MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Cancer

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Acupuncture is a veritable panacea; it cures everything! At least this is what many of its advocates want us to believe. Does it also have a role in supportive cancer care?

Let’s find out.

This systematic review evaluated the effects of acupuncture in women with breast cancer (BC), focusing on patient-reported outcomes (PROs).

A comprehensive literature search was carried out for randomized controlled trials (RCTs) reporting PROs in BC patients with treatment-related symptoms after undergoing acupuncture for at least four weeks. Literature screening, data extraction, and risk bias assessment were independently carried out by two researchers. The authors stated that they followed the ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) guidelines.

Out of the 2, 524 identified studies, 29 studies representing 33 articles were included in this meta-analysis. The RCTs employed various acupuncture techniques with a needle, such as hand-acupuncture and electroacupuncture. Sham/placebo acupuncture, pharmacotherapy, no intervention, or usual care were the control interventions. About half of the studies lacked adequate blinding.

At the end of treatment (EOT), the acupuncture patients’ quality of life (QoL) was measured by the QLQ-C30 QoL subscale, the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), the Functional Assessment of Cancer Therapy–General/Breast (FACT-G/B), and the Menopause-Specific Quality of Life Questionnaire (MENQOL), which depicted a significant improvement. The use of acupuncture in BC patients lead to a considerable reduction in the scores of all subscales of the Brief Pain Inventory-Short Form (BPI-SF) and Visual Analog Scale (VAS) measuring pain. Moreover, patients treated with acupuncture were more likely to experience improvements in hot flashes scores, fatigue, sleep disturbance, and anxiety compared to those in the control group, while the improvements in depression were comparable across both groups. Long-term follow-up results were similar to the EOT results. Eleven RCTs did not report any information on adverse effects.

The authors concluded that current evidence suggests that acupuncture might improve BC treatment-related symptoms measured with PROs including QoL, pain, fatigue, hot flashes, sleep disturbance and anxiety. However, a number of included studies report limited amounts of certain subgroup settings, thus more rigorous, well-designed and larger RCTs are needed to confirm our results.

This review looks rigorous on the surface but has many weaknesses if one digs only a little deeper. To start with, it has no precise research question: is any type of acupuncture better than any type of control? This is not a research question that anyone can answer with just a few studies of mostly poor quality. The authors claim to follow the PRISMA guidelines, yet (as a co-author of these guidelines) I can assure you that this is not true. Many of the included studies are small and lacked blinding. The results are confusing, contradictory and not clearly reported. Many trials fail to mention adverse effects and thus violate research ethics, etc., etc.

The conclusion that acupuncture might improve BC treatment-related symptoms could be true. But does this paper convince me that acupuncture DOES improve these symptoms?

No!

The use of so-called alternative medicine (SCAM) is common among cancer patients and it may reflect the individual and societal beliefs on cancer therapy. This paper aimed to evaluate the trends of CAM use among patients with cancer between 2006 and 2018.

The researchers included 2 Cohorts of patients with cancer seen at the Oncology Department at King Abdulaziz Medical City of Ministry of National Guard Health Affairs, Riyadh, KSA, who were recruited for Cohort 1 between 2006 and 2008 and for Cohort 2 between 2016 and 2018. The study is a cross-sectional study obtaining demographic and clinical information and inquiring about the types of SCAM used, the reasons to use them and the perceived benefits. The researchers compared the changes in the patterns of SCAM use and other variables between the two cohorts.

A total of 1416 patients were included in the study, with 464 patients in Cohort 1 and 952 patients in Cohort 2. Patients in Cohort 2 used less SCAM (78.9%) than Cohort 1 (96.8%). Cohort 1 was more likely to use SCAM to treat cancer compared to Cohort 2 (84.4% vs. 73%, respectively, p < 0.0001,); while Cohort 2 used SCAM for symptom management such as pain control and improving appetite among others. Disclosure of SCAM use did not change significantly over time and remains low (31.6% in Cohort 1 and 35.7% for Cohort 2). However, physicians were more likely to express an opposing opinion against SCAM the use in Cohort 2 compared to Cohort 1 (48.7% vs. 19.1%, p < 0.001, respectively).

The authors concluded that there is a significant change in SCAM use among cancer patients over the decade, which reflects major societal and cultural changes in this population. Further studies and interventions are needed to improve the disclosure to physicians and to improve other aspects of care to these patients.

I think that these are interesting findings. Should both patients and conventional healthcare professionally truly become more sceptical about SCAM? It would be good, in my view, but can we be sure?

The answer is NO!

Firstly, we would need data from other countries (SCAM use is known to show marked national differences). Secondly, we would require more up-to-date evidence. The present paper has suggested that, within one decade, SCAM use can change. Therefore, it is only reasonable to assume that it has changed again since 2016/18.

My hope is that progress continues. And by progress, I mean that those forms of SCAM that are demonstrably useful in palliative and supportive cancer care are employed wisely, while all the many bogus alternative cancer ‘cures’ are rapidly falling by the wayside.

S0-called alternative medicine (SCAM) is often promoted for improving the quality of life (QoL) of cancer patients. Women with early-stage breast cancer often opt for trying SCAM. One such option is vitamin C. Its effectiveness in cancer treatment remains, however, unproven. On this background, this first-ever randomized clinical trial aimed to explore the effects of intravenous vitamin C (IVC) on symptoms and adverse events associated with conventional breast cancer treatment.

