we are clearly still dealing with today, what are the chances that either the patient or the physician or both knew how to dis- tinguish what was used as an “alternative” and what was used as “complementary.” The authors’ conclusion that “our work demonstrates that patients who undergo alternative medicine and complementary medicine are often behaving similarly in refusing treatment” may be better stated as: Researchers who confound the differ- ence between alternative and complemen- tary will find that the two, when merged, yield similar outcomes. Garbage out.

I sent Johnson and Lu Mist’s analysis, and the comments of the integrative oncologists and subsequently reported the exchange.15 Johnson responded: “Thanks for reaching out. I’m a huge proponent of critical analysis of scientific work. The co- authors and I believe that these results strengthen the position of alternative prac- titioners and integrative oncologists, who recommend evidence-based practices for cancer patients, by encouraging treatment adherence to proven therapies while seek- ing to improve patient quality of life. We would love to work with members of the integrative oncology community to test these findings prospectively.” Then he added: “Regarding critiques to the paper and statistics, we clearly discussed the limi- tations of the data, analysis and interpreta- tion thereof” and he then copied that section of the paper. One  wishes  JAMA

Oncology  had  required  the  authors  to engage a point-by-point rebuttal of such a review as Mist’s prior to considering publication.


44 88% who are likely to use some com- plementary therapies and thus be more likely to delay or refuse treatment that could presumably lengthen life span the paper may be deemed to have value to an oncologist or medical team. They would know that at some point in treatment, a person who is known to be using comple- mentary therapies for other issues may be more likely to not go along with treatment recommendations. The patient may be more likely to question whether the course the oncologist recommends is what they wish to follow.

The patient’s reasons for diverging could be many. The authors acknowledge, as a study weakness, that they have not sorted the motives of these users of com- plementary therapies who chose an alter- native course to the recommendations of their oncologists. For instance, a person who has used one or more complementary medicines early in treatment may be more likely to decide to forego an ensuing course of chemotherapy or radiation than an aggressive oncologist is prescribing. The person may decide to choose the enjoyment of tastes and food and a decent recollection of who they are as a human being in the last months of their life instead of spending them under another round of poisonous assault. The result may be to choose X months living closer to the person they’ve known the rest of their lives instead of Y months more under additional brutalization of an already weakened self, with no hair, and senses compromised by the treatments. How much of the delay and refusal may be linked to such choices? One conclusion of this study could be: Users of complemen-

tary medicine who make decisions to not

engage heroic quality of life-damaging services are associated with signicant overall cost savings.

While I have no evidence to support this, I feel comfortable speculating that those who show the personal agency to seek out and use complementary therapies for a first round of treatment may be more likely to make an informed choice to not prolong life at all costs and choose qual- ity of life over quantity. They might, if a first round fails or a cancer has come back, be more likely to choose to live more like themselves rather than reengage the spec- ter of additional hellish torments from last ditch therapeutics. Meditation and self- reflection may make one susceptible to making choices that refuse the oncologist’s kitchen sink.

What is easily lost in the context of the New York Times headline (“People who used herbs, acupuncture and other com- plementary treatments tended to die ear- lier than those who didn’t”) and the longer list of complementary treatments, noted above, that the authors list, is that the Johnson-Lu paper does not say that use of acupuncture or massage or mindful- ness or herbs or hypnotherapy or any of the others hastens death. The paper, and the coverage, only appear to pass such judgement. These practices – if the John- Yu conclusions are in fact representative – are all merely tarnished by association with the decision of an individual, for whatever reason, to delay or forego con- ventional treatment.


If common sense guides one to the mis- classification bias of “complementary” as “alternative” the midnight prank switch- ing the road signs – and to further dismay that only 248 needles in the haystack of 1,901,815 should somehow be made to adequately represent between 836,799 and 1,673,597 complementary medicine users, then add in a dataset that is inappropriate for the questions asked of it – then com- mon sense might as easily ask why the authors, or JAMA Oncology, should not retract the article.

I asked SIO president Balneaves directly. She had been part of an SIO team that crafted a response letter to JAMA Oncology that was accepted for pub- lication. SIO did not call for retraction. Balneaves explained: “It’s a good question. Retractions are often focused on method- ological issues and errors or on violations of ethics. I believe there is a major misclas- sification bias. But is that reason enough? Some would argue that’s not sufficient cause for retraction.” She added: “I did seriously wonder why JAMA Oncology took the paper, there are so many signifi- cant problems.”

