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Reporting Experiments in Homeopathic Basic Research (REHBaR)
Homeopathy (2015) -, 1e4 Ó 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.homp.2015.06.006, available online at http://www.sciencedirect.com
Reporting Experiments in Homeopathic Basic Research (REHBaR) Beate Stock-Schr€ oer Karl and Veronica Carstens e Foundation, Essen, Germany Introduction: The aim of this study was to develop a criteria catalogue serving as a guideline for authors to improve quality of Reporting Experiments in Homeopathic Basic Research (REHBaR). Main focus was in the field of biochemical and biological experiments. So far, there was no guideline for scientists and authors available, unlike criteria catalogues common in clinical research. Methods: A Delphi Process was conducted among experts who published experimental work within the last five years in this field. The process included a total of five rounds, three rounds of adjusting and phrasing plus two consensus conferences. Results: A checklist of 23 items was achieved, augmented with detailed examples how to handle each item while compiling a publication. Background, objectives and possible hypotheses are necessary to be given in the part ‘introduction’. The section ‘materials and methods’ is the most important part, where a detailed description of chosen controls, object of investigation, experimental setup, replication, parameters, intervention, allocation, blinding, and statistical methods is mandatory. In the ‘results’ section sufficient details on analysed data, descriptive as well as inferential are needed. Moreover, authors should discuss their results and interpret them in the context of current evidence. REHBaR was compiled for authors when preparing their manuscripts, and to be used by scientific journals in the reviewing process. Conclusions: Reporting experiments in basic research in homeopathy is an important issue to state the quality and validity of gained results. A guideline for REHBaR seemed to be the first step to come to a commitment what information is necessary to be given in a paper. More than that, the catalogue can serve as a statement what the standards in good basic research should be. Homeopathy (2015) -, 1e4.
Key words: Reporting; Checklist; Quality; Experiments; Ultra high dilution; Homeopathy
Introduction Homeopathy is a highly controversial discussed subject due to the fact that in clinical research a proof of specific effects of homeopathy in general and of high potencies in particular is still lacking. Laboratory research is in the focus of interest to investigate whether homeopathic preparations have biological activity at all and which mechanism of action is the possible underlying principle. Any publication reporting research on homeopathy, particularly if reporting positive results, attracts attention and is carefully considered regarding the quality of the study.
E-mail: [email protected] Received 20 May 2015; accepted 12 June 2015
As there are many experiments differing in design and quality1 several efforts have been made to enhance the quality of basic research in homeopathy over the years. In UHD 1994, Schulte elaborated a number of standards for ultra high dilution research,2 Linde et al. proposed checklists for preparing and reviewing publications3 and Baumgartner et al. discussed methodological standards4 already. Moreover there were two papers to establish scoring systems for assessing the quality of publications: The first applicable in experimental toxicology5 the second for physicochemical research.6 The latter score was adapted for the use in a systematic review on in vitro experiments.1 In the first place, a team of experienced researchers in this field came together to develop a new evaluation score applicable in all fields of basic research on homeopathy based on existing evaluation scores. Discussing the
Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting basic research B Stock-Schro€er
2
Figure 1 Flow chart of the Delphi Process from October 2007 to March 2009 among a panel of European scientists on homeopathy for developing the checklist REHBaR.
preparatory work during the consensus conference, we came to the result that before developing a score system a previous step is necessary: the development of a checklist for authors, peer reviewers and editors similar to several publication guidelines in clinical research (CONSORT, REDHOT, e.g.). Reporting experiments in basic research concerned with homeopathic substances requires a complete and detailed
explanation of what exactly the trial was about, which materials were used and how it was conducted and assessed. Authors should provide all information to enable readers to understand and scientists to replicate their experiments. The aim of this investigation was to develop a criteria catalogue as a guideline for authors how to write a paper and how to include all indispensable information into a publication.
