alternative medicine
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.
This study describes the use of so-called alternative medicine (SCAM) among older adults who report being hampered in daily activities due to musculoskeletal pain. Cross-sectional European Social Survey (EES) Round 7 (2014) data from 21 countries were examined for participants aged 55 years and older, who reported musculoskeletal pain that hampered daily activities in the past 12months. From a total of 35,063 individuals who took part in the ESS study, 13,016 (37%) were aged 55 or older; of which 8183 (63%) reported the presence of pain, with a further 4950 (38%) reporting that this pain hampered their daily activities in any way.
Of the 4950 older adult participants reporting musculoskeletal pain that hampered daily activities, the majority (63.5%) were from the West of Europe, reported secondary education or less (78.2%), and reported at least one other health-related problem (74.6%). In total, 1657 (33.5%) reported using at least one SCAM treatment in the previous year. Manual body-based therapies (MBBTs) were most used, including massage therapy (17.9%) and osteopathy (7.0%). Alternative medicinal systems (AMSs) were also popular with 6.5% using homeopathy and 5.3% reporting herbal treatments. A general trend of higher SCAM use in younger participants was noted.
SCAM usage was associated with
- physiotherapy use,
- female gender,
- higher levels of education,
- being in employment,
- living in West Europe
- having multiple health problems.
The authors concluded that a third of older Europeans with musculoskeletal pain report SCAM use in the previous
12 months. Certain subgroups with higher rates of SCAM use could be identified. Clinicians should comprehensively and routinely assess SCAM use among older adults with musculoskeletal pain.
Such studies have the advantage of large sample sizes, and therefore one is inclined to consider their findings to be reliable and informative. Yet, they resemble big fishing operations where all sorts of important and unimportant stuff is caught in the net. When studying such papers, it is wise to remember that associations do not necessarily reveal causal relationships!
Having said this, I find very little information in these already outdated results (they originate from 2014!) that I would not have expected. Perhaps the most interesting aspect is the nature of the most popular SCAMs used for musculoskeletal problems. The relatively high usage of MBBTs had to be expected; in most of the surveyed countries, massage therapy is considered to be not SCAM but mainstream. The fact that 6.5% used homeopathy to ease their musculoskeletal pain is, however, quite remarkable. I know of no good evidence to show that homeopathy is effective for such problems (in case some homeopathy fans disagree, please show me the evidence).
In my view, this indicates that, in 2014, much needed to be done in terms of informing the public about homeopathy. Many consumers mistook homeopathy for herbal medicine (which btw may well have some potential for musculoskeletal pain), and many consumers had been misguided into believing that homeopathy works. They had little inkling that homeopathy is pure placebo therapy. This means they mistreated their conditions, continued to suffer needlessly, and caused an unnecessary financial burden to themselves and/or to society.
Since 2014, much has happened (as discussed in uncounted posts on this blog), and I would therefore assume that the 6.5% figure has come down significantly … but, as you know:
I am an optimist.
I believe in progress.
Homeopathy is sometimes claimed to be effective for primary dysmenorrhoea (PD), but the claim is not supported by sound evidence. This study was undertaken to examine the efficacy of individualized homeopathic medicines (IH) against placebo in the treatment of PD.
A double-blind, randomized, placebo-controlled trial was conducted at the gynecology outpatient department of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India. Patients were randomized to receive either IH (n=64) or identical-looking placebo (n=64). Primary and secondary outcome measures were 0-10 numeric rating scales (NRS) measuring the intensity of pain of dysmenorrhea and verbal multidimensional scoring system (VMSS) respectively, all measured at baseline, and every month, up to 3 months.
The two groups were comparable at baseline. The attrition rate was 10.9% (IH: 7, placebo: 7). Differences between groups in both pain NRS and VMSS favored IH over placebo at all time points with medium to large effect sizes. Natrum muriaticum and Pulsatilla nigricans were the most frequently prescribed medicines. No harms, serious adverse events, or intercurrent illnesses were recorded in either group.
The authors concluded that homeopathic medicines acted significantly better than placebo in the treatment of PD. Independent replication is warranted.
A previously published RCT could not show any significant effect of homeopathy on primary dysmenorrhea in comparison with placebo. The authors of the new study claim that the discrepant findings might be due to the fact that IH requires great skill. In other words, negative studies are according to this explanation negative not because homeopathy does not work but because the prescribers are not up to it. Such notions have often been voiced on this blog and elsewhere and are used as a veritable ‘get-out clause’ for homeopathy: ONLY THE POSITIVE RESULTS ARE VALID! Consequently, systematic reviews of the evidence must only consider positive trials. And this, of course, means that the findings are invariable positive.