This single-center, parallel-group, single-blind study was conducted in the oncology ward of a tertiary care hospital in Pakistan. After informed consent, breast cancer patients with Union for International Cancer Control stages IIA to IIIb were included in the study. Three hundred and fifty patients were randomized into two groups at a ratio of 1:1. The study group received 25 grams per week of IVC at a rate of 15 grams per hour for four weeks in addition to their current standard treatment, and the control group received a placebo in addition to their current standard treatment.

In patients who had received IVC, there were significant decreases in the severity scores after 28 days for the following symptoms:

  • nausea, loss of appetite (2.26 ± 0.51 vs. 2.11 ± 0.52; p-value: 0.007),
  • tumor pain (2.22 ± 0.45 vs. 1.99 ± 0.40, p-value: <0.0001),
  • fatigue (3.11 ± 0.32 vs. 2.87 ± 0.29; p-value: <0.0001),
  • insomnia (2.59 ± 0.35 vs. 2.32 ± 0.36, p-value: <0.0001).

The authors concluded that this study shows an improvement in the mean severity score of nausea, fatigue, tumor pain, loss of appetite, and fatigue. More studies are also needed to assess the long-term effects of IVC in the cancer management. This shall help incorporate the use of IVC in standard practice to make the journey of cancer management comfortable for the patients.

This new study does not stand alone. A 2014 review summarised three prospective studies as well as case reports and retrospective studies concluding that intravenous (IV) vitamin C alleviates a number of cancer- and chemotherapy-related symptoms, such as fatigue, insomnia, loss of appetite, nausea, and pain. Improvements in physical, role, cognitive, emotional, and social functioning, as well as an improvement in overall health, were also observed.

What about the mechanism of action? The authors of the new study offer the following explanation:

The role of vitamin C in reducing symptoms in cancer patients can be explained by its antioxidant properties. It is known that radiation and chemotherapy along with tumor cell metabolism increase oxidative stress in cancer patients. This stress is combated by the intrinsic antioxidants of the body including vitamin C. It is seen that patients with cancer have low levels of vitamin C in their bodies. This is because uncontrolled oxidative stress in cancer leads to high consumption of intrinsic body reserves resulting in vitamin C depletion. If not replenished duly, this deficiency eventually leads to the unopposed production of reactive oxygen species (ROS). The gut mucosa and the neural tissues, being the most sensitive to ROS, are affected the most. This leads to mucosal irritation of the gastrointestinal tract causing symptoms of nausea, vomiting, and loss of appetite. The neural irritation may trigger mental disorders including insomnia, tumor pain, and fatigue. Thus, replenishment of the intrinsic reserve by parenteral vitamin C administration may help combat the unopposed ROS production and play a vital role in alleviating cancer symptomatology, and hence QoL in these patients, as witnessed in our current study.

This explanation may be somewhat simplistic; moreover, the new study is far from flawless, and the totality of the evidence seems less than compelling. Nonetheless, the subject is, in my view, interesting and would seem to deserve further rigorous study.

According to one website, electromagnetic fields (EMFs) are “the new smoking“:

For decades, a group of cigarette companies referred to as ‘Big Tobacco’ financed bogus scientific studies claiming smoking was perfectly safe. This tricked doctors, scientists, politicians, and smokers into a false sense of security. There were early warning signs that smoking was dangerous, but it took 50 years for the government to finally take action. Today we’re facing an even bigger health threat… EMFs. Even if many doctors, politicians and Big Wireless still claim that EMFs are perfectly safe, the early warning signs could not be clearer:

  • Many leading EMF scientists say EMFs should be classified as a “Class 1” definite carcinogen (just like smoking and asbestos)
  • The best functional medicine doctors like Dr. Dietrich Klinghardt, MD, PhD have observed that EMFs are at the very root cause of “Mystery” symptoms including insomnia, fatigue, depression, and digestive issues.
  • New technologies like the “5G” (fifth generation) networks are being rolled out at a frantic pace, while exactly ZERO biological studies prove their safety.
  • EMF “safety” standards haven’t been updated since 1996, and are based on short-term exposure to ONE device.

The Atox Bio Computer is one of many devices marketed as the solution. It is a little device that supposedly protects any person who is gullible enough to buy it from electrosmog and other EMFs. It was developed by the Russian physicist, Alexander Tarasov. Worn around the neck, the device allegedly acts by “converting negative information into positive”. Alarmingly, the Atox is also promoted as protection against ionizing radiation. Pseudo-scientific explanations are given for the mode of action, in which there is talk of an ominous “energy-information component” of radiation:

“The revolutionary insight of Dr. Tarasov is that any electromagnetic radiation of any origin consists of two components, the physical and the energy-information component. Whereby the energy-information component precedes the physical vibration and primarily affects the human organism or its bioenergetic field.”

Sounds weird? Yes, I agree! But it must be true because it is supported by a real professor from a leading medical school. In 2007, it was reported in a press release that Prof. Dr. Michael FRASS examined the ATOX Bio Computer and found that 90% of people with too low and 100% with too high initial values achieved normalization of their vegetative performance. Altogether, 92.9% of the persons benefited by wearing the ATOX biocomputer.

With regard to the ratio of sympathetic to parasympathetic impulses, 100% of the people with too low and 82.3% with too high initial values normalize their range of the total autonomic power. Overall, 84.2% of the treated individuals showed a positive course under the influence of ATOX biocomputer. According to Frass, this means that people with a high stress factor have a very high probability of returning to normal values of the autonomic system with the help of the ATOX biocomputer.

