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

scientific misconduct

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It has been reported that the US Insurer ‘State Farm’ is fighting a fraudulent scheme that has been exploiting New Jersey’s personal injury protection (PIP) benefits law since 2014. The insurer is seeking to recover $2.6 million in what it claims are fraudulent auto injury claims and a declaratory judgment that it need not pay any further claims submitted by the providers involved in the alleged scheme.

State Farm’s suit accuses 12 chiropractic and spine clinics and doctors of fraud, unjust enrichment, and violations of the New Jersey Insurance Fraud Prevention Act. The insurer alleges these providers used a “predetermined protocol” for all patients and a patient referral system for services that were either not performed or were not medically necessary for the individual patients. Instead, the services were carried out to enrich the defendants by exploiting the patients’ eligibility for PIP benefits, according to the complaint.

The suit accuses the providers of failing to legitimately evaluate patients to determine the true nature of their injuries and of reporting the same or similar findings for all patients to justify a predetermined course of treatment that was substantially the same for all patients. Part of the “predetermined protocol” for patients with soft-tissue injuries of the neck and back consisted of

  • hot and cold packs,
  • chiropractic manipulations,
  • massage,
  • mechanical traction,
  • physical medicine and rehabilitation,
  • and manual therapy.

These treatments were administered to almost every patient on almost every visit, regardless of each patient’s unique circumstances and needs, according to the complaint. The chiropractors are also accused of referring patients to diagnostic clinics, some allegedly illegally owned by the chiropractors, for an “unnecessary and predetermined course of pain management and invasive treatments” including injections. State Farm says they would submit false documentation for each case representing that the treatments were legitimately performed and medically necessary.

The 80-page complaint details case after case where the patient’s responses to questions and tests were the same or similar, allegedly serving as a “pretext to justify” the chiropractors’ wide range of treatments. The defendants in the complaint filed in U.S. District Court for New Jersey are:

  • Tri-County Chiropractic and Rehabilitation Center,
  • Robert Matturro, D.C.,
  • Advanced Spine and Pain Management,
  • Varinder Dhillon, M.D.,
  • Nicholas Rosania, D.C.,
  • Bloomfield UAI,
  • Dov Rand, M.D.,
  • Primary Medical Services,
  • Louis J. Citarelli, M.D.,
  • Chiro Health Center P.C.,
  • Marc Matturro, D.C.
  • Marco Tartaglia, M.D.

_____________________________

This story made me wonder: which of the listed treatments

  • hot and cold packs,
  • chiropractic manipulations,
  • massage,
  • mechanical traction,
  • physical medicine and rehabilitation,
  • and manual therapy

would ever be indicated for patients with soft-tissue injuries of the neck and back? Or more specifically, are chiropractic manipulations indicated or contra-indicated for such problems following a car accident? I fail to see any sound evidence that they are effective. If I am correct, should insurance companies not sue all chiropractors who routinely use manipulations for such cases? If the answer is YES, the sum of 2.6 million might need to be increased by several orders of magnitude.

According to the authors of this study, research is lacking regarding osteopathic approaches in treating polycystic ovary syndrome (PCOS), one of the prevailing endocrine abnormalities in reproductive-aged women. Limited movement of pelvic organs can result in functional and structural deficits, which can be resolved by applying visceral manipulation (VM). Already with these two introductory sentences, I have problems. But for the moment, we can leave this aside and have a look at their trial.

The study was aimed at analyzing the effect of VM on dysmenorrhea, irregular, delayed, and/or absent menses, and premenstrual symptoms in PCOS patients.

Thirty Egyptian women with PCOS, with menstruation-related complaints and free from systematic diseases and/or adrenal gland abnormalities, prospectively participated in a single-blinded, randomized controlled trial. They were recruited from the women’s health outpatient clinic in the faculty of physical therapy at Cairo University, with an age of 20-34 years, and a body mass index (BMI) ≥25, <30 kg/m2. Patients were randomly allocated into two equal groups (15 patients); the control group received a low-calorie diet for 3 months, and the study group received the same hypocaloric diet plus VM to the pelvic organs and their related structures, according to assessment findings, for eight sessions over 3 months. Evaluations for body weight, BMI, and menstrual problems were done by weight-height scale, and menstruation-domain of Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ), respectively, at baseline and after 3 months of treatments.

