scientific misconduct
Sure, the LP is dangerous nonsense, but this begs the question of whether so-called alternative medicine (SCAM) has anything to offer for patients suffering from ME/CFS. If the LP story tells us anything, then it must be this: we should not trust single trials, particularly if they seem dodgy. In other words, we should look at systematic reviews that synthesize ALL clinical trials and evaluate them critically.
To locate this type of evidence I conducted several Medline searches and found several recent systematic reviews that address the issue:
Context: A variety of interventions have been used in the treatment and management of chronic fatigue syndrome (CFS). Currently, debate exists among health care professionals and patients about appropriate strategies for management.
Objective: To assess the effectiveness of all interventions that have been evaluated for use in the treatment or management of CFS in adults or children.
Data sources: Nineteen specialist databases were searched from inception to either January or July 2000 for published or unpublished studies in any language. The search was updated through October 2000 using PubMed. Other sources included scanning citations, Internet searching, contacting experts, and online requests for articles.
Study selection: Controlled trials (randomized or nonrandomized) that evaluated interventions in patients diagnosed as having CFS according to any criteria were included. Study inclusion was assessed independently by 2 reviewers. Of 350 studies initially identified, 44 met inclusion criteria, including 36 randomized controlled trials and 8 controlled trials.
Data extraction: Data extraction was conducted by 1 reviewer and checked by a second. Validity assessment was carried out by 2 reviewers with disagreements resolved by consensus. A qualitative synthesis was carried out and studies were grouped according to type of intervention and outcomes assessed.
Data synthesis: The number of participants included in each trial ranged from 12 to 326, with a total of 2801 participants included in the 44 trials combined. Across the studies, 38 different outcomes were evaluated using about 130 different scales or types of measurement. Studies were grouped into 6 different categories. In the behavioral category, graded exercise therapy and cognitive behavioral therapy showed positive results and also scored highly on the validity assessment. In the immunological category, both immunoglobulin and hydrocortisone showed some limited effects but, overall, the evidence was inconclusive. There was insufficient evidence about effectiveness in the other 4 categories (pharmacological, supplements, complementary/alternative, and other interventions).
Conclusions: Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded exercise therapy. Further research into these and other treatments is required using standardized outcome measures.
Introduction: Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.
Methods and outcomes: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results: We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.
Background: Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population.
Methods: Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded.
Results: A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium.
Conclusions: The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.
Background: There is no curative treatment for chronic fatigue syndrome (CFS). Traditional Chinese medicine (TCM) is widely used in the treatment of CFS in China.
Objective: To evaluate the effectiveness and safety of TCM for CFS.
Methods: The protocol of this review is registered at PROSPERO. We searched six main databases for randomized clinical trials (RCTs) on TCM for CFS from their inception to September 2013. The Cochrane risk of bias tool was used to assess the methodological quality. We used RevMan 5.1 to synthesize the results.
Results: 23 RCTs involving 1776 participants were identified. The risk of bias of the included studies was high. The types of TCM interventions varied, including Chinese herbal medicine, acupuncture, qigong, moxibustion, and acupoint application. The results of meta-analyses and several individual studies showed that TCM alone or in combination with other interventions significantly alleviated fatigue symptoms as measured by Chalder’s fatigue scale, fatigue severity scale, fatigue assessment instrument by Joseph E. Schwartz, Bell’s fatigue scale, and guiding principle of clinical research on new drugs of TCM for fatigue symptom. There was no enough evidence that TCM could improve the quality of life for CFS patients. The included studies did not report serious adverse events.
Conclusions: TCM appears to be effective to alleviate the fatigue symptom for people with CFS. However, due to the high risk of bias of the included studies, larger, well-designed studies are needed to confirm the potential benefit in the future.
Background: As the etiology of chronic fatigue syndrome (CFS) is unclear and the treatment is still a big issue. There exists a wide range of literature about acupuncture and moxibustion (AM) for CFS in traditional Chinese medicine (TCM). But there are certain doubts as well in the effectiveness of its treatment due to the lack of a comprehensive and evidence-based medical proof to dispel the misgivings. Current study evaluated systematically the effectiveness of acupuncture and moxibustion treatments on CFS, and clarified the difference among them and Chinese herbal medicine, western medicine and sham-acupuncture.
