Abstract:Since the inception of homoeopathy by Dr. Hahnemann who himself “re-searched” into the history to prove the theories he discovered, there are several research papers published in homoeopathy. Currently, the greatest weaknesses in homoeopathic research are the variety of unreplicated studies and the small sample sizes. Hence, there is a need for use of appropriate research methodology, following guidelines for conducting research, use of validated tools and Multi-site research studies with larger sample sizes.
Key words: Research orientation, Homoeopathy, HOM-CASE
Abbreviations: RCT- randomised controlled trial, HPT- homoeopathic pathogenetic trial
The homoeopathic sector has begun to realise the need for scientific research. Research orientation is what we need today, as we talk of scientific evidence-based medicine.
An authoritative paper concluded that ‘the evidence of the effectiveness of homoeopathy for specific clinical conditions is scant, is of uneven quality, and is generally of poorer quality than research done in allopathic (mainstream) medicine.’ Nevertheless ‘when only high-quality studies have been selected… a surprising number show positive results’ although ‘even the best systematic reviews cannot disentangle components of bias in small trials.’ These authors conclude that ‘more and better research is needed, unobstructed by belief or disbelief in the system.’ 
Despite 200 years of practise of homoeopathy and several recent studies documenting homoeopathic treatment effects under double-blind conditions, the medical and scientific community has generally dismissed these findings because of a lack of a plausible mechanism for the observed effects. 
The report states that clinical trials done for evaluation of homoeopathy, taken in their totality, are most consistent with nonspecific effects and placebo responses. 
This can be, as the success of any clinical trial depends on the prescriber, the skills to individualise and prescribe the simillimum, i.e. the individualised medicine in homoeopathy. Prescriptions without justifications in clinical trials lead to questionable results.
So now, trial designs must be revisited in homoeopathy. The focus must be being laid on personalized medicine  and scientific tools for assessing the reliability and validity of homoeopathic trials 
Emphasis must be made on selecting the research study.
- Descriptive study
- Case study / case report
Case reports are considered the first step to demonstrate evidence-based medicine. A case report should be a unique clinical experience in terms of diagnosis, investigations, or management that widens the scope of homoeopathy.
Each peer-reviewed journal in homoeopathy has a section where case reports are included. The Indian Journal of Homoeopathy has given a template for Case Reports.
For Example, A 15-mm urinary calculus expelled with homoeopathic medicine – A case report by Rai S and Vineetha K R published in Indian J Res Homoeopathy 2021;15:155-61 
CARE guidelines had been evolved for writing case reports. Van Haselen, using the Delphi technique with a panel of 19 homoeopathic experts, suggested modifications in the CARE case report guidelines for writing homoeopathic case reports. He has recommended using these HOM-CASE guideline extensions to improve the quality of homoeopathic case reports. 
- Case series
A case series (also known as a clinical series) is a type of medical research study that tracks subjects with a known exposure, such as patients who have received a similar treatment,  or examines their medical records for exposure and outcome. Case series may be consecutive  or non-consecutive,  depending on whether all cases presenting to the reporting authors over a period were included, or only a selection.
For example, Homoeopathic management of wrist ganglion: A Case series published in Indian J Res Homoeopathy 2021; by Nath and Palit DK. 
- Cross-sectional survey
A cross-sectional survey collects data to make inferences about a population of interest (universe) at one point in time. 
For example, An online cross-sectional survey on knowledge, attitudes, practices, and perspectives of homoeopathic practitioners towards COVID-19 by Taneja D and Khurana A published in Indian J Res Homoeopathy 2020;14:90-9.
- Analytical study
studies: The three classical types of observational studies in research are –
studies: In cohort studies, a cohort, i.e., a group of people with some
similarity, e.g., in treatment, diagnosis, or location, is followed up and
systematically observed within a given timeframe.
- Prospective cohort study: The study begins with a baseline assessment at the starting time point and progresses into the future with follow-up assessments of data.
- Retrospective cohort study: The data are collected only from already extant records. The outcome has already occurred and is assessed retrospectively.
- Cohort studies: In cohort studies, a cohort, i.e., a group of people with some similarity, e.g., in treatment, diagnosis, or location, is followed up and systematically observed within a given timeframe.