A total of 30 patients were included, with baseline mean age, weight, BMI, and menstruation domain score of 27.5 ± 2.2 years, 77.7 ± 4.3 kg, 28.6 ± 0.7 kg/m2, and 3.4 ± 1.0, respectively, for the control group, and 26.2 ± 4.7 years, 74.6 ± 3.5 kg, 28.2 ± 1.1 kg/m2, and 2.9 ± 1.0, respectively, for the study group. Of the 15 patients in the study group, uterine adhesions were found in 14 patients (93.3%), followed by restricted uterine mobility in 13 patients (86.7%), restricted ovarian/broad ligament mobility (9, 60%), and restricted motility (6, 40%). At baseline, there was no significant difference (p>0.05) in any of the demographics (age, height), or dependent variables (weight, BMI, menstruation domain score) among both groups. Post-study, there was a statistically significant reduction (p=0.000) in weight, and BMI mean values for the diet group (71.2 ± 4.2 kg, and 26.4 ± 0.8 kg/m2, respectively) and the diet + VM group (69.2 ± 3.7 kg; 26.1 ± 0.9 kg/m2, respectively). For the improvement in the menstrual complaints, a significant increase (p<0.05) in the menstruation domain mean score was shown in the diet group (3.9 ± 1.0), and the diet + VM group (4.6 ± 0.5). On comparing both groups post-study, there was a statistically significant improvement (p=0.024) in the severity of menstruation-related problems in favor of the diet + VM group.

The authors concluded that VM yielded greater improvement in menstrual pain, irregularities, and premenstrual symptoms in PCOS patients when added to caloric restriction than utilizing the low-calorie diet alone in treating that condition.

VM involves the manual manipulation by a therapist of internal organs, blood vessels and nerves (the viscera) mostly from outside the body, but sometimes, the therapist also puts his/her fingers into the patient’s vagina. It was developed by the osteopath Jean-Piere Barral. He stated that through his clinical work with thousands of patients, he created this modality based on organ-specific fascial mobilization. And through work in a dissection lab, he was able to experiment with visceral manipulation techniques and see the internal effects of the manipulations. According to its proponents, visceral manipulation is based on the specific placement of soft manual forces looking to encourage the normal mobility, tone, and motion of the viscera and their connective tissues. The idea is that these gentle manipulations may potentially improve the functioning of individual organs, the systems the organs function within, and the structural integrity of the entire body.

I don’t see any reason to believe the concepts of VM are plausible. Thus I find the hypothesis of this trial extremely far-fetched. The results are equally unconvincing. As we have often discussed, the ‘A+B vs B’ design cannot prove a causal relationship between the intervention and the outcome.

The most likely explanation for the findings is that the patients receiving VM experienced or merely reported improvements because the extra attention of mildly invasive treatments produced a powerful placebo effect. To put it bluntly: this is a poor, arguably unethical study where over-enthusiastic researchers reach a conclusion that is not supported by the data.

Trevor Zierke is a D.C. who published several videos that have gone viral after saying that “literally 99% of my profession” is a scam. “When I say almost all the usual lines chiropractors tell you are lies, I mean almost all of them,” he stated. Zierke then went on to give examples of issues chiropractors allegedly make up, including someone’s spine being “misaligned,” tension on nerves causing health problems, and someone having back pain because their hips are off-center. “Almost all of these aren’t true,” he concluded.

In a follow-up video, he claimed that the reasons most people are told they need to go to a chiropractor are “overblown or just flat out lies proven wrong by research.” He also noted that, while there are many scams, that “doesn’t mean you can’t get help from a chiropractor.”

In a third TikTok video, Zierke offered some valid reasons to see a chiropractor. He said that one can seek help from a chiropractor if one has musculoskeletal pain that has been ongoing for more than one to two days, and that’s about it. He stated that issues that a chiropractor couldn’t really fix include “GI pain, hormonal issues, nutrition,” among others.

In comments, users were largely supportive of Zierke’s message.