Methods: We comprehensively reviewed literature including PubMed, EMBASE, Cochrane library, CBM (Chinese Biomedical Literature Database) and CNKI (China National Knowledge Infrastructure) up to May 2016, for RCT clinical research on CFS treated by acupuncture and moxibustion. Traditional direct meta-analysis was adopted to analyze the difference between AM and other treatments. Analysis was performed based on the treatment in experiment and control groups. Network meta-analysis was adopted to make comprehensive comparisons between any two kinds of treatments. The primary outcome was total effective rate, while relative risks (RR) and 95% confidence intervals (CI) were used as the final pooled statistics.
Results: A total of 31 randomized controlled trials (RCTs) were enrolled in analyses. In traditional direct meta-analysis, we found that in comparison to Chinese herbal medicine, CbAM (combined acupuncture and moxibustion, which meant two or more types of acupuncture and moxibustion were adopted) had a higher total effective rate (RR (95% CI), 1.17 (1.09 ~ 1.25)). Compared with Chinese herbal medicine, western medicine and sham-acupuncture, SAM (single acupuncture or single moxibustion) had a higher total effective rate, with RR (95% CI) of 1.22 (1.14 ~ 1.30), 1.51 (1.31-1.74), 5.90 (3.64-9.56). In addition, compared with SAM, CbAM had a higher total effective rate (RR (95% CI), 1.23 (1.12 ~ 1.36)). In network meta-analyses, similar results were recorded. Subsequently, we ranked all treatments from high to low effective rate and the order was CbAM, SAM, Chinese herbal medicine, western medicine and sham-acupuncture.
Conclusions: In the treatment of CFS, CbAM and SAM may have better effect than other treatments. However, the included trials have relatively poor quality, hence high quality studies are needed to confirm our finding.
Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS). Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software. Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: -1.77; 95%CI: -1.96 to -1.57; p < 0.001), Fatigue Assessment Instrument scores (WMD: -15.75; 95%CI: -26.89 to -4.61; p < 0.01), Self-Rating Scale of mental state scores (WMD: -9.72; 95%CI:-12.26 to -7.18; p < 0.001), Self-Rating Anxiety Scale scores (WMD: -7.07; 95%CI: -9.96 to -4.19; p < 0.001), Self-Rating Depression Scale scores (WMD: -5.45; 95%CI: -6.82 to -4.08; p < 0.001), and clinical symptom scores (WMD: -5.37; 95%CI: -6.13 to -4.60; p < 0.001) and improve IGA (WMD: 0.30; 95%CI: 0.20-0.41; p < 0.001), IGG (WMD: 1.74; 95%CI: 0.87-2.62; p < 0.001), IGM (WMD: 0.21; 95%CI: 0.14-0.29; p < 0.001), and the effective rate (RR = 1.41; 95%CI: 1.33-1.49; p < 0.001). However, natural killer cell levels did not change significantly. The included studies did not report any serious adverse events. In addition, the methodology quality of the included RCTs was generally not high. Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research.
What does all that tell us?
Disappointingly, it tells me that SCAM has preciously little to offer for ME/CFS patients.
But what about the TCM treatments? Aren’t the above reviews quite positive TCM?
Yes, they are but I nevertheless recommend taking them with a healthy pinch of salt.
Why?
Because we have seen many times before that, for a range of reasons, Chinese researchers of TCM draw false positive conclusions. That may sound unfair, harsh, or even racist, but I think it’s true. If you disagree, please show me a couple of systematic reviews of TCM for any human disease by Chinese researchers that have drawn negative conclusions.
And what is my advice to patients suffering from ME/CSF?
I think the best I can offer is this: be very cautious about the many claims made by SCAM enthusiasts; if it sounds too good to be true, it probably is!
In this study, the impact of a multimodal integrative oncology pre- and intraoperative intervention on pain and anxiety among patients undergoing gynecological oncology surgery was explored.
Study participants were randomized into three groups:
- Group A received preoperative touch/relaxation techniques, followed by intraoperative acupuncture, plus standard care;
- Group B received preoperative touch/relaxation only, plus standard care;
- Group C (the control group) received standard care.