Homeopathy Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting basic research B Stock-Schro€er
3
Methods We have chosen a Delphi Process which is a widely used consensus method to structure a group communication process.7 Members of the panel were, among others, K. Linde and C. Witt who worked and published on questions of guidelines and quality in basic research or clinical research within the last 10 years.5,6 S. Baumgartner, L. Betti, C. Endler and R. van Wijk participated as leading European researchers in homeopathic experiments with plants, animals, evolutionary biology as well as biochemical and biophysical research. More information about the members is given in another publication.8 The Delphi Process is characterized as a structured method within a group of persons dealing with a complex research or therapy question. It undergoes a number of steps of adjusting and wording to achieve a compromise course of action. In the case of issue a consented checklist was developed with criteria important for improving the quality of reports in basic research in homeopathy. We initiated a Delphi Process including a total of five rounds, three rounds of adjusting and phrasing plus two consensus conferences. An overview of the process is given in
Figure 1, a detailed description of the Delphi Process (preparatory phase, Delphi IeIV) is given elsewhere.8 An elaboration of all items and their explanation together with a prime example for each item was selected in round V and published in detail9 and can be downloaded among other guidelines here: http://www.equator-network. org/reporting-guidelines/reporting-experiments-inhomeopathic-basic-research-rehbar-a-detailed-guidelinefor-authors.
Results The aim of the Delphi Process within a group of experts was to compile a catalogue of criteria indispensable for writing a publication in this field of research. The final catalogue of 23 criteria as the result of Delphi IV in form of a checklist is given in Table 1. In the last round (V) of the Delphi Process, as discussed in the 2nd consensus conference, we decided that such a catalogue is only applicable for authors when each item is explained comprehensively and illustrated by giving an appropriate example, collected from different publications. This detailed explanation of how these criteria can be used
Table 1 Items to be included when Reporting Experiments in Homeopathic Basic Research Item
No
Description
Title Abstract Introduction Background
1 2
Title indicates the experimental model and the intervention Abstract provides an informative and balanced summary of what was done and found
3
Objectives/Hypotheses
4
Scientific background, presentation of experimental model(s), explanation of rationale, including homeopathic principles (e.g. similiar principle, potentisation, proving) and type of homeopathy (isopathy, classical vs complex homeopathy) Objectives and hypotheses with outcome measures. For confirmatory experiments: specific hypotheses and clearly defined primary outcome measure. For exploratory experiments: hypotheses inducing the investigations.
Materials and methods Materials Materials (homeopathy specific)
5 6
Homeopathic controls System performance controls Quality control Object of investigation Experimental setup Replication
7 8 9 10 11 12
Parameters Intervention
13 14
Allocation
15
Blinding Statistical methods
16 17
Results Numbers analysed
18
Data (descriptive)
19
Data (inferential) Discussion Interpretation
20 21
Evidence
22
Experimental model
23
Detailed description of all used materials (e.g. biological system, devices, substances, instruments) Manufacturer, Pharmacopoeia (or process) of medications, potency and steps of dilution, dilution method, substance starting point of dilution (e.g. mother tincture, D1, nosode) Precise details on the preparation of the control substance Report on negative and positive controls Procedures and efforts used to enhance the quality and reliability of the experimental procedure Selection criteria for the particular system used: in vivo, in vitro, biological, physical, biochemical Detailed description of experimental conditions and procedure If experiment has internal replications, detailed description is given of which materials were reused and which have been changed All measured parameters described in detail Precise details of the interventions intended for each group and how and when they were actually administered Method used to generate the group allocation including details (e.g. randomisation, blocking, stratification) Description if any procedures or interventions were concealed (if yes, details given) Statistical tests and procedure of calculation are described: Methods for additional analyses like adjusted analyses Number of experiments with exact number of treated units per setting which were included in each analysis and reporting missing samples, drop outs Results are given in tables or figures showing mean or median together with variability (e.g. SD and/or range) for absolute data (and differences) Gives appropriate measures of effect size, uncertainty and probability Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision General interpretation of results in the context of current evidence. Discuss the generalisability/ external validity of the study results Explanation why this model, these parameters were chosen and its adequacy for answering the questions including homeopathic aspects
Homeopathy Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting basic research B Stock-Schro€er
4
for preparing a publication of a high quality is given elsewhere.9 We recommend explicitly to refer to these explanations while using the criteria catalogue.
