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- Alexander Y PanchinPublished on: 4 February 2019
- Sergey TarasovPublished on: 25 December 2018
- Published on: 4 February 2019Re: Defamation: no evidence required
- Alexander Y Panchin, senior researcher Sector of Molecular Evolution, Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia
Sergey Tarasov responded to our article “Drug discovery today: no molecules required” with claims of mistakes in our analysis. We are sure that we did not conceal anything of relevance or make any mistakes. This is a response to the claims by Sergey Tarasov.
1. Tarasov claims that one of us has an undeclared conflict of interest: “However, one of the authors of the article, Khromov-Borisov NN, is a defendant in a defamation lawsuit brought by Materia Medica (June 28, 2018). Materia Medica has sued Khromov-Borisov NN <…> this therefore raises serious doubts over the objectivity and impartiality of one of the authors of the article, who also carried out the data analysis presented in supplementary letter 1”. However, the analysis provided by Khromov-Borisov NN was sent to the editor of International Journal of Diabetes Research on Dec 13, 2017 (Supplementary Letter 1). Then editors of Drug Discovery Today (Feb 5, 2018, Supplementary Letter 5), BMJ (Apr 2, 2018), and BMJ EBM assessed the article including analysis mentioned above. Thus Tarasov presented the chronology completely wrong. First we have submitted our criticism of release-activity (RA) to scientific journals and only then Materia Medica sued one of our co-authors.
2. We don’t see how any of our previous criticisms of RA drugs and homeopathy creates a conflict of interest or are relevant to the reception of our article.
3. We have stated that RA drugs contain no active substance. Simple...
Show MoreSergey Tarasov responded to our article “Drug discovery today: no molecules required” with claims of mistakes in our analysis. We are sure that we did not conceal anything of relevance or make any mistakes. This is a response to the claims by Sergey Tarasov.
1. Tarasov claims that one of us has an undeclared conflict of interest: “However, one of the authors of the article, Khromov-Borisov NN, is a defendant in a defamation lawsuit brought by Materia Medica (June 28, 2018). Materia Medica has sued Khromov-Borisov NN <…> this therefore raises serious doubts over the objectivity and impartiality of one of the authors of the article, who also carried out the data analysis presented in supplementary letter 1”. However, the analysis provided by Khromov-Borisov NN was sent to the editor of International Journal of Diabetes Research on Dec 13, 2017 (Supplementary Letter 1). Then editors of Drug Discovery Today (Feb 5, 2018, Supplementary Letter 5), BMJ (Apr 2, 2018), and BMJ EBM assessed the article including analysis mentioned above. Thus Tarasov presented the chronology completely wrong. First we have submitted our criticism of release-activity (RA) to scientific journals and only then Materia Medica sued one of our co-authors.
2. We don’t see how any of our previous criticisms of RA drugs and homeopathy creates a conflict of interest or are relevant to the reception of our article.
3. We have stated that RA drugs contain no active substance. Simple school arithmetic shows that the C12 dilution corresponds to the concentration of initial substance approximately 10^-24 g in 100 ml of the solvent. The mass 10^-24 g is less than the mass of a single proton or neutron (10^-24 g = 0.6 proton).
Nonetheless, Tarasov qualifies such calculations “theoretical assumptions” and states that “the available experimental data refute the authors' theoretical assumptions that in principle ultra-high dilutions cannot contain molecules.” However, the proponents of “release-activity” claim that “high dilutions no longer containing molecules of the original substance are able to cause a physiological reaction based on molecular-level effects.” Epstein O. The Spatial Homeostasis Hypothesis. Symmetry 2018, 10(4), 103. And that “Technologically processed dilutions also exert activity when they do not contain molecules of parent substance”. Epstein O. The phenomenon of release activity and the hypothesis of "spatial" homeostasis. Usp Fiziol Nauk. 2013 Jul-Sep;44(3):54-76
None of the RA articles we mention have provided concentrations of active substances, which is a flaw we discuss in our analysis. The idea that initial substances can somehow survive such dilutions (if true) works against the existence of the phenomena of “release-activity” and makes the discussed RA studies meaningless.