One said: “As a physiotherapist, I’ve been trying to tell this but I don’t want to like offend any chiropractor in doing so,” a commenter shared.

“Working in a chiropractic office, this is fair,” a further user wrote. “I have issues that I know an adjustment will help & other pain that would be better stretched/released.”

In an email, Zierke reiterated the intention of his videos: “I would just like to clarify that chiropractors, in general, are not a scam or are inherently scammers (I myself am a practicing chiropractor), but rather a lot of very popular sales tactics, phrases, and wording used to imply patients need treatment, and methods of treatment, have never been proven to be true,” he explained. “When chiropractors say & use these methods stating things that are not factually true—I believe it’s scammy behavior and practices. There are still a lot of very good, honest, and integral chiropractors out there,” he concluded. “They can provide a lot of help and relief to patients. But that’s unfortunately not the majority, and I’ve heard too many stories of people falling victim to some of these scam-like tactics from bad apple chiropractors.”

None of what DC Zierke said can surprise those who have been following my blog. On the contrary, I could add a few recent posts to his criticism of chiropractic, for example:

I rest my case.

Should Acupuncture-Related Therapies be Considered in Prediabetes Control?

No!

If you are pre-diabetic, consult a doctor and follow his/her advice. Do NOT do what acupuncturists or other self-appointed experts tell you. Do NOT become a victim of quackery.

But the authors of a new paper disagree with my view.

So, let’s have a look at the evidence.

Their systematic review was aimed at evaluating the effects and safety of acupuncture-related therapy (AT) interventions on glycemic control for prediabetes. The Chinese researchers searched 14 databases and 5 clinical registry platforms from inception to December 2020. Randomized controlled trials involving AT interventions for managing prediabetes were included.

Of the 855 identified trials, 34 articles were included for qualitative synthesis, 31 of which were included in the final meta-analysis. Compared with usual care, sham intervention, or conventional medicine, AT treatments yielded greater reductions in the primary outcomes, including fasting plasma glucose (FPG) (standard mean difference [SMD] = -0.83; 95% confidence interval [CI], -1.06, -0.61; P < .00001), 2-hour plasma glucose (2hPG) (SMD = -0.88; 95% CI, -1.20, -0.57; P < .00001), and glycated hemoglobin (HbA1c) levels (SMD = -0.91; 95% CI, -1.31, -0.51; P < .00001), as well as a greater decline in the secondary outcome, which is the incidence of prediabetes (RR = 1.43; 95% CI, 1.26, 1.63; P < .00001).

The authors concluded that AT is a potential strategy that can contribute to better glycemic control in the management of prediabetes. Because of the substantial clinical heterogeneity, the effect estimates should be interpreted with caution. More research is required for different ethnic groups and long-term effectiveness.

But this is clearly a positive result!

Why do I not believe it?

There are several reasons:

  • There is no conceivable mechanism by which AT prevents diabetes.
  • The findings heavily rely on Chinese RCTs which are known to be of poor quality and often even fabricated. To trust such research would be a dangerous mistake.
  • Many of the primary studies were designed such that they failed to control for non-specific effects of AT. This means that a causal link between AT and the outcome is doubtful.
  • The review was published in a 3rd class journal of no impact. Its peer-review system evidently failed.

So, let’s just forget about this rubbish paper?

If only it were so easy!

Journalists always have a keen interest in exotic treatments that contradict established wisdom. Predictably, they have been reporting about the new review thus confusing or misleading the public. One journalist, for instance, stated:

Acupuncture has been used for thousands of years to treat a variety of illnesses — and now it could also help fight one of the 21st century’s biggest health challenges.

New research from Edith Cowan University has found acupuncture therapy may be a useful tool in avoiding type 2 diabetes.

The team of scientists investigated dozens of studies covering the effects of acupuncture on more than 3600 people with prediabetes. This is a condition marked by higher-than-normal blood glucose levels without being high enough to be diagnosed as diabetes.

According to the findings, acupuncture therapy significantly improved key markers, such as fasting plasma glucose, two-hour plasma glucose, and glycated hemoglobin. Additionally, acupuncture therapy resulted in a greater decline in the incidence of prediabetes.