Pain and anxiety were scored before and after surgery using the Measure Yourself Concerns and Wellbeing (MYCAW) and Quality of Recovery (QOR-15) questionnaires, using Part B of the QOR to assess pain, anxiety, and other quality-of-life parameters.
A total of 99 patients participated in the study: 45 in Group A, 25 in Group B, and 29 in Group C. The three groups had similar baseline demographic and surgery-related characteristics. Postoperative QOR-Part B scores were significantly higher in the treatment groups (A and B) when compared with controls (p = .005), including for severe pain (p = .011) and anxiety (p = .007). Between-group improvement for severe pain was observed in Group A compared with controls (p = .011). Within-group improvement for QOR depression subscales was observed in only the intervention groups (p <0.0001). Compared with Group B, Group A had better improvement of MYCAW-reported concerns (p = .025).
The authors concluded that a preoperative touch/relaxation intervention may significantly reduce postoperative anxiety, possibly depression, in patients undergoing gynecological oncology surgery. The addition of intraoperative acupuncture significantly reduced severe pain when compared with controls. Further research is needed to confirm these findings and better understand the impact of intraoperative acupuncture on postoperative pain.
Regular readers of my blog know only too well what I am going to say about this study.
Imagine you have a basket full of apples and your friend has the same plus a basket full of pears. Who do you think has more fruit?
Dumb question, you say?
Correct!
Just as dumb, it seems, as this study: therapy A and therapy B will always generate better outcomes than therapy B alone. But that does not mean that therapy A per se is effective. Because therapy A generates a placebo effect, it might just be that it has no effect beyond placebo. And that acupuncture can generate placebo effects has been known for a very long time; to verify this we need no RCT.
As I have so often pointed out, the A+B versus B study design never generates a negative finding.
This is, I fear, precisely the reason why this design is so popular in so-called alternative medicine (SCAM)! It enables promoters of SCAM (who are not as dumb as the studies they conduct) to pretend they are scientists testing their therapies in rigorous RCTs.
The most disappointing thing about all this is perhaps that more and more top journals play along with this scheme to mislead the public!
The purpose of this review was to
- identify and map the available evidence regarding the effectiveness and harms of spinal manipulation and mobilisation for infants, children and adolescents with a broad range of conditions;
- identify and synthesise policies, regulations, position statements and practice guidelines informing their clinical use.
Two reviewers independently screened and selected the studies, extracted key findings and assessed the methodological quality of included papers. A descriptive synthesis of reported findings was undertaken using a level-of-evidence approach.
Eighty-seven articles were included. Their methodological quality varied. Spinal manipulation and mobilisation are being utilised clinically by a variety of health professionals to manage paediatric populations with 
- adolescent idiopathic scoliosis (AIS),
- asthma,
- attention deficit hyperactivity disorder (ADHD),
- autism spectrum disorder (ASD),
- back/neck pain,
- breastfeeding difficulties,
- cerebral palsy (CP),
- dysfunctional voiding,
- excessive crying,
- headaches,
- infantile colic,
- kinetic imbalances due to suboccipital strain (KISS),
- nocturnal enuresis,
- otitis media,
- torticollis,
- plagiocephaly.
The descriptive synthesis revealed: no evidence to explicitly support the effectiveness of spinal manipulation or mobilisation for any condition in paediatric populations. Mild transient symptoms were commonly described in randomised controlled trials and on occasion, moderate-to-severe adverse events were reported in systematic reviews of randomised controlled trials and other lower-quality studies. There was strong to very strong evidence for ‘no significant effect’ of spinal manipulation for managing
- asthma (pulmonary function),
- headache,
- nocturnal enuresis.
There was inconclusive or insufficient evidence for all other conditions explored. There is insufficient evidence to draw conclusions regarding spinal mobilisation to treat paediatric populations with any condition.
The authors concluded that, whilst some individual high-quality studies demonstrate positive results for some conditions, our descriptive synthesis of the collective findings does not provide support for spinal manipulation or mobilisation in paediatric populations for any condition. Increased reporting of adverse events is required to determine true risks. Randomised controlled trials examining effectiveness of spinal manipulation and mobilisation in paediatric populations are warranted.