4. In our article we state that “There is no mention that Epstein is the CEO and founder of MMH”. Tarasov claims that “the concealment of a conflict of interest claimed by Panchin AY et al. therefore has no basis in fact.” To that we will repeat one more time: “There is no mention that Epstein is the CEO and founder of MMH”. This is conflict of interest that was not reported. And it’s a fact. We are content that Sergey Tarasov did not disagree with our concerns about concealed conflicts of interest in other RA articles.
5. In our article we state that “The authors failed to provide images of acquired blots, making it impossible to check the validity of their analysis (Supplementary Letter 2)”. Tarasov replied that: “the Editorial Board of Nutrition & Diabetes was provided with images of acquired blots during the peer-reviewing process”. However, we asked for these images both from the Editor of Nutrition & Diabetes (Sep 18, 2018) and from the corresponding author of the article (Nov 11, 2018). The Editor replied (Sep 21, 2018) but did not provide us with any data and suggested we ask for the data from the authors. The authors also did not respond to our e-mail or provide the required data. For some reason Sergey Tarasov, Director of Research & Development Department OOO “NPF “Materia Medica Holding”, also decided not to provide this data in his response. We would be happy to see it.
6. In our article we state that: “The champion in publishing research on RADs is a Russian journal, Bulletin of Experimental Biology and Medicine (English edition is by Springer Nature) <…> Notably, at least 48 of them were published in issue 135 Supplementary 7 (2003) (ref.40). It might be not surprising that Epstein was the editor of this supplementary issue (ref.41)”. Tarasov replies that “this collection is a special edition of the journal supplement” and that “It is not surprising that O.I. Epstein, a scientist who studies this phenomenon, was one of the editors of the special edition”. We don’t see how this is relevant or changes the fact that the editor who published most articles on RA drugs was both a person with a conflict of interest and coauthor of the papers.
7. Tarasov questions how we selected the articles for our analysis. We have addressed articles on RA drugs mentioned in the Drug Discovery Today review (highest impact factor journal which published article by Epstein OI). We did not analyze the article from Bulletin of Experimental Biology and Medicine due to how that journal handled the other RA drug articles (see paragraph above) and its overall low quality. We added the discussion of two more articles because we were already discussing them with the Editors when we discovered the Drug Discovery Today review. We would like to note that our article is not a meta-analysis. However, we hope that it will launch independent investigations of all published articles concerning RA drugs.
8. Tarasov claims that “one of the main reasons why our article was retracted from PLOS ONE [Gavrilova ES, Bobrovnik SA, Sherriff G, et al. Novel approach to activity evaluation for release-active forms of anti-interferon-gamma antibodies based on enzyme-linked immunoassay. PLoS One 2014;9:e97017.] was incomplete conflict of
interest information disclosure“.However, the retraction statement of PLOS ONE (https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197086) also states clearly: “During the journal’s post-publication assessment of this work, concerns were also raised about insufficient methodological reporting in the published article that obfuscate the assessment of the study design. The authors provided additional details about methods and reagents used in response to the journal’s queries, but even in consideration of these the fundamental concerns remain about the premise of the study, the assay used, and the overall reliability of the conclusions”.
We have provided detailed criticism of the methods, results and conclusions in this retracted study and our concerns have not been addressed by the authors (Supplementary Letter 4). Thus, we stand by our conclusion that the article is flawed and agree with the decision of PLOS ONE to retract it.9. Sergei Tarasov states that “In respect to the statistical analysis presented by us in the original article (Journal of Diabetes Research), there are no statistical adjustments for multiple comparisons because the null hypothesis of the study was to compare Subetta with control at certain time point but not in dynamic and to compare effect within the group”.
However, the authors of the discussed paper have reported multiple (27 of 120, excluding the effects of a real drug Rosiglitazone) statistically significant effects which when using adequate and correct statistical procedures appear to be false.
The requirement to adjust the p-values for multiple comparisons is fixed in several most authoritative guidelines and checklists:
“Indicate whether and how any allowance or adjustments were made for multiple comparisons (performing multiple hypothesis tests on the same data).” Lang T.A., Altman D.G. Statistical analyses and methods in the published literature: The SAMPL guidelines. Medical Writing, 2016; 25(3):31 – 36. http://journal.emwa.org/statistics/statistical-analyses-and-methods-in-t...