Nor was retraction the call from a com- plementary and integrative medicine research group at the University of Duis- burg-Essen in Germany. They concluded in their rejected letter that “It might have been more precise to conclude that ‘patients who use unproven cancer treat- ments administered by non-medical per- sonnel were more likely to refuse conventional cancer treatment and had a higher risk of death.” The reason given for their rejection was that the journal had already received a variety of other responses. [Personal communication, Holger Cramer, August 23, 2018.] Another integrative oncology group, the Oncology Association of Naturopathic Physicians, staked a similar position as the German trio, also stopping short of a call for retraction.16

Some with whom I have informally spo- ken who support retraction respond with cynical dismay that the organized integrative oncology community had not chosen a harder line. More than one wondered aloud if the researchers are fearful of jeopardizing their chances of one day publishing in JAMA. What is clear from the interviews is that the integrative oncology community is most interested in practicing in this micro- cosm of its relationship with the oncology community over the Johnson-Lu article what it seeks, generally in its movement toward an integrative model: engage dia- logue and action, over the long term, to enhance cancer treatment, rather than to make the one loud noise of a retraction.


When I asked about retraction, Balneaves shared her preferred response: “What I’d like to see at least is a published dialogue and have the authors respond.” She reflected: “It’s too bad that the authors didn’t just connect with researchers knowl- edgeable in integrative oncology before doing this work. There are a lot of us out there. We need more of the kind of under- standing that a paper like this could pro- vide. But we’ve got to get the questions and methodology right.”

Her question is a good one, especially given the severity of the conclusions and the media response that might have been anticipated. This devaluation of interpro- fessional relationships began early in the researchers’ process. No one on the John- son and Yu team appears to have experi- ence in delivering complementary therapies or working or researching inte- grative oncology practices. Notably, the Yale system includes an integrative oncol- ogy program: expertise was at hand, to which they chose not to reach out. In addition, the past president of SIO, Jun Mao, MD, who in late 2017 headed up a SIO special issue on the global movement for integrative oncology that was pub- lished in the Journal of the National Cancer Institute was a two-hour train ride away in New York City where he runs the Memo- rial Sloan Kettering integrative oncology program. Telephone and email were other communication options.

Clearly Johnson and Yu must be aware that an integrative oncology community exists. Yet neither the value of humility – to accept that those who work in the field might have expertise and thus be solicited nor the value of collegiality were apparently in play. With their experience of the media storm after their 2017 paper that focused on the killing effects of choosing alternative medicine treatments, Johnson-Yu and their team might have anticipated what was to come following this condemnation of the complementary tools of integrative medicine. They were about to publicly hang an entire field. In a more civil academic research envi- ronment, this might have been a reason to walk across campus or down the hall to get some additional perspective before filing such a judgement. Instead of civility and col- legiality, the camp of Yale researchers behaved like the personnel in different cor- ners of life in the United States. The news accounts were blasted world-wide with all the respectful decorum of a “gotcha” moment.


In an attempt to explain how 39% of US adults believe alternative medicine can cure cancer, a prominent oncologist asso- ciated with the John Wayne Cancer Insti- tute opined: “If I had to speculate, I think that there may be a skepticism of medicine and pharmaceutical industries that play a role in increasing [people’s] willingness to look at alternative therapies in spite of a lack of scientific data.”17 In the same news article on the surprising outcomes of the ASCO-Harris poll, the strategic director for pathology research at the American Cancer Society, Ted Gansler, MD added: “It’s very important to distinguish alterna- tive therapies (used instead of conven- tional treatment with the intent of treating cancer) from complementary or integra- tive therapies (used together with conven- tional treatment with the intent of relieving cancer symptoms or side effects of conventional treatment).”

It is fair to say that Johnson-Lu’s paper and the JAMA Oncology decision to publish not only muddled the ACS official’s dis- tinctions. One effect of the paper was likely to drive people further from clarity of lan- guage and common sense – what words like “alternative” and “complementary” mean. Thus they are further from the understand- ing and best treatment choices the wis- dom that Confucius has suggested begins exactly where ACS’s Gansler would have us begin, with right language. One wonders if the authors’ sowing of confusion about complementary medicine for patients and the disrespect for the integrative field may in fact contribute to such public skepticism toward regular medicine as may be behind the faulty belief in alternatives. To the extent that Johnson, Lu or other of their team members self-identify as complemen- tary and integrative medicine skeptics, this would be an ironic outcome.

I began this article sharing my biases and reactivity on approaching it. The question of intent of the authors was never far from dialogue. I asked SIO president Balneaves directly if she thought there was anti-com- plementary medicine prejudice driving this paper? Her response began generically and ended affirmatively: “Everyone comes to research with biases. We all come with cer- tain assumptions. What is important when we do our research is that we try to control them. Do I see biases in how this research was framed? The answer is yes.”

Integrative oncology, with its fundamental respect for the damage the cancer diagnosis and conventional treatment wield on body, mind and spirit, its informed rejection of unproven alternatives, and its exploration of evidence-based complementary medicine to alleviate suffering, has taken many steps toward becoming the oncology standard of care. Publication of the Johnson-Yu paper was a step backward for opening the hearts and minds of slow-to-budge practitioners and for getting the best treatment to patients at the right time. JAMA Oncology has an opportunity to declare for such a patient- centered, integrative oncology future through a proactive rejection of the multiple, mislead- ing methods and outcomes of this paper.


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