medical ethics
In the UK, a new post-Brexit regulatory framework is being proposed for food supplements by the government. The nutraceutical sector is estimated to be worth £275bn globally and £4bn in the UK. A new report claims that “science is starting to point the way to a new sector of nutritional products with increasingly explicable and/or verifiable medicinal benefits, which needs to be reflected in our regulatory framework.” Tory MP George Freeman, one of the authors of the report, was quoted saying:
“We are living through an extraordinary period of technological change – not just in life science but in host of sectors: from AI to robotics to agri-tech, nutraceuticals, nanotechnology, synthetic biology, biofuels, satellites and fusion energy. The UK is indeed a ‘science superpower’. But we have traditionally been woeful at commercialising here in the UK. There are many reasons. But, in recent years, the EU’s increasingly slow, bureaucratic and ‘precautionary’ approach – copied in Whitehall – has made the EU and the UK an increasingly poor place to commercialise new technology.”
If a product like a food or a herbal remedy makes ‘medicinal’ claims, it is currently regulated by the MHRA. If a product only makes general ‘health’ claims, it is regulated by the Department of Health and Social Care in England, by the FSA in Wales and Northern Ireland, and by Food Standards Scotland in Scotland. This ‘patchwork of regulators’ is bound to change as it is deemed to create additional costs and uncertainty for businesses who would like to see the relevant functions brought together in a central regulatory body and a clearer UK landscape.
In response to the task force’s report, PM Boris Johnson stated that bold and ambitious ideas such as these are needed to encourage growth and innovation:
“The Government, through our Better Regulation Committee, is already hard at work on reform of the UK’s regulatory framework. Your bold proposals provide a valuable template for this, illustrating the sheer level of ambitious thinking needed to usher in a new golden age of growth and innovation right across the UK. So we will give your report the detailed consideration it deserves, consult widely across industry and civil society, and publish a response as soon as is practicable.”
Am I the only one who feels more than a little uneasy about all this? I honestly do not see much new science that, according to the report, points to ‘verifiable medicinal benefits’ of food supplements or nutraceuticals. What the report does however point to, I fear, is that the UK government is about to deregulate quackery with a view to making some entrepreneurs wealthy snake oil salesmen at the cost of public health and wealth.
I hope I am mistaken.
RNZ reported that New Zealand doctors spreading misinformation about Covid-19 may lose their job. Medical Council chair Dr Curtis Walker said a small number of doctors were peddling conspiracies. “It’s questioning the severity of Covid, it’s questioning the safety of vaccination, it’s questioning whether the whole thing is a conspiracy theory. You know you name it, this is what’s been put out there.”
The council has received 13 complaints about medical staff from the public this year – although that included instances of multiple complaints about the same doctor. It comes after it was reported last month that dozens of heath professions, including GPs, signed an open letter opposing the Pfizer vaccine.
Dr Walker said an independent body was investigating to decide if charges should be laid with the Health Practitioners Disciplinary Tribunal. Doctors have a professional duty to provide advice based on evidence, he said. “There’s a mountain of evidence out there of how effective and safe the Covid vaccine is. And we’ve already seen the alternative of unvaccinated populations where millions have died.” Walker said doctors were particularly respected members of the community and their opinions about health carried extra weight. Any found spreading misinformation could potentially lose their jobs and the right to practice medicine.
NZ Royal College of General Practitioners president Dr Samantha Murton said while people could choose not to get vaccinated there were serious consequences if the virus breached the borders. “If those vulnerable people are being given misinformation, they may choose to do something that’s really detrimental to their health. What worries me the most is the poorer people, the people who are at higher risk. If they’re getting this … misinformation then it’s potentially putting their lives in jeopardy.”
Kate Hannah, who researches misinformation at the University of Auckland, said anyone could be sucked in – including highly educated people such as doctors. Most misinformation originated overseas – with people here adapting it to target particular demographics, she said. “And in doing so it targets people’s lived experiences of things like racism in the health system or racism more broadly, or say women’s experiences of the health system where they may have experiences of previously not being listened to.”
Ways to spot misinformation included if someone was trying to sell you something; was asking for donations; or the information was presented to elicit an emotional reaction. “If it’s written in a way that makes you feel upset or scared, or nervous or fearful, you know that’s not normally how we convey good quality public health information. Good quality public health information should provide you with information and make you feel reassured and calm and like you can make good decisions.” Other red flags included asking for personal information or to sign up to receive regular updates – ways to separate you from your current community or sources of information, Hannah said. Covid conspiracies could act as as a gateway, exposing people to online communities espousing far right ideology, misogyny, racism and transphobia, she said.