“Describe adjustments were made for multiple comparisons.” Ghasemi A., Bahadoran Z., Zadeh-Vakili A., Montazeri S.A., Hosseinpanah F. The principles of biomedical scientific writing: materials and methods. Int. J. Endocrinol. Metab. 2019; 17(1):e88155. doi: 10.5812/ijem.88155. https://neoscriber.org/cdn/dl/91aee4ae-2490-11e9-ab2c-3360f3fcc2f4
“Adjustments made for multiple testing is explained.” Nature Statistical Checklist, http://image.sciencenet.cn/olddata/kexue.com.cn/upload/blog/file/2010/12...
“Are there adjustments for multiple comparisons?”
https://media.nature.com/full/nature-assets/ncomms/authors/ncomms_lifesc...“Are statistical inferences corrected for multiple comparisons?” Reporting Checklist for Nature Neuroscience https://authors.library.caltech.edu/47880/13/nn.3767-S2.pdf
Adjustment for the multiplicity testing (multiple comparisons) was used in one of the papers cited by Tarasov:
“The statistical significance of each ELISA and area under the curve (AUC) graph was measured using Mann-Whitney U test (one-tailed) or a one-way ANOVA with Bonferroni’s post hoc test.”Kim, K.-S. et al. The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. Sci. Rep. 5, 18325; doi: 10.1038/srep18325 (2015). https://www.nature.com/articles/srep18325.pdf
Bonferroni’s post hoc test means such an adjustment and is one of the most widely used.
We could respond to Sergei Tarasov about why we used regression analysis, but it does not really matter what analysis we use. The results are the same. For example, we carried out the ANOVA for this data. Details of this analysis with tables and figures can be found here: https://tinyurl.com/y9kbtclr. This ANOVA analysis was done by Khromov-Borisov NN.
The conclusion stands: three “release-active” preparations (AIR, AeNOS and its composition, Subetta) have no antidiabetic effects in the diabetic Goto-Kakizaki rat.
Show LessConflict of Interest:
None declared. - Published on: 25 December 2018Defamation: no evidence required
- Sergey Tarasov, Director of Research & Development Department OOO “NPF “Materia Medica Holding”
The article “Drug discovery today: no molecules required” (2018) (by Panchin AY, Khromov-Borisov NN, Dueva EV) questions the imperfections in reviewing scientific publications. The authors use the example of publications on released-active drugs (RA-drugs) as a basis for the paper and their accusations against journal editorial boards. The authors postulate that these drugs do not contain any active ingredients due to the technology used and therefore come to the conclusion that the reviewers and journal editors who have published articles on RA-drugs carried out their work appallingly and made gross mistakes. So the authors state «…the vast amount of flawed publication claiming therapeutic properties and physiological effects of drugs with no active components can highlight the problems of peer-review standards and policies in biomedical journals».
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This particular conclusion is based on approximate theoretical calculations and not on experimental evidence: «If one assumes a 1M initial antibodies concentration (though this is usually not disclosed in release-activity papers) and takes into account Avogadro’s constant (~6.02×10^23 mol^(−1)), then even C12 dilutions are unlikely to contain any antibody molecules». In their article, the authors present these calculations as the main argument to complain to journals. It is noteworthy that in the article the authors do not provide any data or references to any studies conducted by themselves. Neither do the authors provid...The article “Drug discovery today: no molecules required” (2018) (by Panchin AY, Khromov-Borisov NN, Dueva EV) questions the imperfections in reviewing scientific publications. The authors use the example of publications on released-active drugs (RA-drugs) as a basis for the paper and their accusations against journal editorial boards. The authors postulate that these drugs do not contain any active ingredients due to the technology used and therefore come to the conclusion that the reviewers and journal editors who have published articles on RA-drugs carried out their work appallingly and made gross mistakes. So the authors state «…the vast amount of flawed publication claiming therapeutic properties and physiological effects of drugs with no active components can highlight the problems of peer-review standards and policies in biomedical journals».