Perhaps the most important findings of this review relate to safety. They confirm (yet again) that there is only limited reporting of adverse events in this body of research. Six reviews, eight RCTs and five other studies made no mention of adverse events or harms associated with spinal manipulation. This, in my view, amounts to scientific misconduct. Four systematic reviews focused specifically on adverse events and harms. They revealed that adverse events ranged from mild to severe and even death.
In terms of therapeutic benefit, the review confirms the findings from the previous research, e.g.:
- Green et al (Green S, McDonald S, Murano M, Miyoung C, Brennan S. Systematic review of spinal manipulation in children: review prepared by Cochrane Australia for Safer Care Victoria. Melbourne, Victoria: Victorian Government 2019. p. 1–67.) explored the effectiveness and safety of spinal manipulation and showed that spinal manipulation should – due to a lack of evidence and potential risk of harm – be recommended as a treatment of headache, asthma, otitis media, cerebral palsy, hyperactivity disorders or torticollis.
- Cote et al showed that evidence is lacking to support the use of spinal manipulation to treat non-musculoskeletal disorders.
In terms of risk/benefit balance, the conclusion could thus not be clearer: no matter whether chiropractors, osteopaths, physiotherapists, or any other healthcare professionals propose to manipulate the spine of your child, DON’T LET THEM DO IT!
Didier Raoult, the French scientist who became well-known for his controversial stance on hydroxychloroquine for treating COVID-19, has featured on this blog before (see here, here, and here). Less well-known is the fact that he has attracted controversy before. In 2006, Raoult and 4 co-authors were banned for one year from publishing in the journals of the American Society for Microbiology (ASM), after a reviewer for Infection and Immunity discovered that four figures from the revised manuscript of a paper about a mouse model for typhus were identical to figures from the originally submitted manuscript, even though they were supposed to represent a different experiment. In response, Raoult “resigned from the editorial board of two other ASM journals, canceled his membership in the American Academy of Microbiology, ASM’s honorific leadership group, and banned his lab from submitting to ASM journals”. In response to Science covering the story in 2012, he stated that, “I did not manage the paper and did not even check the last version”. The paper was subsequently published in a different journal.
Now, the publisher PLOS is marking nearly 50 articles by Didier Raoult, with expressions of concern while it investigates potential research ethics violations in the work. PLOS has been looking into more than 100 articles by Raoult and determined that the issues in 49 of the papers, including reuse of ethics approval reference numbers, warrant expressions of concern while the publisher continues its inquiry.
In August of 2021, Elisabeth Bik wrote on her blog about a series of 17 articles from IHU-Méditerranée Infection that described different studies involving homeless people in Marseille over a decade, but all listed the same institutional ethics approval number. Bik and other commenters on PubPeer have identified ethical concerns in many other papers, including others in large groups of papers with the same ethical approval numbers. Subsequently, Bik has received harassment and legal threats from Raoult.
David Knutson, senior manager of communications for PLOS, sent ‘Retraction Watch’ this statement:
PLOS is issuing interim Expressions of Concerns for 49 articles that are linked to researchers affiliated with IHU-Méditerranée Infection (Marseille, France) and/or the Aix-Marseille University, as part of an ongoing case that involves more than 100 articles in total. Many of the papers in this case include controversial scientist Didier Raoult as a co-author.
Several whistleblowers raised concerns about articles from this institute, including that several ethics approval reference numbers have been reused in many articles. Our investigation, which has been ongoing for more than a year, confirmed ethics approval reuse and also uncovered other issues including:
- highly prolific authorship (a rate that would equate to nearly 1 article every 3 days for one or more individuals), which calls into question whether PLOS’ authorship criteria have been met
- undeclared COIs with pharmaceutical companies
To date, PLOS has completed a detailed initial assessment of 108 articles in total and concluded that 49 warrant an interim Expression of Concern due to the nature of the concerns identified. We’ll be following up with the authors of all articles of concern in accordance with COPE guidance and PLOS policies, but we anticipate it will require at least another year to complete this work.