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Willful misinformation about a serious health matter amounts to a violation of medical ethics. It, therefore, stands to reason that healthcare professionals who engage in such activities should be reprimanded. If that is so, it applies not just to COVID-19 but to any medical misinformation. Moreover, I should not just apply to doctors, but to all healthcare professionals.
If we do this systematically, it would mean that also providers of so-called alternative medicine (SCAM) might get struck off their professional register, if they make unsubstantiated claims in cases of serious illnesses.
Not realistic, you say?
Why not? After all, medical ethics cannot be bent to protect the interests of SCAM professionals.
WHAT DO YOU THINK?
I have repeatedly reported about what has been happening with homeopathy in France. For many decades, it had a free ride. Things began to change some 10 years ago.
- In 2014, our book was published in French. I might be fooling myself, but I do hope that it helped to start a ball rolling.
- Subsequently, French skeptics began raising their voices against quackery in general and homeopathy in particular.
- In 2015, Christian Boiron, boss of Boiron, stated about people opposing homeopathy that “Il y a un Ku Klux Klan contre l’homéopathie” THERE IS A KU KLUX KLAN AGAINST HOMEOPATHY”.
- In 2018, 124 doctors published an open letter criticizing the use of so-called alternative medicine (SCAM).
- In the same year, the Collège National des Généralistes Engseignants, the national association for teaching doctors, pointed out that there was no rational justification for the reimbursement of homeopathics nor for the teaching of homeopathy in medical schools, and they stated bluntly that it is necessary to abandon these esoteric methods, which belong in the history books.
- Also in 2018, the University of Lille announced its decision to stop its course on homeopathy. The faculty of medicine’s dean, Didier Gosset, said: It has to be said that we teach medicine based on proof – we insist on absolute scientific rigor – and it has to be said that homeopathy has not evolved in the same direction, that it is a doctrine that has remained on the margins of the scientific movement, that studies on homeopathy are rare, that they are not very substantial. Continuing to teach it would be to endorse it.
- In 2019, the French Academies of Medicine and Pharmacy published a document entitled ‘L’homéopathie en France : position de l’Académie nationale de médecine et de l’Académie nationale de pharmacie’. It stated that L’homéopathie a été introduite à la fin du XVIIIe siècle, par Samuel Hahnemann, postulant deux hypothèses : celle des similitudes (soigner le mal par le mal) et celle des hautes dilutions. L’état des données scientifiques ne permet de vérifier à ce jour aucune de ces hypothèses. Les méta-analyses rigoureuses n’ont pas permis de démontrer une efficacité des préparations homéopathiques. The academies concluded that no French university should offer degrees in homeopathy, and that homeopathy should no longer be funded by the public purse: “no homeopathic preparation should be reimbursed by Assurance Maladie [France’s health insurance] until the demonstration of sufficient medical benefit has been provided. No university degree in homeopathy should be issued by medical or pharmaceutical faculties … The reimbursing of these products by the social security seems aberrant at a time when, for economic reasons, we are not reimbursing many classic medicines because they are more or less considered to not work well enough …”
- Only weeks later, the French health regulator (HAS) recommended with a large majority the discontinuation of the reimbursement of homeopathic products.
- The health minister, Agnès Buzyn, announced “Je me tiendrai à l’avis de la Haute Autorité de santé”.
- Consequently, the powerful French homeopathy lobby mounted political pressure, including a petition with over 1000000 signatures.
- President Macron allegedly was hesitant and considered a range of options, including a reduction of the percentage of reimbursement.
- Apparently, the minister stood up for science and, as rumored, even put her job on the line.
- In July 2019, she announced the end of reimbursement and was quoted saying “J’ai toujours dit que je suivrais l’avis de la Haute Autorité de santé (HAS), j’ai donc décidé d’engager la procédure de déremboursement total“
Since then, homeopathy has indeed been banned from reimbursement. Here is a short update on the current situation: 
After the disengagement of the French Social Security system, the world leader in homeopathy has been trying to convince complementary health insurance companies to take up the torch of large-scale reimbursement. Its seduction operation includes a third-party payment solution to boost sales.