Considering the fact that such findings, if true, would necessitate to re-write large parts of the textbooks of physics and medicine, it is surprising that Frass does not include them in his CV. Perhaps he is a deeply modest scientist? Or maybe he does not want to spoil his chances for a Nobel?

Prof. Frass has, of course, featured on this blog before. For instance, because his many studies of homeopathy are invariably positive, or because his results have been shown to contain a few (pro-homeopathy) ‘errors’, or (most recently) because he published a trial of homeopathy that claimed lung cancer patients live longer if they are treated with homeopathy. The latter study is now under investigation for fraud.

Had such an investigation been initiated in back 2007 when Frass came out with his ATOX Bio Computer study (which incidentally was never properly published [at least I could not find it on Medline]), we would now not need to worry whether some desperate cancer patients did take Frass’ ‘science’ seriously.

An article in the Daily Mail (I know, not my favorite newspaper either) reported about a UK court case against the father of an 11-year-old daughter who objected to her being given conventional life-saving treatments for her leukemia. The man was said to be worried about possible side effects and wanted to explore homeopathic and natural therapies, while his estranged wife favored the conventional approach.

Mr Justice Hayden decided that there is ‘no basis’ for the man’s homeopathic option and that specialists can lawfully carry out the conventional treatments. But the father said he believed that previous chemotherapy had already weakened his daughter’s immune system and that the conventional treatment proposed has further side effects. He, therefore, wanted to try homeopathic and natural therapies, including ozone therapy. ‘I am not waiting for her to deteriorate and get worse,’ he told the judge. ‘Chemotherapy is not the only way. There are so many other different therapies I am hoping to try – anything as long as it doesn’t really affect her.’

A specialist treating the girl told the judge that the treatments proposed are the best option and that they know of no homeopathic options which would help. Mr Justice Hayden approved Great Ormond Street’s plan and said doctors should start the treatments as soon as possible. ‘If she receives no treatment then her life expectancy is weeks,’ he said. ‘There is no basis for the father’s homeopathic option.’

This case highlights the indirect risks of homeopathy and similar treatments in an exemplary fashion. The therapies per se might be harmless but the therapists are clearly not. There are enough homeopaths who are deluded enough to persuade their patients that homeopathy can alter the natural history of even serious conditions such as cancer. And, as we have discussed recently, these irresponsible fools are not just from the ranks of the lay-homeopaths (homeopaths who have not been to medical school) who might not know better; they also include medically trained homeopaths and even professors at leading medical schools.

 

Qigong can be described as a mind-body-spirit practice that improves one’s mental and physical health by integrating posture, movement, breathing technique, self-massage, sound, and focused intent. But does it really improve health?

The purpose of this review was to evaluate the effectiveness of Qigong in improving the quality of life and relieving fatigue, sleep disturbance, and cancer-related emotional disturbances (distress, depression, and anxiety) in women with breast cancer.

The PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Sinomed, Wanfang, VIP, and China National Knowledge Infrastructure databases were searched from their inceptions to March 2020 for controlled clinical trials. Two reviewers selected relevant trials that assessed the benefit of Qigong for breast cancer patients independently. A methodological quality assessment was conducted according to the criteria of the 12 Cochrane Back Review Group for risk of bias independently. A meta-analysis was performed using Review Manager 5.3.

A total of 17 trials were found in which 1236 cases were enrolled. The quality of the included trials was generally low, as only 5 of them were rated high quality. 14 studies were conducted in China. The types of qigong included Baduanjin Qigong (9 trials), Chan-Chuang Qigong (1 trial), Goulin New Qigong (2 Trials), Tai Chi Qigong (2 Trials), and Kuala Lumpur Qigong (1 trial). The course of qigong ranged from 21 days to more than 6 months. Four trials compared qigong to no treatment, one sham Qigong, seven compared to other types of exercise, and 6 to usual care.

The results showed significant positive effects of Qigong on quality of life (n = 950, standardized mean difference (SMD), 0.65, 95 % confidence interval (CI) 0.23–1.08, P =  0.002). Depression (n = 540, SMD = −0.32, 95 % CI −0.59 to −0.04, P =  0.02) and anxiety (n = 439, SMD = −0.71, 95 % CI −1.32 to −0.10, P =  0.02) were also significantly relieved in the Qigong group. There was no significant benefit on fatigue (n = 401, SMD = −0.32, 95 % CI  0.71 to 0.07, P = 0.11) or sleep disturbance relief compared to that observed in the control group (n = 298, SMD = −0.11, 95 % CI  0.74 to 0.52, P = 0.73).

The authors concluded that this review shows that Qigong is beneficial for improving quality of life and relieving depression and anxiety; thus, Qigong should be encouraged in women with breast cancer.

No, this review does not show that Qigong is beneficial for improving quality of life and relieving depression and anxiety!

Why?

  1. Most primary studies were of very poor quality.
  2. Most were from China, and we know (and have often discussed) that such trials are most unreliable.
  3. No trial even attempted to control for placebo effects.

A better conclusion would therefore be something like this:

Even though most trials conclude positively, the value of Qigong can, for a range of reasons, not be determined on the basis of the evidence available to date.

On 7/10/2020, I discussed a study suggesting that homeopathy improves the quality of life and survival of cancer patients. Now, these data have been carefully scrutinized by a group of members of the „INH“ and „Initiative für Wissenschaftliche Medizin“.