The review can thus serve as a prime example for demonstrating how irresponsible research has the power to mislead millions. This is why I have often said that poor research is a danger to public health.

And what can be done about this more and more prevalent problem?

The answer is easy: people need to behave more responsibly; this includes:

  • trialists,
  • review authors,
  • editors,
  • peer-reviewers,
  • journalists.

Yes, the answer is easy in theory – but the practice is far from it!

I have often called out unreliable or fraudulent research in the realm of Traditional Chinese Medicine (TCM). I think it is important to do so because the abundance of scientific misconduct is such that it has become a danger to public health. Today, I present yet another example:

This recent review claimed to summarize the evidence on TCM in treating MI, the clinical evaluations of TCM in treating male infertility (MI), and the molecular mechanisms of TCM effects. I was alerted to the fact that the authors cite a paper on acupuncture that I had co-authored. Here is the section in question from the review:

Acupuncture is one of the therapeutic techniques that are part of TCM. Acupuncture is a non-invasive technique and is regarded as free of risk if performed by trained personnel [35]. One of the advantages of acupuncture was that the incidence of adverse effects was substantially lower than that of many drugs or other accepted [35]. Acupuncture has been used in the treatment of male and female infertility and in assisted reproductive technology treatments for many years. A total of 100 patients with MI who met the diagnostic criteria were randomly divided into two groups [7]. Half of the patients received acupuncture treatment, and the other half received placebo acupuncture. After 10 weeks treatment, acupuncture successfully improved the indicators of the semen, including the spermatozoa survival rate, b-level activity rate, sperm density, sperm activity rate. A total of 28 infertile patients with severe oligoasthenozoospermia received acupuncture according to the principles of acupuncture and 29 infertile patients received placebo acupuncture. A significantly higher percentage of motile sperm (World Health Organization categories A-C), but no effect on sperm concentration, was found after acupuncture compared with placebo acupuncture [36]. Of the 279 cases of male sterility treated by the combination of acupuncture, pilose antler essence injection to acupoints and oral administration of Chinese materia medica, 142 cases (47.8%) were cured, 81 cases (27.3%) markedly effective, 53 cases (17.8%) effective and 21 cases (7.1%) ineffective [37]. The therapeutic effect of the combination of these three treatments was satisfactory.

Ref 7

Emerging evidence has shown that cell-cell interactions between testicular cells, in particular at the Sertoli cell-cell and Sertoli-germ cell interface, are crucial to support spermatogenesis. The unique ultrastructures that support cell-cell interactions in the testis are the basal ES (ectoplasmic specialization) and the apical ES. The basal ES is found between adjacent Sertoli cells near the basement membrane that also constitute the blood-testis barrier (BTB). The apical ES is restrictively expressed at the Sertoli-spermatid contact site in the apical (adluminal) compartment of the seminiferous epithelium. These ultrastructures are present in both rodent and human testes, but the majority of studies found in the literature were done in rodent testes. As such, our discussion herein, unless otherwise specified, is focused on studies in testes of adult rats. Studies have shown that the testicular cell-cell interactions crucial to support spermatogenesis are mediated through distinctive signaling proteins and pathways, most notably involving FAK, Akt1/2 and Cdc42 GTPase. Thus, manipulation of some of these signaling proteins, such as FAK, through the use of phosphomimetic mutants for overexpression in Sertoli cell epithelium in vitro or in the testis in vivo, making FAK either constitutively active or inactive, we can modify the outcome of spermatogenesis. For instance, using the toxicant-induced Sertoli cell or testis injury in rats as study models, we can either block or rescue toxicant-induced infertility through overexpression of p-FAK-Y397 or p-FAK-Y407 (and their mutants), including the use of specific activator(s) of the involved signaling proteins against pAkt1/2. These findings thus illustrate that a potential therapeutic approach can be developed to manage toxicant-induced male reproductive dysfunction. In this review, we critically evaluate these recent findings, highlighting the direction for future investigations by bringing the laboratory-based research through a translation path to clinical investigations.

This paper does not relate to the statement it is meant to support by the review authors.