From 1 January 2021, homeopathy is no longer reimbursed by Social Security. In March 2020, Boiron, the largest producer of homeopathics, began a restructuring that led to the loss of 560 jobs in France and the closure of one-third of its 31 production and distribution sites. On Thursday, the site of Chauray (Deux-Sèvres) closed after 33 years of activity.
… The CEO of Boiron, Valérie Lorentz-Poinsot, does not have words strong enough to describe the decision of the former Minister of Health, Agnès Buzyn, to delist homeopathy. Since the view issued in June 2019 by the French Health Authority (HAS) noting the ineffectiveness of 1,100 of these products previously reimbursed by the French health service, the reimbursement of homeopathics was reduced from 30% to 15% in 2020, then to 0% on 1 January 2021.
PS
Oh, I almost forgot to mention: the stocks in Boiron roughly halved during the last 3 years
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.
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.
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.
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.13548As I have reported previously, homeopathy has recently had a hard time in Germany. The following short note appeared in the German Medical Journal. Allow me to translate it for you:
The Higher Administrative Court of Bremen has rejected as inadmissible the application for a judicial review by a Bremen physician against the deletion of the ‘HOMEOPATHY’-title from the further training regulations of the Bremen Medical Association (decision of June 2, 2021). Thus, the new regulation for postgraduate training of the Bremen Medical Association without the additional designation of homeopathy has been upheld.
“We are very pleased that the Court shares our legal opinion and has rejected the plaintiff’s application,” said Heike Delbanco, Chief Executive Officer of the Bremen Medical Association. “This is also a clear signal for other German medical associations where comparable lawsuits against the removal of homeopathy from the canon of additional designations are pending.”
The Assembly of Delegates of the Medical Association had decided in September 2019 on a new training regulation, which – unlike the previous regulation – no longer provided for the postgraduate training in homeopathy. After the expiry of a transitional period, the qualification of homeopathy can therefore no longer be acquired at the Bremen Medical Association; however, titles already acquired can continue to be held.
A physician from Bremen, who holds the title of homeopathy, brought an action before the Higher Administrative Court against the cancellation of the additional title. He claimed that the removal of the additional designation from the continuing education regulations interfered with his fundamental right to freedom of profession and his fundamental right to property and complained of a violation of the general principle of equality. The medical association considered the action inadmissible.
The Higher Administrative Court now rejected the application, since a violation of the plaintiff’s rights could not be recognized. The plaintiff can continue to use his title HOMEOPATHY also under the new regulations.
The expectations presented by him – in particular, the expectation to find suitable practice representatives and to be able to sell his practice on retirement at a profit – do not justify any legal positions protected by fundamental rights and consequently also no obligation of the Bremen Medical Association to enable physicians to obtain the additional title of homeopathy in future.
________________________
As several further medical associations in Germany have banned homeopathy in the same way as Bremen and were consequently also taken to court by homeopathy enthusiasts, one can be optimistic that these cases will also go against homeopathy.
You may have noticed that my patience with homeopathy, homeopaths, and other providers of so-called alternative medicine (SCAM) has diminished. In fact, I do not think much of quacks of all shades and no longer muster much understanding. It is better, so I mean after approximately 30 years of discussions with snake oil salesmen and other charlatans, to offer such people Parole. Facts are facts, and no one should be allowed to ignore that without contradiction.
That was not always the case.
When I began as Chair of Complementary Medicine at Exeter in 1993, I was optimistic. It was clear to me that my task of scrutinizing this field would not be easy and could occasionally bring me into conflict with enthusiasts. But I was determined to build bridges, to remain polite, and to muster as much understanding as necessary.
And so I began to build a multidisciplinary team, conduct research, and publish it. My goal was to do as rigorous science as possible and, if avoidable, not to step on anyone’s toes in the process. Especially with regard to homeopathy, my general attitude was quite positive. Accordingly, my articles were as favorable as the evidence allowed. My goal was to emphasize the good aspects of homeopathy wherever possible.
What, you find that hard to believe?
Then you are in good company!