By guest bloggers Norbert Aust and Viktor Weisshäupl

Abstract

The first impression of the results of the study on the adjunctive homeopathic treatment of patients with non-small cell lung cancer (NSCLC) is that of a seemingly rigorous trial with valid results. But a more thorough review yields different insights:

  • The methods and definitions were pre-determined in a protocol and seem to have been maintained up to the end. But the date given in the document pointing at some point in time before enrollment began is wrong and misleading: This protocol was first published by uploading it to the register only two months after data assessment was completed with outcomes presumably available.
  • The data initially saved to the register are not in agreement with the information given in the published paper: important definitions were subjected to considerable modifications while the study was underway. None of these modifications are mentioned in the paper, neither a rationale nor a comment of their impact on the results was provided.
  • Some of the modifications with presumably heavy impact on the results were introduced with the upload of the protocol only, that is two months after data collection was completed. These were (a) a massive extension of the exclusion criteria: the number increased from 1 during initial registration to 20 in the final paper. and (b) an equally massive reduction of the follow-up time for the primary endpoint from two years to 18 weeks.
  • The paper discloses no reason why the additional exclusion criteria were introduced. Their selection seems arbitrary without any apparent necessity arising from the trial itself.
  • The patients who did not meet the added criteria and were thus excluded are not mentioned in the publication. The CONSORT flow chart does not give information either of their number or of the point in time when they were excluded.
  • The survival curves of the placebo and verum groups show some aspects that arise if the inter-group difference was due to the exclusion of unfavorable data.
  • It is hard to imagine that, in this trial, the homeopathic preparations had strong effects on the patients’ health, while other rigorous studies or systematic reviews failed to notice such effects.

Altogether, it seems much more plausible to assume that the positive results were achieved by post hoc data manipulation, namely by omitting patients with unfavorable outcomes, than by rigorous and valid science. A retraction of the paper seems the only appropriate measure to avoid misleading the public. 

Introduction

Due to its outstanding results, the study about adjunct homeopathic treatment of non-small cell lung cancer patients was met among homeopaths with enthusiasm. However, in this article, we will show that the enthusiasm is unjustified because the results may not be based on a rigorous trial meeting established scientific criteria. Crucial definitions were modified, while the study was underway or even after data collection was completed. It stands to reason that this introduced bias in favor of homeopathy.

For this analysis, we considered the following sources of information :

  • the text of the published paper (link)
  • the data that were uploaded during registration (link)
  • the history of changes of the registered data (link)
  • the study protocol included in the registration (link)

As all of this information is readily available on the internet, it is easy to double-check our findings and verify our statements. We also submitted a letter to the editor of the Oncologist, the journal where the paper was published which has not yet been published (status 06-06-2021).

The study

At first glance, the study meets the requirements for reliable evidence.

  • There is a study protocol dated January 11, 2011, well before recruiting of participants started. It provides definitions that were used until the end.
  • The study was registered at ClinicalTrials.gov before recruiting started.
  • The methods of randomization and blinding are suitable to meet the requirements for a low risk of bias rating.
  • The presentation of the paper follows the principles set out in the CONSORT-Statement.
  • The paper was published in a peer-reviewed journal of some reputation.

The study yielded formidable results in favor of homeopathy: In the group that received the adjunctive homeopathic treatment, the quality of life improved continuously throughout the follow-up time, while the patients in the placebo group deteriorated. In addition, the median survival time was only about two-thirds compared to the patients in the homeopathy group. However, the impression of a valid study does not stand up to closer scrutiny when the history of changes is taken into account.

Changes in study parameters 

Between the initial registration and data upload in January 2012 (Link), shortly before recruiting started in February 2012, and the publication in October 2020, multiple changes in essential study parameters occurred:

Registration January 2012 Publication October 2020
Number of participants 600 150
Number of study arms 2 3
Number of exclusion criteria 1 20
Follow-up time for Quality of life 104 weeks (*) 18 weeks
Number of cancer types 3 1
(*) Derived from “Time Frame: 7 Years” minus the recruitment period of 5 years.

Note the drastic reduction in the follow-up time for quality of life by more than 80 % which was defined as the primary endpoint. Furthermore, note the substantial increase in the number of exclusion criteria. Both issues will be discussed in more detail below.

In contrast to the requirements for a rigorous and valid trial, these modifications are not mentioned in the published paper, and no rationale is given as to why they became necessary. As a consequence, the authors do not discuss the possible impact these modifications may have had on the results.

The study protocol 

A study protocol is available in the registration database. It was first uploaded on September 18, 2019, about two months after the end of data collection in July 2019 (Link). The document itself is dated January 11, 2011, which would place it about a year before the study was registered. However, this date is obviously wrong: there are substantial discrepancies between the parameters specified in the protocol and the data provided one year later during initial registration:

Protocol, allegedly January 2011 Registration January 2012
Number of participants 300 600
Number of study arms 3 2
Number of exclusion criteria 9 1
Follow-up time for Quality of life 18 weeks 104 weeks (*)
Number of cancer types 1 3
(*) Derived from “Time Frame: 7 Years” minus the recruitment period of 5 years.

We see no sensible explanation why the parameters given in the study protocol allegedly compiled in January 2011 are in line with the publication nine years later, but not with the registration only one year after the protocol was compiled. The only sensible conclusion seems to be that this protocol was not completed on the date indicated, but at a much later point in time, maybe just shortly before its upload (September 2019). This impression is corroborated by the information presented in the document that was not available on the date given: On page 10 the software package used in data analysis is referenced as “IBM SPSS statistics 25.0” while, at the beginning of 2011, when the protocol was allegedly compiled, the current version number of this package was 19 only.