Raoult is a coauthor on 48 of the 49 papers in question. This summer, Raoult retired as director of IHU-Méditerranée Infection, the hospital and research institution in Marseille that he had overseen since 2011, following an inspection by the French National Agency for the Safety of Medicines and Health Products (ANSM) that found “serious shortcomings and non-compliances with the regulations for research involving the human person” at IHU-Méditerranée Infection and another Marseille hospital. ANSM imposed sanctions on IHU-Méditerranée Infection, including suspending a research study and placing any new research involving people under supervision, and called for a criminal investigation. Other regulators have also urged Marseille’s prosecutor to investigate “serious malfunctions” at the research institution.
Pierre-Edouard Fournier, the new director of IHU-Méditerranée Infection, issued a statement on September 7th that said he had “ensured that all clinical trials in progress relating to research involving the human person (RIPH) were suspended pending the regularization of the situation.” Also in September, the American Society for Microbiology placed expressions of concern on 6 of Raoult’s papers in two of its journals, citing “a ‘scientific misconduct investigation’ by the University of Aix Marseille,” where the researcher also has an affiliation.
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Christian Lehman predicted on my blog that ” If Covid19 settles in the long-term, he [Raoult] will not be able to escape a minutely detailed autopsy of his statements and his actions. And the result will be devastating.” It seems he was correct.
Osteopathy is currently regulated in 12 European countries: Cyprus, Denmark, Finland, France, Iceland, Italy, Liechtenstein, Luxembourg, Malta, Portugal, Switzerland, and the UK. Other countries such as Belgium and Norway have not fully regulated it. In Austria, osteopathy is not recognized or regulated. The Osteopathic Practitioners Estimates and RAtes (OPERA) project was developed as a Europe-based survey, whereby an updated profile of osteopaths not only provides new data for Austria but also allows comparisons with other European countries.
A voluntary, online-based, closed-ended survey was distributed across Austria in the period between April and August 2020. The original English OPERA questionnaire, composed of 52 questions in seven sections, was translated into German and adapted to the Austrian situation. Recruitment was performed through social media and an e-based campaign.
The survey was completed by 338 individuals (response rate ~26%), of which 239 (71%) were female. The median age of the responders was 40–49 years. Almost all had preliminary healthcare training, mainly in physiotherapy (72%). The majority of respondents were self-employed (88%) and working as sole practitioners (54%). The median number of consultations per week was 21–25 and the majority of respondents scheduled 46–60 minutes for each consultation (69%).
The most commonly used diagnostic techniques were: palpation of position/structure, palpation of tenderness, and visual inspection. The most commonly used treatment techniques were cranial, visceral, and articulatory/mobilization techniques. The majority of patients estimated by respondents consulted an osteopath for musculoskeletal complaints mainly localized in the lumbar and cervical region. Although the majority of respondents experienced a strong osteopathic identity, only a small proportion (17%) advertise themselves exclusively as osteopaths.
The authors concluded that this study represents the first published document to determine the characteristics of the osteopathic practitioners in Austria using large, national data. It provides new information on where, how, and by whom osteopathic care is delivered. The information provided may contribute to the evidence used by stakeholders and policy makers for the future regulation of the profession in Austria.
This paper reveals several findings that are, I think, noteworthy:
- Visceral osteopathy was used often or very often by 84% of the osteopaths.
- Muscle energy techniques were used often or very often by 53% of the osteopaths.
- Techniques applied to the breasts were used by 59% of the osteopaths.
- Vaginal techniques were used by 49% of the osteopaths.
- Rectal techniques were used by 39% of the osteopaths.
- “Taping/kinesiology tape” was used by 40% of osteopaths.
- Applied kinesiology was used by 17% of osteopaths and was by far the most-used diagnostic approach.
Perhaps the most worrying finding of the entire paper is summarized in this sentence: “Informed consent for oral techniques was requested only by 10.4% of respondents, and for genital and rectal techniques by 21.0% and 18.3% respectively.”
I am lost for words!
I fail to understand what meaningful medical purpose the fingers of an osteopath are supposed to have in a patient’s vagina or rectum. Surely, putting them there is a gross violation of medical ethics.
Considering these points, I find it impossible not to conclude that far too many Austrian osteopaths practice treatments that are implausible, unproven, potentially harmful, unethical, and illegal. If patients had the courage to take action, many of these charlatans would probably spend some time in jail.