Homeopaths like to claim that I was out to malign not only homeopathy but all of SCAM from the beginning. That this assumption is not true, I tried to demonstrate in an article entitled ‘Homeopathy and I’. In this paper, I merely extracted typical passages from my publications. From them, you can probably see how my attitude slowly changed over the years. See for yourself (sorry for the length of the list):
- 1. homeopathic remedies are believed by doctors and patients to be almost totally safe (Ernst E, White A. Br J Gen Pract 1995; 45: 629-30)
- 2. it might be argued that arnica … is ineffective but homeopathy may still work (Ernst E. BMJ 1995; 311: 510-1)
- 3. homeopathy, I fear, has soon to come up with … more convincing evidence (Ernst E. Forsch Komplementarmed 1995; 2: 32)
- 4. future evaluations of homeopathy should be performed to a high scientific standard (Ernst E. Br Homeopath J 1995; 84: 229)
- 5. the best way forward is clearly to do rigorous research (Ernst E, Kaptchuk TJ. Arch Intern Med 1996; 156: 2162-4)
- 6. the most pressing question, ‘Is homeopathy clinically more effective than placebo’, needs to be answered conclusively (Ernst E. Br J Clin Pharmacol 1997; 44: 435-7)
- 7. there is evidence that homeopathic treatment can reduce the duration of ileus (Barnes J, Resch KL, Ernst E. J Clin Gastroenterol 1997; 25: 628-33)
- 8. the published evidence to date does not support the hypothesis that homeopathic remedies … are more efficacious than placebo (Ernst E, Barnes J. Perfusion 1998; 11: 4-8)
- 9. the claim that homeopathic arnica is efficacious beyond a placebo effect is not supported by rigorous clinical trials (Ernst E, Pittler MH. Arch Surg 1998; 133: 1187-90)
- 10. … the trial data … do not suggest that homeopathy is effective (Ernst E. J Pain Sympt Manage 1999; 18: 353-7)
- 11. … the re-analysis of Linde et al. can be seen as the ultimate epidemiological proof that homeopathic remedies are, in fact, placebos (Ernst E, Pittler MH.J Clin Epidemiol 2000; 53: 1188)
- 12. … homeopathy is not different from placebo (Ernst E, Pittler MH. J Clin Epidemiol 2002; 55: 103-4)
- 13. … the best clinical evidence … does not warrant positive recommendations (Ernst E. Br J Clin Pharmacol 2002; 54: 577-82)
- 14. the results of this trial do not suggest that homeopathic arnica has an advantage over placebo (Stevinson C, Devaraj VS, Fountain-Barber A, Hawkins S, Ernst E. J R Soc Med 2003; 96: 60-5)
- 15. this study provides no evidence that adjunctive homeopathic remedies … are superior to placebo (White A, Slade P, Hunt C, Hart A, Ernst E. Thorax 2003; 58: 317-21)
- 16. … this systematic review does not provide clear evidence that the phenomenon of homeopathic aggravations exists (Grabia S, Ernst E. Homeopathy 2003; 92: 92-8)
- 17. … the proven benefits of highly dilute homeopathic remedies … do not outweigh the potential for harm (Ernst E.Trends Pharmacol Sci 2005; 26: 547-8)
- 18 Our analysis … found insufficient evidence to support clinical efficacy of homeopathic therapy (Milazzo S, Russell N, Ernst E. Eur J Cancer 2006; 42: 282-9)
- 19. … promotion can be regrettably misleading, or their effectiveness? (Ernst E. J Soc Integr Oncol 2006; 4: 113-5)
- 20. … homeopathy is not based on solid evidence and, over time, this evidence seems to get more negative (Ernst E, Pittler MH, Wider B, Boddy K. Perfusion 2006; 19: 380-2)
- 21. the evidence from rigorous clinical trials … testing homeopathy for childhood and adolescence ailments is not convincing enough for recommendations in any condition (Altunc U, Pittler MH, Ernst E. Mayo Clin Proc 2007; 82: 69-75)
- 22. … context effects of homeopathy … are entirely sufficient to explain the benefit many patients experience (Ernst E. Curr Oncol 2007; 14: 128-30)
- 23. among all the placebos that exist, homeopathy has the potential to be an exceptionally powerful one (Ernst E. Br J Clin Pharmacol 2008; 65: 163-4)
- 24. … recommendations by professional homeopathic associations are not based on the evidence (Ernst E. Br J Gen Pract 2009; 59: 142-3)
These quotes speak for themselves, I think. But what was the reason for the change? As far as I can judge in retrospect, there were three main reasons.
1. The data became clearer and clearer
When I started researching homeopathy, at least the clinical evidence was not clearly negative. In 1991, Jos Kleinjen had published his much-noted systematic review in the BMJ. Here is its conclusion:
At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials.