A second clue: Also on page 10 there is a reference “(EORTC-QLQ-C30 remaining dimensions; SF-36; subjective well-being)25.” with the number 25 indicating some reference. And some references that is, but not in the protocol – this does not have any references – but in the published paper, where the 25 indicates a paper on the SF-36 questionnaire. So it stands to reason that the number in the protocol originates from some messed up copy and paste procedure from the draft of the paper. Which would indicate that the paper and the protocol were at least partially developed in parallel.

It seems therefore reasonable to assume, that the protocol was finished only shortly before it being uploaded in September 2019, that is two months after data collection was completed.

However, the obviously inaccurate date given in the protocol supports the impression that the study parameters were set a year before the study began and were consistently maintained during the course of the trial, which is not the case, as the above tables show.

Change in exclusion criteria 

The initial registration data list pregnancy as the only exclusion criterion. But with the upload of the protocol, which took place two months after data collection was completed, the number of exclusion criteria was increased to nine, only to be enlarged once again in the final publication to the final number of twenty. It is beyond any doubt that at least the final increase of eleven criteria took place after the data collected from the patients were available. But all this is neither disclosed in the final paper nor is there any rationale given for this action.

The patients excluded by the additional criteria never appear anywhere, they are not included in the CONSORT-flow-chart, Fig 3 in the study. It is obvious that some patients were excluded: What was the reason to define such an abundance of criteria, if they were not to be applied? As a consequence, the CONSORT diagram seems to be incomplete which would be in violation of the CONSORT statement.

Thus, an unknown number of patients seems to have been excluded from the study by criteria defined at a time after data collection was completed with outcomes available. After all, eleven of the exclusion criteria were established even after the protocol had been uploaded, at least those were established well after the patients’ results were available.

This raises the question of why these exclusion criteria were introduced. One would assume that an intervention to treat stage III and stage IV lung cancer patients should be effective under the conditions that are usually present in such patients. One would expect that patients somewhat advanced in age, like in this study, usually suffer from some health problems, regardless of their cancer condition. What is the sense of excluding patients with hematological, hepatic, or renal pathology, with coronary heart disease or rheumatism? Homeopathy is claimed to be able to treat comorbidities based on the assessment of symptoms independent of what disease they belong to. And this apparently was the idea at the start of the trial where only pregnancy was specified as an exclusion criterion, while it was understood that elderly patients to be enrolled in the study would suffer from some additional medical problems.

On the other hand, not all health conditions that are associated with advanced age were excluded. Diabetes, hypertension, gastrointestinal diseases, or COPD were no reason to exclude any patient from participation. Only very few of the criteria are somewhat self-explanatory as to why they were defined as exclusion criteria, e.g. if a patient was unwilling to give her informed consent.

Altogether, the assumption seems reasonable that more patients had participated in the trial than accounted for in the publication, and that an unknown number of them were excluded according to criteria that were not present until after data collection was completed. If so, a substantial bias was introduced.

Median survival time

Here, we will focus on the comparison between the homeopathy and placebo groups and leave aside the third group not receiving any additional treatment at all.

If the favorable result in survival really was established by dropping unfavorable data, this might be recognized in some characteristics of the survival curves. Therefore, we modeled this situation starting with two random distributions somewhat tweaked to resemble the typical shape of natural survival functions.

This graph shows the two distributions (n = 80) defined in the range of 0 to 200 as thin lines. Both are very similar to each other with median survival at 27 weeks. If 15 of the 20 patients with the shortest survival are dropped from the thin blue line this would result in the solid blue line (“Hom”). If, on the other hand, 15 out of 20 patients with the longest survival are dropped from the other distribution this would yield the solid red line (“Plac”).

The new functions show some characteristic properties:

  • In the red line, median survival drops by 8 weeks to 19 weeks.
  • In the blue line median survival rises by 12 Weeks to 39 weeks.
  • The difference between the two functions arises from of the first 12 weeks alone. With the blue line, 8 people died, with the red line 23 people died during the first 12 weeks. After week 12 up to week 80, the same number of fatalities occur in both groups (blue: 36, red: 37).

After week 80, the two functions start to converge, which is due to the fact that at some future point all the patients of both groups will be dead. The survival functions that are reported in the study show the same characteristics.

Assuming that homeopathy did not have any effect, both groups should show more or less identical survival functions. In the paper 10.1 months = 303 days is cited from literature as to be expected under conventional care, maybe with some margin to the better because the data that yielded this value of 10.1 months were more than six years old at the time of the trial. The survival functions allegedly found in the trial show:

  • Median survival time with the placebo group is reduced by 46 days compared to conventional care alone.
  • Median survival time with the homeopathy group is increased by 132 days compared to conventional care alone.
  • The advantage of homeopathy arises within the first 9 weeks alone, where only two patients died (out of 51) in the homeopathy group compared to 11 (out of 47) in the placebo group. After this initial phase, the groups developed in parallel: By the end of the two-year follow-up time an additional 26 patients died with homeopathy, and about the same, namely 25 patients died with placebo.

The inevitable convergence of both functions apparently started outside the two-year follow-up. In other words, the survival functions given in the study for placebo and homeopathy treatments show characteristics that match what you would be expected, if two very similar functions were manipulated by dropping unwanted results, i.e. “good” survival data from placebo and “bad” survival data from homeopathy functions. After week 9, the two functions develop parallel to each other, indicating a lack of effect of homeopathy even though the treatment continued until the death of the patient or the end of the study. However, with ongoing effective treatment, the functions should continue to diverge. It seems implausible that homeopathy should be effective on a short time basis only, with a sudden complete loss of effectiveness later on.