Discussion A Delphi Process was initiated in order to achieve a concerted criteria catalogue of what is important to describe in a publication concerned with basic research in homeopathy. A group of experts were asked to participate in this consensus process and contribute their aspects of indispensable research issues connected with publications of high quality and transparency. A publication is the only source of information for readers to gain a comprehensive insight into what the investigation is about, which methods were used and how results were obtained. The criteria catalogue Reporting Experiments in Homoepathic Basic Research (REHBaR) was developed among a group of scientists in a Delphi Process to improve the quality of reporting experiments in this research area. Space limitations given by journals can make work hard to report properly. We recommend to subdivide reports on research into different publications, so that at least one publication can focus on the methodological part in detail and proceeding papers can refer to those preliminary descriptions. The aim of this investigation was to develop a criteria catalogue as a guideline for authors and it was not intended thus far to give instructions how to conduct good basic research on homeopathy. Although, by discussing items researchers need to know about experiments to assess the quality of the paper, we came to the conclusion that in fact this list can count also as an orientation of what good laboratory practice in this field means. Another group of experts might have contributed further or other aspects. Therefore, we encouraged readers of our
publications in 2009 to comment our work and give a feedback on how feasible the list is. We tried to consider all aspects of the four main areas of basic research on homeopathy, as there are animal research, plant bioassays, in vitro models and physicochemical research, so that this catalogue should be feasible to all fields of research for authors writing their publications.
References 1 Witt C, Bluth M, Albrecht HT, Weißhuhn T, Baumgartner S, Willich S. The in vitro evidence for an effect of high homeopathic potencies e a systematic review of the literature. Complementary Ther Med 2007; 15(2): 128e138. 2 Schulte J. About quality and standards in ultra high dilution research and research on homeopathy. In: Endler PCSJ (ed). Ultra High DilutiondPhysiology and Physics. Dordrecht, The Netherlands: Kluwer Academic Publishers, 1994, pp 171e176. 3 Linde W, Melchart D, Jonas W, Hornung J. Ways to enhance the quality and acceptance of clinical and laboratory studies in homoeopathy. Br Homoeopath J 1994; 83(1): 3e7. 4 Baumgartner S, Heusser P, Thurneysen A. Methodological standards and problems in preclinical homoeopathic potency research. Forsch Komplementarmedizin Klass Naturheilkd 1998; 5(1): 27e32. 5 Linde K, Jonas W, Melchart D, Worku F, Wagner H, Eitel F. Critical review and meta-analysis of serial agitated dilutions in experimental toxicology. Hum Exp Toxicol 1994; 13(7): 481e492. 6 Becker-Witt C, Weißhuhn T, L€ udtke R, Willich S. Quality assessment of physical research in homeopathy. J Altern Complementary Med 2003; 9(1): 113e132. 7 Linstone H, Turoff M. The Delphi method: techniques and applications, http://www.is.njit.edu/pubs/delphibook/; 2002. 8 Stock-Schr€ oer B, Albrecht H, Betti L, et al. Reporting experiments in homeopathic basic research (REHBaR) e description of the checklist development. eCAM 2009; http://dx.doi.org/10.1093/ecam/nep170. 9 Stock-Schr€ oer B, Albrecht H, Betti L, et al. Reporting Experiments in Homeopathic Basic Research (REHBaR) e a guideline for authors. Homeopathy 2009; 98: 287e298.