I find this more than a little naive and would much prefer to wait for an independent replication where ‘independent’ means that the trial is run by experts who are not advocates of homeopathy (as in the present trial).
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.
Bach flower remedies were invented in the 1920s by Dr. Edward Bach (1886-1936), a doctor homeopath who had previously worked in the London Homeopathic Hospital. They have since become very popular in Europe and beyond. Bach flower remedies are clearly inspired by homeopathy; however, they are not the same because they do not follow the ‘like cures like’ principle and are they potentized. They are manufactured by placing freshly picked specific flowers or parts of plants in water which is subsequently mixed with alcohol, bottled, and sold. Like most homeopathic remedies, they are highly dilute and thus do not contain therapeutic amounts of the plant printed on the bottle.
The aim of this new randomized, double-blind, placebo-controlled trial was to compare the efficacy of flower therapy for the treatment of anxiety in overweight or obese adults with that of a placebo. The authors examined improvement in sleep patterns, reduction in binge eating, and change in resting heart rate (RHR).
The study included 40 participants in the placebo group and 41 in the intervention group. Participants were of both genders, from 20 to 59 years of age, overweight or obese, with moderate to high anxiety. They were randomized into two groups:
- one group was treated with Bach flower remedies (BFR) (bottles containing 30 mL of 30% hydro-brandy solution with two drops each of Impatiens, White Chestnut, Cherry Plum, Chicory, Crab Apple, and Pine), purchased from Healing® Flower Essences (São Paulo, Brazil)
- the other group was given a placebo (same solution without BFR).
All patients were instructed to orally ingest the solutions by placing four drops directly in the mouth four times a day for 4 weeks.
The primary outcome was anxiety (State-Trait Anxiety Inventory [STAI]). Secondary outcomes were sleep (Pittsburgh Sleep Quality Index [PSQI]), binge eating (Binge Eating Scale [BES]), and RHR (electrocardiogram).
Multivariate analysis showed significant reductions in scores for the following variables in the intervention group when compared with the placebo group: STAI (β = −0.190; p < 0.001), PSQI (β = −0.160; p = 0.027), BES (β = −0.226; p = 0.001), and RHR (β = −0.07; p = 0.003).
The authors concluded that anxiety symptoms, binge eating, and RHRs of the individuals treated with flower therapy decreased, and their sleep patterns improved when compared with those treated with the placebo.
Did the alcohol in the verum preparation had a relaxing effect? No, I was teasing. The amount would have been too small and the effect would have been the same in both groups. But what could have caused the observed outcome? I have to admit that I have no idea.
I read the study several times and could not find a major flaw. Hence it must have been the flower remedy that caused the positive outcome? No, I am teasing again. I find this impossible to imagine. These remedies contain nothing that might explain the results and all previous systematic reviews of all the available trials have all reached a negative conclusion. Before I seriously consider the option that flower remedies are more than placebos, I would like to see an independent replication.
Ever since I published a post about the irresponsible and aggressive advertising campaign of LYMA (“the world’s 1st super-supplement”), I am pursued by them with emails informing me about the wonders of this supplement. Here is one I received recently:
Here at LYMA we are firm believers that optimal productivity depends on good quality sleep and your day is only as good as the previous night.
Suffering from bad sleep is debilitating whether it’s ourselves or we’re watching someone we love suffer, the search for good rest is something we’re all united in.
Energy levels, positive mindset and strong cognitive function all come from sleep, which is why we spent so long formulating the LYMA supplement. Our patented KSM-66® Ashwagandha is the highest-quality, zero toxicity, concentrated Ashwagandha root in the world. The hefty combination of purity and potency make it unrivalled in its ability to reduce inflammation, neutralise anxiety and promote deep, restful sleep, night after night.
Thousands of customers have told us that after years of bad sleep, they’re finally getting the rest they need and feeling transformed as a result. In fact, it’s one of the very first benefits most people notice. We’re happy to hear it.
And the knock-on effects of a good night’s sleep in how we feel, how we perform and our overall health are far reaching. Which is why we are so delighted to welcome Michael Grandner, world-renowned sleep expert and Director of the Behavioural Sleep Medicine Clinic, Arizona to the LYMA team.
Michael is one of the most cited sleep experts in the world and has himself published over 175 articles on issues relating to sleep and health. We plan on tapping into every area of his expertise to understand our own sleep habits and how we can all become the best at rest.
To introduce Michael to the LYMA community we’re hosting a seminar dedicated to understanding sleep on Tuesday 22nd June…
I was tempted to discard all this as rather pathetic advertising hype. But then I had second thoughts. This text does after all make several medical claims, and the question is: ARE THEY SUPPORTED BY EVIDENCE?