Reduction of observation time

Quality of life was defined as the primary endpoint. On initial registration, it was specified that patients should be observed for the entire seven-year duration of the study which, allowing for the recruitment period of five years, results in a follow-up time of two years or 104 weeks for each individual patient. According to the information provided in the study, this was indeed done: “Patients were followed up every nine weeks until death” (or until the end of the study, of course), and questionnaires were completed to determine the quality of life.

The reduction of follow-up time from 104 to 18 weeks was first introduced when the protocol was uploaded. So it is obvious that this substantial reduction occurred after data collection was completed and that data from more than 80 % of the originally defined follow-up were omitted.

Incomplete outcome reporting, especially when a larger scope was defined at the beginning of the study, is considered a source of substantial bias and a major shortcoming in clinical trials: Maybe patients initially experienced an improvement in their quality of life due to whatever effect – but what were the results after this initial phase? Why were they omitted? Perhaps because they got worse than in the placebo group? The long-term development would have been a vital aspect for the evaluation of efficacy – and the study originally was designed to evaluate such long-term effects. Yet, the authors’ conclusions on the quality of life – notably: the primary outcome criterion – are based on less than 20 % of the follow-up in which a positive effect may have occurred due to bias or by chance. To extrapolate from this short time to the total period is not justified and may be misleading. A detailed review of the quality of life results is meaningless: they do not disclose any long-term effects and they are subject to bias caused by the post hoc exclusion of patients anyway.

Study results

The overall evidence on the effectiveness of homeopathy is not encouraging. The quintessence of all systematic reviews that have looked at homeopathy as a whole is that some marginal effect may be found, if all studies are included in the review, regardless of their quality. But this result is questionable due to the generally low quality of the primary studies (Link, in German). However, when quality is taken into account, the systematic reviews do not produce robust evidence for any positive effect beyond placebo. In addition, no review could identify a single condition in which homeopathy is of well-established therapeutic benefit.

This study on NSCLC contradicts the long-established and often-confirmed evidence. During the follow-up time for the patients who actually received the prescribed homeopathic preparations, the quality of life improved steadily in all subscales – even down to the patients’ financial situation – whereas the opposite was observed in the placebo patients. In addition, the mean survival time was about two-thirds longer for the homeopathy patients than for the placebo group.

After 200 years of clinical research into homeopathy, it seems unlikely that such a powerful effect of homeopathy should not have been noticed before. Another scenario seems to be much more plausible:

  • The survival times of the placebo group were worse than the data from the literature. This could be due to the fact that patients with relatively good outcomes were excluded by the introduction of additional exclusion criteria.
  • The survival times of the homeopathy group were considerably better than expected. This could also be due to the additional exclusion criteria, in that patients with poor outcomes were excluded retrospectively.
  • The long time frame where the survival functions run in parallel from week 9 onwards until the end of the two years observation period indicates the lack of effect of the homeopathic treatment. The advantage occurring in the first nine weeks alone seems to be the result of unwanted data being dropped.
  • In the case of quality of life (after all, not a “hard” criterion, but based on information from the patients ), the advantage in survival would have initially created a positive effect for the homeopathy group. Then, reporting was discontinued, once the initial positive effects presumably caused by the selective omission of patients had ended.

In conclusion, it seems likely that the substantial modifications of crucial study parameters that occurred after the study had been started and results had become available biased the results in favor of homeopathy. Therefore, this study does not meet strict scientific standards that were established to exclude any confounding factors or biases. If our analysis is correct, the results of this study are invalid, and the authors’ conclusions are not justified. Retraction of this study seems to be appropriate.

Reference

[1] Frass M, Lechleitner P, Gründling C et al. Homeopathic Treatment as an Add-On Therapy May Improve Quality of Life and Prolong Survival in Patients with Non-Small Cell Lung Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blind, Three-Arm, Multicenter Study. The Oncologist 2020;25:e1930–e1955 https://theoncologist.onlinelibrary.wiley.com/doi/epdf/10.1002/onco.13548

The integration of so-called alternative medicine (SCAM) into cancer care may reduce the adverse effects of anti-neoplastic treatment but also cause new problems and non-adherence to conventional treatment. Therefore, its net benefit is questionable.

The aim of this randomized controlled study was to investigate the impact of integrative open dialogue about SCAM  on cancer patients’ health and quality of life (QoL).

Patients undergoing curative or palliative anti-neoplastic treatment were randomly assigned to standard care (SC) plus SCAM or SC alone. A nurse specialist facilitated SCAM in one or two sessions. The primary endpoint was the
frequency of grade 3–4 adverse events (AE) eight weeks after enrollment. Secondary endpoints were the frequency of grade 1–4 AE and patient-reported QoL, psychological distress, perceived information, attitude towards and use of SCAM 12 and 24 weeks after enrollment. Survival was analyzed post-hoc.

Fifty-seven patients were randomized to SCAM and 55 to SC.  No significant differences were found in terms of AEs of cancer patients. A trend towards better QoL, improved survival, and a lower level of anxiety was found in the SCAM group.

The authors concluded that integration of SCAM into daily oncology care is feasible. IOD-CAM was not superior to SC in reducing the frequency of grade 3-4 AEs, but it did not compromise patient safety.  Implementation of  SCAM
may improve the QoL, anxiety, and emotional well-being of the patients by reducing the level of nausea, vomiting and diarrhea. Finally, SCAM potentially improves the patients’ self-care, which contributes to
increased treatment adherence and improved survival.