Homeopathy Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting Experiments in Homeopathic Basic Research (REHBaR) Beate Stock-Schr€ oer Karl and Veronica Carstens e Foundation, Essen, Germany Introduction: The aim of this study was to develop a criteria catalogue serving as a guideline for authors to improve quality of Reporting Experiments in Homeopathic Basic Research (REHBaR). Main focus was in the field of biochemical and biological experiments. So far, there was no guideline for scientists and authors available, unlike criteria catalogues common in clinical research. Methods: A Delphi Process was conducted among experts who published experimental work within the last five years in this field. The process included a total of five rounds, three rounds of adjusting and phrasing plus two consensus conferences. Results: A checklist of 23 items was achieved, augmented with detailed examples how to handle each item while compiling a publication. Background, objectives and possible hypotheses are necessary to be given in the part ‘introduction’. The section ‘materials and methods’ is the most important part, where a detailed description of chosen controls, object of investigation, experimental setup, replication, parameters, intervention, allocation, blinding, and statistical methods is mandatory. In the ‘results’ section sufficient details on analysed data, descriptive as well as inferential are needed. Moreover, authors should discuss their results and interpret them in the context of current evidence. REHBaR was compiled for authors when preparing their manuscripts, and to be used by scientific journals in the reviewing process. Conclusions: Reporting experiments in basic research in homeopathy is an important issue to state the quality and validity of gained results. A guideline for REHBaR seemed to be the first step to come to a commitment what information is necessary to be given in a paper. More than that, the catalogue can serve as a statement what the standards in good basic research should be. Homeopathy (2015) -, 1e4.
Key words: Reporting; Checklist; Quality; Experiments; Ultra high dilution; Homeopathy
Introduction Homeopathy is a highly controversial discussed subject due to the fact that in clinical research a proof of specific effects of homeopathy in general and of high potencies in particular is still lacking. Laboratory research is in the focus of interest to investigate whether homeopathic preparations have biological activity at all and which mechanism of action is the possible underlying principle. Any publication reporting research on homeopathy, particularly if reporting positive results, attracts attention and is carefully considered regarding the quality of the study.
E-mail: [email protected] Received 20 May 2015; accepted 12 June 2015
As there are many experiments differing in design and quality1 several efforts have been made to enhance the quality of basic research in homeopathy over the years. In UHD 1994, Schulte elaborated a number of standards for ultra high dilution research,2 Linde et al. proposed checklists for preparing and reviewing publications3 and Baumgartner et al. discussed methodological standards4 already. Moreover there were two papers to establish scoring systems for assessing the quality of publications: The first applicable in experimental toxicology5 the second for physicochemical research.6 The latter score was adapted for the use in a systematic review on in vitro experiments.1 In the first place, a team of experienced researchers in this field came together to develop a new evaluation score applicable in all fields of basic research on homeopathy based on existing evaluation scores. Discussing the
Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting basic research B Stock-Schro€er
2
Figure 1 Flow chart of the Delphi Process from October 2007 to March 2009 among a panel of European scientists on homeopathy for developing the checklist REHBaR.
preparatory work during the consensus conference, we came to the result that before developing a score system a previous step is necessary: the development of a checklist for authors, peer reviewers and editors similar to several publication guidelines in clinical research (CONSORT, REDHOT, e.g.). Reporting experiments in basic research concerned with homeopathic substances requires a complete and detailed
explanation of what exactly the trial was about, which materials were used and how it was conducted and assessed. Authors should provide all information to enable readers to understand and scientists to replicate their experiments. The aim of this investigation was to develop a criteria catalogue as a guideline for authors how to write a paper and how to include all indispensable information into a publication.