This particular conclusion is based on approximate theoretical calculations and not on experimental evidence: «If one assumes a 1M initial antibodies concentration (though this is usually not disclosed in release-activity papers) and takes into account Avogadro’s constant (~6.02×10^23 mol^(−1)), then even C12 dilutions are unlikely to contain any antibody molecules». In their article, the authors present these calculations as the main argument to complain to journals. It is noteworthy that in the article the authors do not provide any data or references to any studies conducted by themselves. Neither do the authors provide references to outside studies. Hence, the question arises as to whether theoretical calculations may be sufficient to support the accusations made by the authors. In this regard, the available experimental data refute the authors' theoretical assumptions that in principle ultra-high dilutions cannot contain molecules. So, Chikramane PS et al. (2012) wrote in the pages of American Chemical Society journal ‘Langmuir’: «However, physicochemical studies of these solutions have unequivocally established the presence of the starting raw materials in nanoparticulate form even in these extreme (super-Avogadro, >10^23) dilutions. In this paper, we propose and validate a hypothesis to explain how nanoparticles are retained even at such enormous dilution levels» [Chikramane PS, Kalita D, Suresh AK, Kane SG, Bellare JR. Why extreme dilutions reach non-zero asymptotes: a nanoparticulate hypothesis based on froth flotation. Langmuir. 2012; 28(45):15864-75. doi: 10.1021/la303477s]. Consequently, the main thesis on which the authors base their criticism is rendered invalid at least because the subject is complicated and should not be simplified as Panchin AY et al did.The article itself contains a number of errors. I shall provide some examples:
In Table 1, in the paragraph about the article in Nutrition & Diabetes it is stated: “There is no mention that Epstein is the CEO and founder of MMH”. This is presented as if a conflict of interest is being withheld. However, the article's “Conflict of interest” section (Nutrition & Diabetes) in fact discloses information about the employment of all the co-authors of the article: “This work was funded by (OOO ‘NPF ‘MATERIA MEDICA HOLDING’, Russian Federation). EAG, SAT, EVK and OIE have an affiliation to the commercial funders of this research study (OOO ‘NPF ‘MATERIA MEDICA HOLDING’, Russian Federation) and JN is employed by a commercial company (Zen-Bio Inc., USA).” (NOTE: OIE – Oleg I Epstein). The concealment of a conflict of interest claimed by Panchin AY et al. therefore has no basis in fact.
Furthermore, in Table 1, the paragraph concerning the same article in Nutrition & Diabetes states the following: “The authors failed to provide images of acquired blots, making it impossible to check the validity of their analysis (online supplementary letter 2)”. Actually, the Editorial Board of Nutrition & Diabetes was provided with images of acquired blots during the peer-reviewing process. However, due to the format of the article (Short Communications) and limitations in the number of figures and tables, which could be displayed in the article, the images of blots just did not get into the published article. Thus, Panchin AY et al. statement is absolutely wrong.
As for the repeated statistical analysis based on the article in the Journal of Diabetes Research (Table 1 and online supplementary letter 1) conducted by the authors, I report that this analysis contains enough errors to consider it inadequate. Regression analysis used in supplementary letter 1 makes several assumptions. There must be a linear relationship between day and plasma glucose level, residuals should be normally distributed (this information cannot be accessed from the tables in the article), independent variables are not highly correlated with each other and the variance of errors should be similar across all independent variables. Violation of these assumptions makes use of regression analysis inappropriate. Thus, the results in supplementary letter 1 are not reliable and cannot serve as evidence of the absence of significant differences. In respect to the statistical analysis presented by us in the original article (Journal of Diabetes Research), there are no statistical adjustments for multiple comparisons because the null hypothesis of the study was to compare Subetta with control at certain time point but not in dynamic and to compare effect within the group. That is why Mann-Whitney test was done for the inter group comparison and Wilcoxon test was done for the comparison with respective control. The application of the similar approach could be easily found in articles of other research groups [for instance, Shimoda M. et al. Diabetologia. 2011;54(5):1098-108; Ropero A.B. et al. PLoS One. 2012;7(4):e34650; Gruzman A. et al. J Cell Mol Med. 2012;16(3):594-604; Chen C. et al. Dis Model Mech. 2014;7(6):723-30; Kim K.S. et al. Sci Rep. 2015;5:18325]. In this case FDR adjustment and regression analysis used in supplementary letter 1 to evaluate research results are not only inappropriate but also uninformative and meaningless.