This is an interesting paper with a very odd conclusion. The positive trends found failed to be statistically significant. Why employ statistics only to ignore them in our interpretation of the findings?

I can well imagine that the integration of effective treatments into cancer care improves the outcome. I have no problem with this at all – except it is not called INTEGRATIVE MEDICINE but EVIDENCE-BASED MEDICINE!!! If we integrate dubious treatments into cancer care, it’s called INTEGRATIVE MEDICINE, and it’s unlikely to do any good.

In my view, this small study showed just one thing:

Integrative medicine does not reduce adverse effects in cancer patients.

 

Due to polypharmacy and the rising popularity of so-called alternative medicines (SCAM), oncology patients are particularly at risk of drug-drug interactions (DDI) or herb-drug interactions (HDI). The aims of this study were to assess DDI and HDI in outpatients taking oral anticancer drugs.

All prescribed and non-prescribed medications, including SCAMs, were prospectively collected by hospital pharmacists during a structured interview with the patient. DDI and HDI were analyzed using four interaction software programs: Thériaque®, Drugs.com®, Hédrine, and Memorial Sloan Kettering Cancer Center (MSKCC) database. All detected interactions were characterized by severity, risk, and action mechanism. The need for pharmaceutical intervention to modify drug use was determined on a case-by-case basis.

A total of 294 patients were included, with a mean age of 67 years [55-79]. The median number of chronic drugs per patient was 8 [1-29] and 55% of patients used at least one SCAM. At least 1 interaction was found for 267 patients (90.8%): 263 (89.4%) with DDI, 68 (23.1%) with HDI, and 64 (21.7%) with both DDI and HDI. Only 13% of the DDI were found in Thériaque® and Drugs.com® databases, and 125 (2.5%) were reported with a similar level of risk on both databases. 104 HDI were identified with only 9.5% of the interactions found in both databases. 103 pharmaceutical interventions were performed, involving 61 patients (20.7%).

The authors concluded that potentially clinically relevant drug interactions were frequently identified in this study, showing that several databases and structured screening are required to detect more interactions and optimize medication safety.

These data imply that DDIs are more frequent than HDIs. This does, however, not tell us which are more important. One crucial difference between DDIs and HDIs is that the former are usually known to the oncology team who should thus be able to prevent them or deal with them appropriately; in contrast, HDIs are often not known to the oncology team because many patients fail to disclose the fact that they take herbal remedies. Some forget, some do not think of herbals as medicine, others may be worried about their physician’s reaction.

It follows that firstly, conventional healthcare practitioners should always ask about the usage of herbal remedies, and secondly, they need to be informed about which herbal remedy might interact with which drug. The first can easily be implemented into routine history-taking; the second is more problematic, not least because our knowledge about HDIs is still woefully incomplete. In view of this, it might often be wise to tell patients to stop taking herbal remedies while they are on prescription drugs.

By guest blogger João Júlio Cerqueira

A word of caution to all the skeptics out there defending Reason, Science, and the Truth. This is a summary of a long story and only about one of many battles. It is not a very beautiful story but it is what it is. I’m a medical doctor, influenced by some of the great minds of our time, all of them familiar to you, Edzard Ernst, Steven Novella, David Gorski, Harriet Hall, Kimball Atwood and so much more (thank you all, for everything that you do).

I started reading skeptic blogs in 2013 and was amazed by the lack of critical thinking about science production and the lack of knowledge about pseudoscience in the medical community. And if this was bad in the medical community, in the general population it should be close to apocalyptic…

In 2017, I was confronted by a medical doctor that imported the great pitches of international charlatans. From alkaline diet, bioidentical hormones, colonic cleansings all through the “health benefits” of drinking diluted saltwater…yes, this is a real thing. He was transformed into a television celebrity, wrote one of the bestselling books in my country, and only a few people were horrified by what was happening. How? How can someone that says that kind of stuff could have this kind of reach in the media? He even sold foot detox!

So, frustrated by the lack of action of the regulatory institutions and the lack of critical approach by the media, I decided to create a blog that I called SCIMED. Using what I had learned through the years with “the masters of skepticism”, I tried to teach and convince people why pseudoscience is useless and dangerous. Why those selling pseudoscience are a danger to society and are only after the wallet of scientifically illiterate people.

Thanks to hard work and a lot of luck, the blog started to have a decent public projection. Started to get invitations to interviews in the media, invited to speak at conferences, started to write in the opinion section of mainstream journals, appearing on television, invited to do a TEDx talk, was invited to be one of the subscribers to the first world manifesto against pseudoscience and even had the pleasure to be a speaker in a conference side by side with Edzard Ernst, one of my heroes!

It was like something was changing. Well, it was not.

With public projection, came the problems…people calling my employers to get me fired, physical and death threats, constant harassment by email or in social media, doxing, and false accusations about my personal and professional life. You name it. And I endured…I considered it the dark side of defending Science and Truth.

In April of 2019, I was invited to represent my country´s Medical College in a debate about pseudoscience on television, prime time. I was very excited and emotion clouded my reason. I didn´t think about the consequences. And well, it was a shitshow.

The audience was dominated by alternative health practitioners. The moderator was sympathetic with alternative health practices. And of course, the people representing the alternative health practitioners didn’t play by the same rules. They used deception, lying, testimonials, and all the logical fallacies you can think of.