Homeopathy Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting basic research B Stock-Schro€er
3
Methods We have chosen a Delphi Process which is a widely used consensus method to structure a group communication process.7 Members of the panel were, among others, K. Linde and C. Witt who worked and published on questions of guidelines and quality in basic research or clinical research within the last 10 years.5,6 S. Baumgartner, L. Betti, C. Endler and R. van Wijk participated as leading European researchers in homeopathic experiments with plants, animals, evolutionary biology as well as biochemical and biophysical research. More information about the members is given in another publication.8 The Delphi Process is characterized as a structured method within a group of persons dealing with a complex research or therapy question. It undergoes a number of steps of adjusting and wording to achieve a compromise course of action. In the case of issue a consented checklist was developed with criteria important for improving the quality of reports in basic research in homeopathy. We initiated a Delphi Process including a total of five rounds, three rounds of adjusting and phrasing plus two consensus conferences. An overview of the process is given in
Figure 1, a detailed description of the Delphi Process (preparatory phase, Delphi IeIV) is given elsewhere.8 An elaboration of all items and their explanation together with a prime example for each item was selected in round V and published in detail9 and can be downloaded among other guidelines here: http://www.equator-network. org/reporting-guidelines/reporting-experiments-inhomeopathic-basic-research-rehbar-a-detailed-guidelinefor-authors.
Results The aim of the Delphi Process within a group of experts was to compile a catalogue of criteria indispensable for writing a publication in this field of research. The final catalogue of 23 criteria as the result of Delphi IV in form of a checklist is given in Table 1. In the last round (V) of the Delphi Process, as discussed in the 2nd consensus conference, we decided that such a catalogue is only applicable for authors when each item is explained comprehensively and illustrated by giving an appropriate example, collected from different publications. This detailed explanation of how these criteria can be used
Table 1 Items to be included when Reporting Experiments in Homeopathic Basic Research Item
No
Description
Title Abstract Introduction Background
1 2
Title indicates the experimental model and the intervention Abstract provides an informative and balanced summary of what was done and found
3
Objectives/Hypotheses
4
Scientific background, presentation of experimental model(s), explanation of rationale, including homeopathic principles (e.g. similiar principle, potentisation, proving) and type of homeopathy (isopathy, classical vs complex homeopathy) Objectives and hypotheses with outcome measures. For confirmatory experiments: specific hypotheses and clearly defined primary outcome measure. For exploratory experiments: hypotheses inducing the investigations.
Materials and methods Materials Materials (homeopathy specific)
5 6
Homeopathic controls System performance controls Quality control Object of investigation Experimental setup Replication
7 8 9 10 11 12
Parameters Intervention
13 14
Allocation
15
Blinding Statistical methods
16 17
Results Numbers analysed
18
Data (descriptive)
19
Data (inferential) Discussion Interpretation
20 21
Evidence
22
Experimental model
23
Detailed description of all used materials (e.g. biological system, devices, substances, instruments) Manufacturer, Pharmacopoeia (or process) of medications, potency and steps of dilution, dilution method, substance starting point of dilution (e.g. mother tincture, D1, nosode) Precise details on the preparation of the control substance Report on negative and positive controls Procedures and efforts used to enhance the quality and reliability of the experimental procedure Selection criteria for the particular system used: in vivo, in vitro, biological, physical, biochemical Detailed description of experimental conditions and procedure If experiment has internal replications, detailed description is given of which materials were reused and which have been changed All measured parameters described in detail Precise details of the interventions intended for each group and how and when they were actually administered Method used to generate the group allocation including details (e.g. randomisation, blocking, stratification) Description if any procedures or interventions were concealed (if yes, details given) Statistical tests and procedure of calculation are described: Methods for additional analyses like adjusted analyses Number of experiments with exact number of treated units per setting which were included in each analysis and reporting missing samples, drop outs Results are given in tables or figures showing mean or median together with variability (e.g. SD and/or range) for absolute data (and differences) Gives appropriate measures of effect size, uncertainty and probability Interpretation of the results, taking into account study hypotheses, sources of potential bias or imprecision General interpretation of results in the context of current evidence. Discuss the generalisability/ external validity of the study results Explanation why this model, these parameters were chosen and its adequacy for answering the questions including homeopathic aspects
Homeopathy Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006
Reporting basic research B Stock-Schro€er
4
for preparing a publication of a high quality is given elsewhere.9 We recommend explicitly to refer to these explanations while using the criteria catalogue.