Also, there are inaccuracy in the article as well. The article states “The champion in publishing research on RADs is a Russian journal, Bulletin of Experimental Biology and Medicine (English edition is by Springer Nature)… Notably, at least 48 of them were published in issue 135 Supplementary 7 (2003) (ref.40). It might be not surprising that Epstein was the editor of this supplementary issue (ref.41)”. In the process, the authors fail to mention that it was a collection of works on studying drugs based on ultra-low doses, as indicated in the Russian edition (http://www.iramn.ru/journal/bebm/2003/bbm031p.htm; in Russian). In other words, this collection is a special edition of the journal supplement. It is not surprising that O.I. Epstein, a scientist who studies this phenomenon, was one of the editors of the special edition. This detail is critical to understanding why so many works by one author were published in the journal. However, this detail was simply swept under the carpet by Panchin AY et al.
Let me consider another example of how information is presented in a favourable light for the authors. The article states “Drug Discovery Today—one of the leading journals in the field—published a review coauthored by Epstein about the structure and dynamics of the IR16 that claims the miraculous physiological activity for the RAD subetta…”. This review is devoted to the structure and dynamics of the insulin receptor rather than the study of Subetta. This drug is listed among other drugs that target the insulin receptor and the associated signalling pathway. Therefore, the review in Drug Discovery Today does not in any way claim to be “miraculous physiological activity for the RAD Subetta”, as the authors put it.
Finally, the article does not stipulate how the six articles (presented in Table 1) were chosen for analysis. Any data analysis must be based on clear criteria according to which material is included and excluded. Otherwise, materials may be selected in order to confirm the author's point of view. As the authors themselves write, over 100 English-language articles have been published about RA-drugs. Among the publications there are many articles about the results of clinical studies of RA-drugs, including those in specialised English-language scientifically peer-reviewed journals. It should be noted that it is only the results of clinical studies that allow discussion of a particular drug's efficacy. The authors did not include an analysis of such articles into their «analysis». However, sweeping conclusions were made about RA-drugs' lack of efficacy based on the analysis of six non-clinical articles, of which:
1. one is devoted to the development of the ELISA method, and not to the evaluation of RA-drugs’ pharmacological activity;
2. one is a review of the structure of an insulin receptor, rather than an evaluation of pharmacological activity of RA-drugs;
3. two articles are in vitro studies of a possible mechanism of action, and yet again not an assessment of efficacy of RA-drugs;
4. and only two articles are devoted to the evaluation of pharmacological activity of RA- drugs.
Thus, the generalisations that the article's authors make based on their selective analysis cast doubt on their validity and impartiality.The authors of this publication, whilst reproaching the co-authors of articles concerning RA-drugs for concealing a conflict of interest, in fact violate conflicts of interests themselves. This is impermissible in principle, as authors who have taken it upon themselves to judge other articles must fully comply with the rules of the journal, otherwise the publication resembles a caricature. The authors stated in the article: “Competing interests: None declared”.
In accordance with “ICMJE Form for Disclosure of Potential Conflicts of Interest” that all authors must complete (http://www.icmje.org/coi_disclosure.pdf), they must indicate if there are “relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work”.
In accordance with ICMJE uniform declaration of competing interests, authors should disclose (https://authors.bmj.com/policies/competing-interests/) “Non-financial associations that may be relevant to the submitted manuscript”.
However, one of the authors of the article, Khromov-Borisov NN, is a defendant in a defamation lawsuit brought by Materia Medica (June 28, 2018). Materia Medica has sued Khromov-Borisov NN, one of the article co-authors, for harming business reputation after he published inaccurate and discrediting information about the Company’s activities in the mass media (newspaper article in Troitsky Variant – Science; it is ‘journalistic’ but not scientific article) (А40-148616/2018) (http://kad.arbitr.ru/Card/a74a5f06-fff8-4b4a-b5c0-3f97c33d36c1; in Russian). This therefore raises serious doubts over the objectivity and impartiality of one of the authors of the article, who also carried out the data analysis presented in supplementary letter 1. So, here might be a personal dislike and personal interest in discrediting Materia Medica and its scientific activities.