It claims that KSM-66® Ashwagandha:
- is the highest-quality, zero toxicity, concentrated Ashwagandha root in the world.
- That the hefty combination of purity and potency makes it unrivalled in its ability to reduce inflammation.
- That the product neutralises anxiety.
- That it promotes deep, restful sleep, night after night.
I ran a few searches to find out whether there is any sound evidence for any of these claims.
- There seem to be several supplements that contain,KSM-66® Ashwagandha’. The impression that LYMA is the only one is thus wrong. Zero toxicity must also be wrong; not even water has zero toxicity. In fact, epigastric pain/discomfort and loose stools were reported as most common (>5%); and giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain have all been associated with the herbal remedy. Moreover, if it is true that Ashwagandha stimulates the immune system, it might cause problems for people with autoimmune diseases.
- I found no compelling evidence from clinical trials to show that KSM-66® Ashwagandha reduces inflammatory conditions in humans.
- I found a study concluding that Ashwagandha given as an adjunct offered some potential advantages as a safe and effective adjunctive therapy to SSRIs in GAD. Yet, I found no compelling evidence from clinical trials to show that KSM-66® Ashwagandha as a single supplement reduces anxiety in otherwise healthy individuals.
- A 2021 study suggested that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Yet the authors cautioned that additional clinical trials are required to generalize the outcome.
So, what does that tell us?
It could mean that:
- My searches were not sufficiently thorough and that I have missed compelling evidence. If so, I would appreciate, if the LYMA promoters would show me their evidence so that I can assess it.
- The LYMA people are irresponsible and mislead the public with untenable claims.
I am looking forward to their response.
A PROVOCATION is an action or speech that makes someone annoyed or angry, especially deliberately. In law, provocation is when a person is considered to have committed an act partly because of a preceding set of events that might cause a reasonable person to lose self-control.
An INSULT is an expression, statement, or behavior which is disrespectful or scornful. Insults may be intentional or accidental. An insult may be factual, but at the same time pejorative.
An AD HOMINEM ATTACK is an attack on the character of a person who tends to feel the necessity to defend himself or herself from the accusation.
Despite all my attempts to keep the exchanges on this blog reasonably polite, civil, and respectful, I seem to have been less than successful. This, of course, is not least my fault. I am as prone to lose my temper as anyone else, and I admit that, after decades of discussing with irrational people, my patience wears thin.
What should we do about it?
To start with, we need to understand what typically happens. In most cases, things start with a provocation. Let’s consider a recent example. As a response to my perfectly non-provocative post entitled A LOOK AT MY OWN PUBLICATIONS, I got this response:
“Surprisingly, not many of these papers are in the ‘top 100’. I am not sure whether this is meaningful and if so how I should interpret this.”
Perhaps your fame was overshadowed after Hahn showed that you manipulate data and now you are taken seriously into account only by foreign lobbies (such as the “Questao da Ciencia Institute”) and German lobby that you run from your country. It’s normal, Ernst, it’s not surprising that your colleague Natalia Pasternak pathetically cites your book in her article to justify the elimination of homeopathy in Brazil.
As we had discussed Robert Hahn’s misunderstanding of my research several times previously on this blog, my response was to simply post one of the posts that had dealt with the issue. The comment that followed was even more insulting than his previous one. My reaction was to ban the author.
This course of events is fairly typical. Normally, the sequence is as follows:
- I (or someone else) post something that displeases a reader.
- He responds with a provocation.
- I give him back accordingly.
- Things escalate until he posts one or more full-blown insults or ad hominem attacks.
- Eventually, I ban the author.
I wonder how these unpleasantries might be avoided.
- I could phrase my posts in a way that is less provocative to fans of so-called alternative medicine (SCAM). I have often considered doing this. So far, I have mostly decided against it, because I feel a certain amount of provocation is healthy and needed to stimulate discussions. If I changed my style, it would be at the cost of the interest this blog often attracts.
- I could refuse to give back in the same coinage as I receive. This is precisely what I very often try. Yet, sometimes I fail. Sorry!
- I could be much stricter and ban people at the first signs of misbehavior. This, I fear, would take much of the spice and excitement out of our discussions and reduce the entertainment value of my blog.
There is no easy solution, as far as I can see.
For the time being, I will try harder to be polite and civil, and I do beg all of my readers to do the same. Other than this, there is not much that I will change. Oh, I almost forgot: there is also this previous post of mine which I usually send to people who, in my view, have overstepped the mark. It might serve as a caution that I am considering banning that person if things don’t improve.
Bottom line: thanks everyone for your efforts to control your aggressions!
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?
- Most primary studies were of very poor quality.
- Most were from China, and we know (and have often discussed) that such trials are most unreliable.
- 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