Discussion A Delphi Process was initiated in order to achieve a concerted criteria catalogue of what is important to describe in a publication concerned with basic research in homeopathy. A group of experts were asked to participate in this consensus process and contribute their aspects of indispensable research issues connected with publications of high quality and transparency. A publication is the only source of information for readers to gain a comprehensive insight into what the investigation is about, which methods were used and how results were obtained. The criteria catalogue Reporting Experiments in Homoepathic Basic Research (REHBaR) was developed among a group of scientists in a Delphi Process to improve the quality of reporting experiments in this research area. Space limitations given by journals can make work hard to report properly. We recommend to subdivide reports on research into different publications, so that at least one publication can focus on the methodological part in detail and proceeding papers can refer to those preliminary descriptions. The aim of this investigation was to develop a criteria catalogue as a guideline for authors and it was not intended thus far to give instructions how to conduct good basic research on homeopathy. Although, by discussing items researchers need to know about experiments to assess the quality of the paper, we came to the conclusion that in fact this list can count also as an orientation of what good laboratory practice in this field means. Another group of experts might have contributed further or other aspects. Therefore, we encouraged readers of our
publications in 2009 to comment our work and give a feedback on how feasible the list is. We tried to consider all aspects of the four main areas of basic research on homeopathy, as there are animal research, plant bioassays, in vitro models and physicochemical research, so that this catalogue should be feasible to all fields of research for authors writing their publications.
References 1 Witt C, Bluth M, Albrecht HT, Weißhuhn T, Baumgartner S, Willich S. The in vitro evidence for an effect of high homeopathic potencies e a systematic review of the literature. Complementary Ther Med 2007; 15(2): 128e138. 2 Schulte J. About quality and standards in ultra high dilution research and research on homeopathy. In: Endler PCSJ (ed). Ultra High DilutiondPhysiology and Physics. Dordrecht, The Netherlands: Kluwer Academic Publishers, 1994, pp 171e176. 3 Linde W, Melchart D, Jonas W, Hornung J. Ways to enhance the quality and acceptance of clinical and laboratory studies in homoeopathy. Br Homoeopath J 1994; 83(1): 3e7. 4 Baumgartner S, Heusser P, Thurneysen A. Methodological standards and problems in preclinical homoeopathic potency research. Forsch Komplementarmedizin Klass Naturheilkd 1998; 5(1): 27e32. 5 Linde K, Jonas W, Melchart D, Worku F, Wagner H, Eitel F. Critical review and meta-analysis of serial agitated dilutions in experimental toxicology. Hum Exp Toxicol 1994; 13(7): 481e492. 6 Becker-Witt C, Weißhuhn T, L€ udtke R, Willich S. Quality assessment of physical research in homeopathy. J Altern Complementary Med 2003; 9(1): 113e132. 7 Linstone H, Turoff M. The Delphi method: techniques and applications, http://www.is.njit.edu/pubs/delphibook/; 2002. 8 Stock-Schr€ oer B, Albrecht H, Betti L, et al. Reporting experiments in homeopathic basic research (REHBaR) e description of the checklist development. eCAM 2009; http://dx.doi.org/10.1093/ecam/nep170. 9 Stock-Schr€ oer B, Albrecht H, Betti L, et al. Reporting Experiments in Homeopathic Basic Research (REHBaR) e a guideline for authors. Homeopathy 2009; 98: 287e298.
Homeopathy Please cite this article in press as: Stock-Schr€oer B, Reporting Experiments in Homeopathic Basic Research (REHBaR), Homeopathy (2015), http:// dx.doi.org/10.1016/j.homp.2015.06.006