In addition, according to the BMJ policy (https://authors.bmj.com/policies/competing-interests/): “Examples of competing interests include the following: … other personal or professional relationships that may influence or appear to influence”.
The authors concealed that Panchin AY and Khromov-Borisov NN are members of the Commission of the Russian Academy of Sciences on Pseudoscience and Research Fraud (http://klnran.ru/about/sostav/; in Russian) (hereinafter “The Commission”). This membership may influence or appear to influence on the content of the article taking into account that the Commission published “Memorandum No.2. Homeopathy as Pseudoscience” (2017) (hereinafter “Memorandum”) in which not only homeopathy, but also RA-drugs was criticised.
The information worth mentioning for clear understanding the status of the Commission and the Memorandum: after its release, Prosecutor's check revealed that the Memorandum is not an official position of Russian Academy of Sciences (RAS), but is a personal scientific opinion of the Memorandum's authors. Moreover, in the court case №А40-217689/2017 (http://kad.arbitr.ru/Card/c1c31039-1951-432c-9625-99a6ef871676; in Russian) regarding the Memorandum it was proved that:
1. the Commission is not a structural unit of RAS;
2. the Commission shall conduct any researches under an order of the Presidium of the RAS that did not give the order for the preparation of the Memorandum;
3. the experts' opinion, which serves as basis for the Memorandum, was signed by the Head of this Commission and by 7 members of the Commission (including Panchin AY; the full number of its members is 63);
4. all persons, who signed the Memorandum, are not employed by RAS.Incidentally, Panchin AY is a member of the board of the Evolution Fund (https://evolutionfund.ru/about#council; in Russian), which supported the preparation of the Memorandum (http://klnran.ru/2017/02/memorandum02-homeopathy/; in Russian). The fund provides support for publishing Panchin's books (https://evolutionfund.ru/project/1; in Russian), some containing negative information regarding Materia Medica’s drugs (Panchin A. Zashchita ot temnykh iskusstv. Putevoditel' po miru paranormal'nykh yavleniy / A. Panchin — «Corpus (AST)», 2018 — 396p. (ISBN: 978-5-17-982690-3) [Library of the Evolution Fund]). Several members of the board of the Evolution Fund (https://evolutionfund.ru/about#council; in Russian) are the members of Editorial Board of the newspaper Troitsky Variant – Science (https://trv-science.ru/about/editors/; in Russian). This newspaper, as well as Khromov-Borisov NN, is a defendant in a defamation lawsuit brought by Materia Medica (June 28, 2018) (see above). Thus, the above-mentioned information should be disclosed in accordance with “ICMJE Form for Disclosure of Potential Conflicts of Interest” which indicates the requirement to disclose “Relevant financial activities outside the submitted work”: “This section asks about your financial relationships with entities in the bio-medical arena that could be perceived to influence, or that give the appearance of potentially influencing, what you wrote in the submitted work. You should disclose interactions with ANY entity that could be considered broadly relevant to the work. For example, if your article is about testing an epidermal growth factor receptor (EGFR) antagonist in lung cancer, you should report all associations with entities pursuing diagnostic or therapeutic strategies in cancer in general, not just in the area of EGFR or lung cancer”.
I would like to call attention to the fact that one of the main reason why our article was retracted from PLOS ONE [Gavrilova ES, Bobrovnik SA, Sherriff G, et al. Novel approach to activity evaluation for release-active forms of anti-interferon-gamma antibodies based on enzyme-linked immunoassay. PLoS One 2014;9:e97017.] was incomplete conflict of interest information disclosure. Moreover, I would like to remind that the affiliations of all authors were stated in the article, and the fact that the drug used for the method development is the commercial product of the pharmaceutical company is mentioned in the “Materials and Methods” section. During the review process neither the editors, nor the reviewers suggest that this information should also be mentioned in the “Conflict of interest” section. Thus, information about the authors' employment and the presence of a commercially available drug sold by the company was, in fact, provided in the article, albeit not in a separate section. At the same time, no information is presented in the Panchin AY et al. article concerning possible conflict of interests, which would allow Editor board, reviewers and readers to formulate their own position with regard to the published material and its authors.