An international team of researchers described retracted papers originating from paper mills, including their characteristics, visibility, and impact over time, and the journals in which they were published. The term paper mill refers to for-profit organizations that engage in the large-scale production and sale of papers to researchers, academics, and students who wish to, or have to, publish in peer-reviewed journals. Many paper mill papers included fabricated data.
All paper mill papers retracted from 1 January 2004 to 26 June 2022 were included in the study. Papers bearing an expression of concern were excluded. Descriptive statistics were used to characterize the sample and analyze the trend of retracted paper mill papers over time, and to analyze their impact and visibility by reference to the number of citations received.
In total, 1182 retracted paper mill papers were identified. The publication of the first paper mill paper was in 2004 and the first retraction was in 2016; by 2021, paper mill retractions accounted for 772 (21.8%) of the 3544 total retractions. Overall, retracted paper mill papers were mostly published in journals of the second highest Journal Citation Reports quartile for impact factor (n=529 (44.8%)) and listed four to six authors (n=602 (50.9%)). Of the 1182 papers, almost all listed authors of 1143 (96.8%) paper mill retractions came from Chinese institutions, and 909 (76.9%) listed a hospital as a primary affiliation. 15 journals accounted for 812 (68.7%) of 1182 paper mill retractions, with one journal accounting for 166 (14.0%). Nearly all (n=1083, 93.8%) paper mill retractions had received at least one citation since publication, with a median of 11 (interquartile range 5-22) citations received.
The authors concluded that papers retracted originating from paper mills are increasing in frequency, posing a problem for the research community. Retracted paper mill papers most commonly originated from China and were published in a small number of journals. Nevertheless, detected paper mill papers might be substantially different from those that are not detected. New mechanisms are needed to identify and avoid this relatively new type of misconduct.
China encourages its researchers to publish papers in return for money and career promotions. Furthermore, medical students at Chinese universities are required to produce a scientific paper in order to graduate. Paper mills openly advertise their services on the Internet and maintain a presence on university campuses. The authors of this analysis reference another recent article (authored by two Chinese researchers) that throws more light on the problem:
This study used data from the Retraction Watch website and from published reports on retractions and paper mills to summarize key features of research misconduct in China. Compared with publicized cases of falsified or fabricated data by authors from other countries of the world, the number of Chinese academics exposed for research misconduct has increased dramatically in recent years. Chinese authors do not have to generate fake data or fake peer reviews for themselves because paper mills in China will do the work for them for a price. Major retractions of articles by authors from China were all announced by international publishers. In contrast, there are few reports of retractions announced by China’s domestic publishers. China’s publication requirements for physicians seeking promotions and its leniency toward research misconduct are two major factors promoting the boom of paper mills in China.
As the authors of the new analysis point out: “Fraudulent papers have negative consequences for the scientific community and the general public, engendering distrust in science, false claims of drug or device efficacy, and unjustified academic promotion, among other problems.” On this blog, I have often warned of research originating from China (some might even think that this is becoming an obsession of mine but I do truly think that this is very important). While such fraudulent papers may have a relatively small impact in many areas of healthcare, their influence in the realm of TCM (where the majority of research comes from China) is considerable. In other words, TCM research is infested by fraud to a degree that prevents drawing meaningful conclusions about the value of TCM treatments.
I feel strongly that it is high time for us to do something about this precarious situation. Otherwise, I fear that in the near future no respectable scientist will take TCM seriously.
The U.S. Food and Drug Administration issued warning letters to seven companies for illegally selling dietary supplements that claim to cure, treat, mitigate or prevent cardiovascular disease or related conditions, such as atherosclerosis, stroke or heart failure, in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The FDA is urging consumers not to use these or similar products because they have not been evaluated by the FDA to be safe or effective for their intended use and may be harmful.
The warning letters were issued to:
- Essential Elements (Scale Media Inc.);
- Calroy Health Sciences LLC;
- Iwi;
- BergaMet North America LLC;
- Healthy Trends Worldwide LLC (Golden After 50);
- Chambers’ Apothecary;
- Anabolic Laboratories, LLC.