Ref 35

The review by Qin et al (1) includes 5 trials none of which should have been included in a quality metaanalysis as the methodology was unconvincing: In the trial by Alraek et al., patients were randomised to receive either acupuncture or no treatment. This means that no attempt was made to control for the effects of placebo or extra attention. Therefore, this study does not demonstrate an effect of acupuncture as the outcome could be due to non-specific effects unrelated with this therapy. By contrast, the trial by Aune et al. did attempt to control for placebo effects by using a sham control group. Sham acupuncture was given using six needles superficially inserted in the calves, thighs or abdomen outside known acupuncture points or meridians. Needles were not manipulated in the sham group. Sham or placebo controls have the purpose of rendering patients unaware of whether they receive the real or the sham treatment. The method used here cannot achieve this aim; patients would be easily able to tell which intervention they received. In other words, this study also did not adequately control for placebo effects. The remaining three trials are all not Medline-listed, authored by Chinese investigators and published in inaccessible journals. This should disqualify them from inclusion as they were unverifiable by the peer review process. According to the published table, they were equivalence trials of acupuncture versus antibiotics with a sample size around 30. This means they are grossly underpowered and thus unable to generate reliable results. Unless BJOG peer reviewers could see the primary articles, or be provided with translations from Chinese, the systematic review should not have been accepted. The “many eyes of science” requires transparency, testing, challenge and verification. Although in the past, inconclusive results of acupuncture have not been thought to be due to Chinese influence (2), it has been noted that virtually all recent published acupuncture trials are “positive” (3), raising questions of publication and other biases. Our colleagues are under tremendous pressure to publish, but we do them no favours by effectively lowering the standard of scientific peer review. Elite journals too have an obligation to train and reiterate about publication ethics and sound scientific writing (4). As none of the primary studies convincingly demonstrated that acupuncture is an effective therapy for recurrent urinary tract infections, no positive conclusion was warranted. Although Qin et al. did state that the risk of bias of the included trials was generally high or unclear (1), the BJOG nevertheless allowed them to turn massive uncertainty into relatively firm, positive conclusions in the abstract (“Acupuncture appeared to be beneficial for treatment and prophylaxis of rUTIs”) and tweetable abstract (“This review found that acupuncture may improve treatment and prevent recurrence of urinary tract infection in women”), thus leading to excited media headlines that inevitably mislead the public. ‘May’ is a weasel word which should be avoided as it is unfalsifiable (for example, pigs do not fly but they ‘may’ fly in the future). The definite, straightforward conclusion must be “There is no good evidence to support the use of acupuncture for the treatment and prophylaxis of recurrent UTIs”. It is not acceptable to give international credibility to an implausible modality that no objective, independent high-quality review has found effective beyond placebo (5). The dampening accompanying mini-commentary (6) does not undo the damage.
The review should be withdrawn while the primary papers are translated for peer reviewers to examine, the above limitations discussed in the text, and the positive ‘spin’ in conclusions corrected. These improvements would consolidate the researchers’ probity and justify the accolade of BJOG publication.

Our letter to the editor does not bear any relation to the statement it is meant to support by the review authors.

Ref 36

In this first prospective, randomized, single-blind, placebo-controlled study, 28 infertile patients with severe oligoasthenozoospermia received acupuncture according to the principles of traditional Chinese medicine (TCM) and 29 infertile patients received placebo acupuncture. A significantly higher percentage of motile sperm (World Health Organization categories A–C), but no effect on sperm concentration, was found after acupuncture compared with placebo acupuncture.

This small study is far from convincing and does not lend itself to far-reaching conclusions

Ref 37

Of the 279 cases of male sterility treated by the combination of acupuncture, pilose antler
essence injection to acupoints and oral administration of Chinese materia medica, 142
cases (47.8%) were cured, 81 cases (27.3%) markedly effective, 53 cases (17.8%) effective
and 21 cases (7.1%) ineffective. The therapeutic effect of the combination of these three
treatments was satisfactory.

This study had no control group and used two different therapies. Therefore, it does not allow any conclusion about the effectiveness of acupuncture.

____________________

Perhaps you feel that these errors are trivial. But I would disagree. The review authors’ praise of acupuncture for MI is misplaced and will mislead the public. There are plenty of reviews on the subject, and those that are not overtly biased arrive at conclusions like these:

So, how did this sloppy review come about?