Subsequently, more and better clinical trials were published, and the overall picture became increasingly negative. Kleinjen, who had become somewhat of a hero in the realm of homeopathy, re-reviewed the evidence in 2000 and concluded that there are currently insufficient data to either recommend homoeopathy as a treatment for any specific condition or to warrant significant changes in the provision of homoeopathy.
The 24 citations above reflect this development quite nicely. Today, there is no longer much doubt that highly-diluted homeopathic remedies are pure placebos. This is perhaps most clearly expressed in the now numerous statements of high-ranking international bodies.
2. The lack of understanding on the part of homeopaths
So the evidence is now clear. But it may not fully explain why my patience with homeopaths diminished. To understand this better, one must consider the utter lack of insight of today’s homeopaths (think, for example, of the incredible Ebola story).
It is of course understandable that a homeopath would be less than enthusiastic about the increasingly negative evidence. But homeopaths are also physicians or at least medically untrained practitioners (lay homeopaths). As such, they have an obligation to acknowledge the overwhelming evidence and act accordingly. That they quite obviously do not do so, is not only regrettable but also highly unethical and shameful. In any case, I find it difficult to have much patience for such people.
3. Personal attacks
In the many years that I have now been scrutinizing SCAM, I have become used to being attacked. The attacks and insults I have received, especially from homeopaths, are legion. For example, when we published our arnica study, we were threatened with letter bombs. However, one should keep one thing in mind: ad hominem attacks are a victory of reason over unreason. If one is personally attacked by one’s opponent, it only shows that he has run out of rational arguments.
Perhaps the most impressive example of an attack was not directed against me personally, but across the board against all who dare to doubt homeopathy. Christian Boiron is the boss of the world’s largest homeopathic manufacturer, Boiron. In an interview he was once asked what he thought of homeopathy critics; his answer: “Il y a un Ku Klux Klan contre l’homéopathie” (There is a Ku Klux Klan against homeopathy).
Yes, many of these attacks even have something comical about them; nevertheless, they are not likely to increase my patience with homeopaths. This does not mean, however, that I will soon hang my opponents from the nearest tree in the old KKK tradition. I’ll gladly leave such tasteless ideas to Christian Boiron.
A few months ago, I started contributing to a German blog. This has been fun but only moderately successful in terms of readership. This week, I posted something about a homeopath and his strange attitude towards COVID vaccinations. This post was so far read by around 20 000 people!
As it was so unusually successful (and because there is a big conference today on the subject), I decided to translate it for my non-German readers.
Here we go:
A lot of downright silly stuff is currently being written about vaccine side effects at the moment, not least on Twitter where I recently found the following comment from a medical colleague:
I’ve been a doctor for 25 years now. I have never experienced such an amount of vaccine side effects. I can’t imagine that other colleagues feel differently.
This kind of remark naturally makes you think. So let’s think a little bit about these two sentences. In particular, I would like to ask and briefly answer the following questions:
- How reliable is this physician’s impression?
- What does the reliable evidence say?
- Is it conceivable that this doctor is mistaken?
- What might be the causes of his error?
- Who is the author?
- Why is the tweet questionable?
1. How reliable is this doctor’s impression?
A whole 25 years of professional experience! So we are dealing with a thoroughly experienced doctor. His statement about the current unusually large amount of vaccination side effects should therefore be correct. Nevertheless, one should perhaps bear in mind that the incidence of side effects cannot be determined by rough estimations, but must be precisely quantified. In addition, we also need data on the severity and duration of symptoms. For example, is it only mild pain at the injection site or venous thrombosis? Are the symptoms only temporary, long-lasting, or even permanent? In general, it must be said that the experience of a physician, while not completely insignificant, does not constitute evidence. Oscar Wilde once said, “experience is the name we give to our mistakes.”