“Given that cardiovascular disease is the leading cause of death in the U.S., it’s important that the FDA protect the public from products and companies that make unlawful claims to treat it. Dietary supplements that claim to cure, treat, mitigate or prevent cardiovascular disease and related conditions could potentially harm consumers who use these products instead of seeking safe and effective FDA-approved treatments from qualified health care providers,” said Cara Welch, Ph.D., director of the Office of Dietary Supplement Programs in the FDA’s Center for Food Safety and Applied Nutrition. “We encourage consumers to remain vigilant when shopping online or in stores to avoid purchasing products that could put their health at risk.”
Under the FD&C Act, products intended to diagnose, cure, treat, mitigate or prevent disease are drugs and are subject to the requirements that apply to drugs, even if they are labeled as dietary supplements. Unlike drugs approved by the FDA, the agency has not evaluated whether the unapproved products subject to the warning letters announced today are effective for their intended use, what the proper dosage might be, how they could interact with FDA-approved drugs or other substances, or whether they have dangerous side effects or other safety concerns.
The FDA advises consumers to talk to their doctor, pharmacist or other health care provider before deciding to purchase or use any dietary supplement or drug. Some supplements might interact with medicines or other supplements. Health care providers will work with patients to determine which treatment is the best option for their condition.
If a consumer thinks that a product might have caused a reaction or an illness, they should immediately stop using the product and contact their health care provider. The FDA encourages health care providers and consumers to report any adverse reactions associated with FDA-regulated products to the agency using MedWatch or the Safety Reporting Portal.
The FDA has requested responses from the companies within 15 working days stating how they will address the issues described in the warning letters or provide their reasoning and supporting information as to why they think the products are not in violation of the law. Failure to correct violations promptly may result in legal action, including product seizure and/or injunction.
It has been reported that the Regional Court of Dortmund has prohibited the manufacturer of the homeopathic cold remedy Meditonsin from advertising with false health claims. The court did not see sufficient evidence for the advertising claims.
The Consumer Advice Centre (VZ) of North Rhine-Westphalia issued a warning to the Meditonsin manufacturer (MEDICE Arzneimittel Pütter GmbH & Co.) for misleading advertising statements and sued them. The complaint was:
- that the advertising gave the false impression that an improvement in health could be expected with certainty after taking the product,
- that no side effects were to be expected,
- that the product was superior to “chemical-synthetic medicines”.
The Dortmund Regional Court was not convinced by a study referred to by the manufacturer. On its website, the manufacturer of Meditonsin presents the results of a “current, large-scale user study with more than 1,000 patients” under the heading “Proven efficacy & tolerability”. According to a pie chart, 90% of the patients were satisfied or very satisfied with the effect of Meditonsin.
However, according to the VZ, the study was only a “pharmacy-based observational study” with little scientific validity. Despite the lack of evidence, the manufacturer claimed that “the good efficacy and tolerability of Meditonsin® Drops could once again be impressively confirmed”. The Dortmund Regional Court, however, followed the VZ’s statement of grounds for action. “It is not allowed to advertise with statements that give the false impression that a successful treatment can be expected with certainty, as the advertisement for Meditonsin drops suggests,” emphasized Gesa Schölgens, head of “Faktencheck Gesundheitswerbung”, a joint project of the consumer centres of North Rhine-Westphalia and Rhineland-Palatinate. According to the Therapeutic Products Advertising Act, this is prohibited.
The Dortmund Regional Court also found that consumers were misled by the advertising because it gave a false impression that no harmful side effects were to be expected when taking Meditonsin. The package leaflet of the drug listed several side effects. According to this, there could even be an initial worsening of the symptoms after taking the medicine.
According to the VZ, the alleged advantage of the “natural medicinal product” over “many chemical-synthetic medicinal products that only suppress the symptoms”, as presented by the manufacturer, is also inadmissible. This is because it is not permissible to advertise to consumers with claims that the effect is equivalent or superior to that of another medicinal product. This, too, was confirmed by the court.
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In case you like to know more about the remedy, this is from its English language site:
Meditonsin consists of Aconitum, Atropinum Sulfuricum, Mercurius Cyanatus. Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease.