Its authors are affiliated to the TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China, and the Tea Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, China. A footnote tells us that their review was supported by the National Natural Science Foundation of China [No. 81973647] and the Xinglin scholar discipline promotion talent program of Chengdu University of traditional Chinese medicine [No. BSH2021018]. This sounds respectable enough.

The journal that published the review is ‘Pharmacological Research – Modern Chinese Medicine‘. Its stated aims are as follows: The journal publishes articles reporting on advances in our comprehension of mechanism and safety in experimental pharmacology and clinical efficacy and safety of pharmacologically active substances, including compound prescriptions, utilized in Traditional Chinese Medicine applying modern scientific research methods. Studies reporting also on the mechanisms of actions of the active substance(s) investigated are encouraged.

The editors in chief of the journal are Guan-Hua Du, PhD, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica, Beijing, China and Emilio Clementi, M.Mus, MD, PhD, University of Milan, Milan, Italy. No doubt, these are respectable scientists. And because they are, they should make sure that what they publish is correct – a criterion this recent review clearly does not meet.

Ischemic heart disease (IHD) related to cardiovascular or cerebrovascular disease is the leading cause of mortality and an important issue of public health worldwide. The cost of long-term healthcare for IHD patients may result in a huge financial burden. This study analyzed the medical expenditure incurred for and survival of IHD patients treated with Chinese herbal medicine (CHM) and Western medicine.

Subjects were randomly selected from the National Health Insurance Research Database in Taiwan. The Cox proportional hazards regression model, Kaplan–Meier estimator, logrank test, chi-square test, and analysis of variance were applied. Landmark analysis was used to assess the cumulative incidence of death in IHD patients.

A total of 11,527 users were identified as CHM combined with Western medicine and 11,527 non-CHM users. CHM users incurred a higher medical expenditure for outpatient care within 1 (24,529 NTD versus 18,464 NTD,  value <0.0001) and 5 years (95,345 NTD versus 60,367 NTD,  value <0.0001). However, CHM users had shorter hospitalizations and lower inpatient medical expenditure (7 days/43,394 NTD in 1 year; 11 days/83,141 NTD in 5 years) than non-CHM users (11 days/72,939 NTD in 1 year; 14 days/107,436 NTD in 5 years).

The CHM group’s adjusted hazard ratio for mortality was 0.41 lower than that of the non-CHM group by Cox proportional hazard models with time-dependent exposure covariates. Danshen, Huang qi, Niu xi, Da huang, and Fu zi were the most commonly prescribed Chinese single herbs; Zhi-Gan-Cao-Tang, Xue-Fu-Zhu-Yu-Tang, Tian-Wang-Bu-Xin-Dan, Sheng-Mai-San, and Yang-Xin-Tang were the five most frequently prescribed herbal formulas in Taiwan.

The authors concluded that combining Chinese and Western medicine can reduce hospital expenditure and improve survival for IHD patients.

Why, you will ask, do I think that this study deserves to be in the ‘worst paper cometition’?

It is not so bad!

It is an epidemiological case-control study with a large sample size that generates interesting findings.

Agreed!

But, as a case-control study, it cannot establish a causal link between CHM and the outcomes. You might argue that the conclusions avoid doing this – “can … improve survival” is not the same as “does improve survival”. This may be true, yet the title of the article leaves little doubt about the interpretation of the authors:

Chinese Herbal Medicine as an Adjunctive Therapy Improves the Survival Rate of Patients with Ischemic Heart Disease: A Nationwide Population-Based Cohort Study

I find it difficult not to view this as a deliberate attempt of the authors, editors, and reviewers to mislead the public.

Looking at the details of the study, it is easy to see that the two groups were different in a whole range of parameters that were measured. More importantly, they most likely differ in a range of variables that were not measured and had significant influence on IHD survival. It stands to reason, for instance, that patients who elected to use CHM in addition to their standard care were more health conscious. They would thus have followed a healthier diet and lifestyle. It would be foolish to claim that such factors do not influence IHD survival.