2. What does the reliable evidence tell us?
Even if the good doctor had 100 years of professional experience and even if he could accurately characterize the side effects, his experience would be trivial compared to the hard data we have on this subject. Nearly 2 billion vaccinations have now been performed worldwide, and we are therefore in the fortunate position of having reliable statistics to guide us. And they show that side effects such as pain at the injection site, fatigue, and headaches are quite common, while serious problems are very rare.[1] A recent summary comes to the following conclusion (my translation)[2]:
The current data suggests that the currently approved mRNA-based COVID-19 vaccines are safe and effective for the vast majority of the population. Furthermore, broad-based vaccine uptake is critical for achieving herd immunity; an essential factor in decreasing future surges of COVID-19 infections. Ensuring sufficient COVID-19 vaccination adoption by the public will involve attending to the rising vaccine hesitancy among a pandemic-weary population. Evidence-based approaches at the federal, state, city, and organizational levels are necessary to improve vaccination efforts and to decrease hesitancy. Educating the general public about the safety of the current and forthcoming vaccines is of vital consequence to public health and ongoing and future large-scale vaccination initiatives.
3. Is it conceivable that this doctor is mistaken?
In answering this question, I agree with Oscar Wilde. The evidence very clearly contradicts the physician’s impression. So the doctor seems to be mistaken — at least about the incidence of side effects that are not completely normal and thus to be expected. Even if indeed ‘other colleagues feel no differently’, such a cumulative experience would still mislead us. The plural of ‘anecdote’ is ‘anecdotes’ and not ‘evidence’.
4. What might be the causes of his error?
I wonder whether our doctor perhaps did not see or did not want to see the following circumstance: It is inevitable that a physician, at a time when soon 50% of all Germans were vaccinated, also sees a lot of patients complaining about side effects. He has never seen anything like that in his 25-year career! That’s because we haven’t been hit by a pandemic in the last 25 years. For a similar reason, the colleague will treat far fewer frostbites in midsummer than during a severe winter. The only surprising thing would be not to see more patients reporting vaccine side effects during the biggest vaccination campaign ever.
5. Who is the author?
At this point, we should ask, who is actually the author and author of the above tweet? Perhaps the answer to this question will provide insight into his motivation for spreading nonsense? Dr. Thomas Quak (no, I did not invent the name) is a practicing homeopath in Fürstenfeldbruck, Germany. Like many homeopaths, this Quak probably has a somewhat disturbed relationship to vaccination. In his case, this goes as far as recommending several vaccine-critical machinations on his website and even offering ‘critical vaccination advice’ as a special service.[3]
Now we can immediately put the Quak tweet in a better perspective. Dr. Quak is a vaccination opponent or critic and wants to warn the public: for heaven’s sake, don’t get vaccinated folks; side effects are more common than ever!!!! Therefore, he also conceals the fact that the side-effects are completely normal, short-term vaccination reactions, which are ultimately of no significance.
6. Why is the tweet concerning?
Perhaps you feel that the Quak and his Quack tweet are irrelevant? What harm can a single tweet do, and who cares about a homeopath from Fürstenfeldbruck? As good as none and nobody! However, the importance does not lie in a single homeopath unsettling the population; it consists in the fact that such things currently happen every day thousandfold.
In their narrow-mindedness, vaccination opponents of all shades want to make us believe that they are concerned about our well-being because they know more than we and all the experts (who are of course bought by the pharmaceutical industry). But if you scratch just a little at the surface of their superficiality, it turns out that the exact opposite is true. They are ill-informed and only interested in spreading their hare-brained, misanthropic ideology.
And why do homeopaths do this? There are certainly several reasons. Although Hahnemann himself was impressed by the success of vaccination, which was invented in his time and hailed as a breakthrough, most of his successors soon sided with vaccination critics. Many do so by warning (like our Quak) of side effects, thinking that they are thus protecting their patients. However, they ignore two very important points:
- Even if the dangers of vaccinations were much greater than they actually are (no one is claiming that they are completely harmless), the benefits would still far outweigh the potential harms.
- If the Quaks (and all the quacks) of this world succeeded in dissuading a sizable percentage of the population from vaccinating and thus save them from the ‘oh-so-dangerous side effects’, they would still be doing a real disservice to public health. With regard to COVID-19, this would mean that the pandemic would remain with us in the long term and cost many more lives.
Whatever the motives of the homeopathic anti-vax brigade, it is certain that their attitude is a threat to our health. This has repeatedly made me state:
The homeopathic pills may be harmless, but unfortunately, the homeopaths are not!
REFERENCES
- COVID-19 vaccine availability: what are the side effects? | British Journal of General Practice (bjgp.org) ︎
- Review the safety of Covid-19 mRNA vaccines: a review – PubMed (nih.gov) ︎
- Vaccination Information (doktor-quak.de) ︎