Guest post by Norbert Aust and Viktor Weisshäupl
Readers of this blog may remember the recent study of Frass et al. about the adjunct homeopathic treatment of patients suffering from non-small cell lung cancer (here). It was published in 2020 by the ‘Oncologist’, a respectable journal, and came to stunning results about to the effectiveness of homeopathy.
In our analysis, however, we found strong indications for duplicity: important study parameters like exclusion criteria or observation time were modified post hoc, and data showed characteristics that occur when unwanted data sets get removed.
We, that is the German Informationsnetzwerk Homöopathie and the Austrian ‘Initiative für wissenschaftliche Medizin’, had informed the Medical University Vienna about our findings – and the research director then asked the Austrian Agency for Scientific Integrity (OeAWI) to review the paper. The analysis took some time and included not only the paper and publicly available information but also the original data. In the end, OeAWI corroborated our findings: The results are not based on sound research but on modified or falsified data.
Here is their conclusion in full:
The committee concludes that there are numerous breaches of scientific integrity in the Study, as reported in the Publication. Several of the results can only be explained by data manipulation or falsification. The Publication is not a fair representation of the Study. The committee cannot for all the findings attribute the wrongdoings and incorrect representation to a single individual. However following our experience it is highly unlikely that the principal investigator and lead author, but also the co-authors were unaware of the discrepancies between the protocols and the Publication, for which they bear responsibility. (original English wording)
Profil, the leading news magazine of Austria reported in its issue of October 24, 2022, pp 58-61 (in German). There the lead author, Prof. M. Frass, a member of Edzard’s alternative medicine hall of fame, was asked for his comments. Here is his concluding statement:
All the allegations are known to us and completely incomprehensible, we can refute all of them. Our work was performed observing all scientific standards. The allegation of breaching scientific integrity is completely unwarranted. To us, it is evident that not all documents were included in the analysis of our study. Therefore we requested insight into the records to learn about the basis for the final statement.
(Die Vorwürfe sind uns alle bekannt und absolut unverständlich, alle können wir entkräften. Unsere Arbeit wurde unter Einhaltung aller wissenschaftlichen Standards durchgeführt. Der Vorhalt von Verstößen gegen die wissenschaftliche Intergrität enbehrt jeder Grundlage. Für uns zeigt sich offenkundig, dass bei der Begutachtung unserer Studie nicht alle Unterlagen miteinbezogen wurden. Aus diesem Grunde haben wir um Akteneinsicht gebeten, um die Grundlagen für das Final Statment kennenzulernen.)
The OeAWI together with the Medical University Vienna asked the ‘Oncologist’ for a retraction of this paper – which has not occurred as yet.
This randomized clinical trial (RCT) tested whether acupuncture is effective for the prevention of chronic tension-type headaches (CTTH). The researchers recruited 218 participants who were diagnosed with CTTH.
- The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes.
- The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)—defined as a type of sham control by avoiding deqi sensation at each acupuncture site.
The main outcome measure was the responder rate at 16 weeks after randomization. Followed-up was 32 weeks. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs).
The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group.
The authors concluded that the 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment.
“Our study showed that deqi sensation could enhance the effect of acupuncture in the treatment of chronic TTH, and the effect of acupuncture lasted at least 6 months when the treatment was stopped,” said co-investigator Ying Li, MD, PhD, The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Why am I not convinced?
Assuming that all the findings are correctly reported, the study does not at all show that the treatment was effective. It merely demonstrates that those patients who knew that were receiving TA told the researcher that they improved more than those who knew they has sham acupuncture. The difference in outcomes is not in the least surprising: patients’ knowledge of having had the verum leads to a placebo effect and to social desirability (patients giving the researchers positive responses simply because they were thankful for being looked after). Patients’ knowledge of having had the sham treatment leads to disappointment and thus worse outcomes.
But this is not the only reason why I am skeptical about this study. The authors claim they achieved deqi at every treatment. That is 20 treatments in 110 patients or 2 200 deqis! I think someone might be telling porkies here. Deqi cannot reliably be elicited on every single occasion. I, therefore, feel that perhaps the authors of this trial were a bit more than generous when writing up their study, and I am reminded of the recent report claiming that more than 80% of clinical trial data from China are fabricated.