Concluding remarks.
Thus, the article “Drug discovery today: no molecules required” (2018) (by Panchin AY, Khromov-Borisov NN, Dueva EV) is devoted to the imperfection of reviewing scientific publications. The authors use the example of publications on RA-drugs as the basis for their conclusions and accusations against the editorial boards of various journals theoretically postulating that the drugs do not contain active ingredients, making mistakes and inaccuracies in the presentation of materials, concealing a potential conflict of interest and other information that may be useful for readers to evaluate this article.Additional information.
I do not give a detailed description of work dedicated to RA-drugs, as the main topic of the article is different. This is also due to the fact that Panchin AY et al. promote them rather successfully, not only in the scientific domain but also in the non-scientific. The article fleetingly mentions the scale of the research, which includes the entire range of works from research at the early stages of drug development to clinical trials. It reflects a systematic approach to research and development, as well as potentially supporting the conclusions of the RA-drug developers on their efficacy. It is only possible to comment on and add to some of the points:
1. Availability of RA-drugs both in Russia and abroad would be impossible without the proper evaluation of quality, efficacy and safety of the drugs carried out by Ministries of health of these countries followed by authorizing the drugs on the basis of the evaluation conducted. It is well known that evaluation of a drug is based on the main principles: legality, independence of an evaluator, objectivity, comprehensiveness and completeness of research carried out using modern science and technology. The plans to expand drug’s presence in Europe and the US are based on scientific consultations with experts from the FDA, MHRA, and EMA, as well as their positive conclusions based on the analysis of data provided by the company about the drugs.
2. Information and results of clinical trials are published openly on the specialist website clinicaltrials.gov, which is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH). Publishing data on this resource is not mandatory, and therefore indicates the transparency of the drug developer's policy with regard to the findings. Processing the results takes time, so it is not surprising that out of 13 completed studies conducted in accordance with all the principles of Good Clinical Practice (GCP), results have only been presented for five so far. Unsurprisingly, the drug developer ranks first among Russian pharmaceutical companies in terms of the number of clinical trials in Russia, as of the third quarter of 2018. [SYNERGY RESEARCH GROUP, Research Report. Clinical trials in Russia. Autumn 2018; https://synergycro.ru/orange_paper/Synergy_Orange_Paper_Russia_2018Q3.pdf].
3. The drug’s market position in Russia reflects demand for the products, which the numerous awards received by the company demonstrate.
4. The authors mention more than 100 English-language articles published as a result of the drugs research. These publications are based on the results of many experiments (including efficacy, safety, mechanism of action, specificity, dose-dependence, etc.) conducted by independent research teams at various experimental sites (universities, institutes and laboratories) in dozens of countries around the world. Clinical studies have been conducted with the participation of hundreds of clinical sites.Finally, it should be mentioned that the majority of articles dedicated to RA-drugs was published many years ago. Until recently not a single reader has written any concern to the journals regarding them. Now there is a group of authors who aim at this subject. The articles criticized by Panchin AY et al. were published in 2013-2017 but the requests to the journals were sent 1-3 years later. So the question of sincerity and impartiality of those who publicly lead the work aimed at discrediting RA-drugs arises.
Show LessConflict of Interest:
Tarasov SA is employee of OOO “NPF “Materia Medica Holding”, the company, which produces and markets RA-drugs. Tarasov SA is co-author in the papers dedicated to the RA-drugs described in the article by Panchin et al. (2018) BMJ Evidence-Based Medicine. doi: 10.1136/bmjebm-2018-111121. Tarasov SA is co-author of several patents dedicated to RA-drugs. OOO “NPF “Materia Medica Holding” has sued Khromov-Borisov NN (А40-148616/2018) (http://kad.arbitr.ru/Card/a74a5f06-fff8-4b4a-b5c0-3f97c33d36c1; in Russian).