The fact that the authors fail even to mention this possibility, interpret an association as a causal link, and thus try to mislead us all makes this paper, in my view, a strong contender for my

WORST PAPER OF 2022 COMPETITION

 

 

In 2007, we published a systematic review summarizing the efficacy of homeopathic remedies used as a sole or additional therapy in cancer care. We have searched the literature using the databases: Amed (from 1985); CINHAL (from 1982); EMBASE (from 1974); Medline (from 1951); and CAMbase (from 1998). Randomized and non-randomized controlled clinical trials including patients with cancer or past experience of cancer receiving single or combined homeopathic interventions were included. The methodological quality of the trials was assessed by Jadad score. Six studies met our inclusion criteria (five were randomized clinical trials and one was a non-randomized study); but the methodological quality was variable including some high-standard studies. Our analysis of published literature on homeopathy thus found insufficient evidence to support the clinical efficacy of homeopathic therapy in cancer care.

Meanwhile, more trials have emerged, not least a dubious study by Frass et al which is currently under investigation. This means that a new evaluation of the totality of the available evidence might be called for. I am pleased to report that such an assessment has just been published.

In this systematic review, the researchers included clinical studies from 1800 until 2020 to evaluate evidence of the effectiveness of homeopathy on physical and mental conditions in patients during oncological treatment.

In February 2021 a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsychInfo, CINAHL, and Medline) to find studies concerning the use, effectiveness, and potential harm of homeopathy in cancer patients.

From all 1352 search results, 18 studies with 2016 patients were included in this SR. The patients treated with homeopathy were mainly diagnosed with breast cancer. The therapy concepts include single and combination homeopathic remedies (used systemically or as mouth rinses) of various dilutions. Outcomes assessed were the influence on toxicity of cancer treatment (mostly hot flashes and menopausal symptoms), time to drain-removal in breast cancer patients after mastectomy, survival, quality of life, global health and subjective well-being, anxiety, and depression as well as safety and tolerance.

The included studies reported heterogeneous results: some studies described significant differences in quality of life or toxicity of cancer treatment favoring homeopathy, whereas others did not find an effect or reported significant differences to the disadvantage of homeopathy or side effects caused by homeopathy. The majority of the studies have low methodological quality.

The authors concluded that, for homeopathy, there is neither a scientifically based hypothesis of its mode of action nor conclusive evidence from clinical studies in cancer care.

I predict that, if we wait another 15 years, we will have even more studies. I also predict that some of them will be less than reliable or even fake. Finally, I predict that the overall result will still be mixed and unconvincing.

Why can I be so sure?

  1. Because homeopathy lacks biological plausibility as a treatment of cancer (or any other condition).
  2. Because highly diluted homeopathic remedies are pure placebos.
  3. Because homeopathy has developed into a cult where one is no longer surprised to see studies emerging that are too good to be true.

It seems that no ancient treatment is daft enough for some researchers of so-called alternative medicine (SCAM) to not pick it up. Even bloodletting is back, it seems!

The aim of this study was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. The primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed.

Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs.

The authors concluded that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.

This paper requires a few short comments:

  1. The effect on blood pressure was not ‘minimal’, as the authors pretend, it was non-existent (i.e. not significant and due to chance only).
  2. This lack of effect had to be expected considering human physiology.
  3. The fact that hemoglobin, hematocrit, erythrocytes, and ferritin all change after bloodletting is equally expected.
  4. Mild adverse effects are also no surprise.
  5. What is a surprise, however, that such a trial was ever conducted and passed by an ethics committee. Any medic who has not slept through his/her cardiovascular physiology lectures could have predicted the results quite accurately. And running a trial where the result is well-known before the study has started can hardly be called ethical.

Nausea and vomiting are common symptoms of patients with advanced cancer. While there is some evidence for acupuncture point stimulation in the treatment of these symptoms for patients having anticancer treatment, there is little for when they are not related to such treatment.

This study aimed to determine whether acupressure at the pericardium 6 sites can help treat nausea and vomiting suffered by palliative care patients with advanced cancer. The researchers conducted a double-blind randomized controlled trial-active versus placebo acupressure wristbands. In-patients with advanced cancer in two specialist palliative care units who fitted either or both of the following criteria were approached: nausea that was at least of moderate severity; vomiting daily on average for the prior 3 days.