But what really took me over the hedge was a Traditional Chinese Medicine Practitioner with connections to the Chinese Government, a constant presence in the mainstream media, that started to sell “acupuncture anesthesia” as something valid. Talking about how he, more than 20 years ago, used this practice to help perform surgical procedures. For me, that was a disrespect for all the people that suffered at the hands of Mao´s Chinese dictatorship. All the people that suffered excruciating pain, being operated on without general anesthesia only to sell East Snake Oil to the West. The “miracle” of acupuncture and Eastern medicine. The propaganda.

We exchanged words in the debate and that continued into social media. In the days after, I was called everything you can imagine by the defenders of alternative therapies. And this man took the opportunity to write that I was “short, ugly and bald” and that I have an “inferiority complex” because of that. That I´m a lousy doctor that cannot compete with his clinics. That only a masochist woman would want something with me.

But I endured. I could not stop feeling disgusted by the lack of shame of these people. I could not let go. Like Gaad Sad, I feel physical pain when someone is bullshitting. It makes me physically sick that people can say outrageous things with a serious face.

So, I wrote a blog post to explain the myth and the horror of acupuncture anesthesia and to dismantle other claims said by that man, like “all babies born with fire in the

liver…if you treat that problem, you can prevent infertility and cancer metastasis in the future!”. Preventing metastasis of a non-existing cancer… And I used a lot of adjectives: dumb, ignorant, charlatan, and snake oil salesman.

In November of 2019, this man goes to a wannabe Joe Rogan show and tells all sort of outrageous things like “Chinese people are so many because Traditional Chinese Medicine was very advanced for those days” or “until recently Traditional Chinese Medicine was more effective treating cancer than Conventional Medicine” or “Homeopathy works but they don´t want you to know…see this Documentary”. Again, I used sarcasm, irony, and a lot of adjectives.

And then, legal problems…

Soon after I wrote this last blog post, I received a letter from the court saying that I was being sued by this man. I hired a lawyer and made a lengthy response to all the accusations, more than 100 pages. Nevertheless, I have been charged with seventeen defamation crimes, awaiting trial, for defending the truth. For defending the people that Institutions refused to defend.

My country, Portugal, legally recognizes “Non-Conventional Therapies” like Homeopathy, Acupuncture, Traditional Chinese Medicine, Osteopathy, Chiropractic, and Naturopathy. My country, instead of defending the consumer, took the option to give these people the legal right of robbing people. I thought that the COVID-19 pandemic would change that a little bit since pseudoscience contributed zero for solving the problem, alternative practitioners embraced negationism about COVID-19, and Traditional Chinese Medicine was put in the corner. It was Science that came to the rescue with vaccines.

But now, when the pandemic is finally getting managed in my country, the snakes are starting to come out of hibernation to sell snake oil. And the media are giving them credit, again, like nothing has happened…nothing has changed, except for me.

Right now, I face four legal battles, for defamation. Besides this man, I have another lawsuit from a Nurse that promotes Reiki and Traditional Chinese Medicine, other from a Naturopath/Quantum Doctor and, lastly, from a Medical Doctor that was the head of the “Doctors For the Truth”, an organization part of an international network of Health Professionals that still denies the science about COVID-19.

So, this is my prize for all the hours battling liars and charlatans. The regulatory institutions don´t care. The mainstream media and Social Media don´t care. They are like brokers. They always win no matter if the stock market goes up or down. They will use you just to fuel the battle between science and pseudoscience and make money out of it. Why do you think the “Disinformation Dozen” still exists, besides some gestures of goodwill by the Social Media giants?

What I learned and you should learn…

I learned that it is pointless trying to convince people to change their minds on social media… People don´t follow reason, follow emotion, and something closer to religious belief. People want to be right, don´t want to learn what is right. Facts don´t change the minds of believers.

I learned that “True Skeptics” are unicorns. Everyone is a rational, skeptical person that values truth, reason, and science until you hit some nerve, some irrational belief that they hold dear. And then the “skepticism” goes down the drain. The more topics you talk about, the lonely you will be. And then you became a unicorn or, in the words of Malcolm Gladwell in the book “Talking to Strangers”, a Holy Fool: the truth-teller that is an outcast.

The COVID-19 pandemic just made things a lot worse…People started to getting hit by the pandemic in their quality of life and you start seeing hardcore skeptics doubting the most basic science and common sense. You even see some of your personal heroes like John Ioannidis going down the rabbit hole. Making the same basic mistakes that he spent his life point out about science production!

You start to see the animal inside us taking ground, what William James argued: if something improves your chances of survival, is not that the “truth”? The pragmatic, utilitarian truth? We saw irrationality in all its splendor, people negating reality, trying to conserve their way of life, making sense of events they don´t control. Fighting for control. Reason went to sleep and a lot of skeptics ceased to be…

So, I came to ask for your help… After two years of enduring the Sword of Damocles over my head, the energy to continue is running out. The SLAPP (Strategic lawsuit against public participation) they call it, is making a dent in my will to continue to fight against irrationality and charlatans.

So, I came to ask for your help, the International Skeptic community, for covering the legal expenses. I already asked for the support of my country’s skeptical community but it was not enough…only after two years of this marathon probably will take another two, I took this decision. I´m not proud of this, I´m angry that these people, besides robbing the sick and fragile giving them false hope are now making those who fight them spend money and probably pay “compensation” for not be silent about charlatanism. You can support me through Paypal or Patreon. Thank you in advance and I will keep you up-to-date.

PS

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