A total of 57 patients were randomized to have either active or placebo acupressure wristbands. There was no difference in any of the outcome measures between the two groups:

  • change from the baseline number of vomits;
  • Visual Analogue Scale for ‘did acupressure wristbands help you to feel better?’;
  • the total number of doses of antiemetic medication;
  • the need for escalation of antiemetics.

The authors concluded that, in contrast to a previously published feasibility study, active acupressure wristbands were no better than placebo for specialist palliative care in patients with advanced cancer and nausea and vomiting.

When the research into acupuncture for nausea and vomiting began some 20 years ago, the evidence turned out to be encouraging. Later, as the studies became more and more rigorous, many trials failed to confirm the initial findings. Today, the totality of the evidence is far less convincing than it seemed years ago.

This is a phenomenon that can be observed not just in acupuncture research but in many types of treatment:

  • Initially, over-enthusiastic researchers become victims of their own optimism.
  • These investigators are less into testing hypotheses than into confirming their own wishful thinking.
  • Thus, several positive trials emerge.
  • These, however, turn out to be methodologically flawed.
  • Eventually, the subject might be picked up by real scientists who truly test hypotheses.
  • More and more negative studies thus emerge.
  • Depending on how many flawed studies were initially published and how critical the authors of systematic reviews are, it can take years until the totality of the evidence depicts the true picture which discloses the initial findings as false-positive.

The message is, I think, clear: poor quality studies have the potential to mislead us for many years. Eventually, however, the self-cleansing ability of science should generate the truth about the value of any treatment. In other words:

poor-quality science is not just useless, it causes long-term harm

and

critical thinking prevents harm

 

Alan Gaby, the assistant editor of the journal Integr Med has written an interesting commentary about widespread fraud in natural health products research. Here is an excerpt of his article:

During the past 49 years, I have reviewed and analyzed more than 50 000 papers from the biomedical literature, most of which were related to the field of nutritional medicine. Doing this work has given me some understanding of how to assess the reliability of a study. Over the past 10 to 15 years, an uncomfortably large and growing number of published papers related to my area of expertise have left me wondering whether the research was fabricated; that is, whether people were writing papers about research that had not actually been conducted. If the studies were not actually conducted, the publishing of this research is an affront to all who value integrity in science, and it has the potential to harm practitioners and patients who rely on its findings.

The studies that have raised concerns have come primarily from Iran and to a lesser extent from Egypt, China, India, Japan, and a few other countries. Characteristics of these concerning studies typically include one or more of the following:

  1. The study comes from an investigator or research group that has published an enormous number of randomized clinical trials in a relatively short period of time.
  2. The number of participants in the trial is unusually large, when considering the resources that appear to be available to the researchers.
  3. The recruitment period for the trial is unusually short.
  4. The paper is submitted to a journal unusually rapidly after the study is completed, or in some cases before it would have been possible to have completed the trial.
  5. A randomized double-blind trial is conducted before there is any preliminary evidence of efficacy in humans (such as case reports or uncontrolled trials). Because double-blind trials are expensive to conduct, such trials are generally reserved for treatments for which there is some evidence of efficacy.
  6. The magnitude of the reported improvement is much larger than is typically seen in trials using just one or two nutrients.
  7. No funding source is listed or the study is listed as self-funded. This is of particular concern when the sample size or study design suggests that the study was expensive.
  8. The design of the study raises ethical issues, such as participants not being permitted to use treatments that are known to be effective.
  9. One or more baseline characteristics of the study group appear to be implausible.
  10. The research was conducted by a student as part of a graduate school thesis, and the magnitude of the project seems to have been beyond the capabilities and resources of a student.

__________________________________

What Gaby alludes to is a problem indeed. I have previously posted about the Chinese aspect of this story. What Gaby does not mention is the fact that even many studies of so-called alternative medicine (SCAM) which seem to be not overtly fraudulent are nevertheless highly suspect. I am referring to trials that are fatally flawed and/or studies that draw unwarranted conclusions. These are, of course, the types of studies that are the main target of this blog. Because they are so numerous, I feel that the damage they do is much bigger than that of the more overtly fraudulent papers.

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