- Observational studies: The three classical types of observational studies in research are –
For Example, A cohort study by Witt et al, which included nearly 4000 new patients undergoing homoeopathic case taking and followed up this cohort for 8 years. This study allowed observation of who consulted a homoeopathic physician, how frequently the consultations took place, which remedies and potencies were prescribed, the intensity of complaints and quality of life changed over time. [14, 15]
- Case-control: The researcher identifies an existing health problem (“cases”) and a similar group without the problem (“controls”) and then compare them retrospectively concerning exposure. 
For example, A study trying to show that people who smoke (the attribute) are more likely to be diagnosed with lung cancer (the outcome), the cases would be persons with lung cancer, the controls would be persons without lung cancer (not necessarily healthy), and some of each group would-be smokers.
There are guidelines and tools relevant for homoeopathy that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE, and the ENCePP Guide. 
- Interventional studies
Interventional study designs, also called experimental study designs, are those where the researcher intervenes at some point throughout the study.
- Control trial: Controlled trials allow discrimination of the patient outcome from an outcome caused by other factors (such as natural history or observer or patient expectation). The different types of control trials are:
- Placebo control helps to discriminate outcomes due to intervention (new product) from outcomes due to other factors. This design is used to demonstrate superiority or equivalence. There are many homoeopathic research papers published using placebo control trials. While conducting a homoeopathic pathogenetic trial (HPT), a placebo control trials can be used to elicit the pathogenetic effects of the homoeopathic preparation vs placebo. 
- “No treatment” concurrent control – No intervention will be administered in the control arm in this design. Study endpoints must be objective in this design.
- Active treatment concurrent control – This design involves the comparison of a new drug to a standard drug or compare a combination of new and standard therapies vis a vis standard therapy alone.
- Historical control (external and non-concurrent) – sources of controls are external to the present study and were treated at an earlier time (earlier therapeutic gold standard) or in a different setting. [19,20]
- Randomized control trial: In randomised controlled trials, trial participants are randomly assigned to either treatment or control arms.
- Parallel group trial design: In this design, subjects are randomized to one or more study arms and each study arm will be allocated a different intervention. After randomization, each participant will stay in their assigned treatment arm for the duration of the study.
- Cross over design: In this design, some participants start with drug A and then switch to drug B (AB sequence) in one trial arm, while subjects in other trial arm start with drug B and then switch to drug A (BA sequence). An adequate washout period must be given before crossover to eliminate the effects of the initially administered intervention. Outcomes are then compared within the same subject (effect of A vs. effect of B). This study has a limitation, as it is difficult to decide the washout period of Homoeopathic medicine.
Blinding in randomised controlled trial if withholding the treatment arm from individuals involved in the study. Blinding within randomised controlled trial includes patient blinding, provider blinding, or assessor blinding. [19, 20]
- A randomized controlled trial in the management of alcohol dependence: Homoeopathic vs. standard Allopathic treatment, conducted by Central Council for Research in Homoeopathy, published in Indian J Res Homoeopathy 2014;8:187-93 
- Effects of individualized homoeopathic intervention in Stage I essential hypertension: A single-blind, randomized, placebo-controlled trial, conducted by Dr. Roja Varanasi and others, published in Indian J Res Homoeopathy 2020;14:3-14 
There are standards and guidelines to systematize and elevate the quality of interventional research design, execution, and reporting, such as CONSORT.
The main problem of randomised controlled trial in homoeopathy is that it is not personalised and personalised medicine is the essence of homoeopathy.
- Systematic reviews and meta-analysis
Systematic reviews, as the name implies, typically involve a detailed and comprehensive plan and search strategy derived a priori, intending to reduce bias by identifying, appraising, and synthesising all relevant studies on a particular topic. 
Meta-analysis is a quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research. 
- Veterinary Homoeopathy: Systematic Review of Medical Conditions Studied by Randomised Placebo-Controlled Trials, by Mathie RT, Clausen J, published in The Veterinary Record, Volume 175, Issue 15, 2014, Pages 373-381. 
- Randomised Placebo-Controlled Trials of Individualised Homoeopathic Treatment: Systematic Review and Meta-Analysis, by Mathie RTet.al., published in Systematic Reviews, Volume 3, Issue 1, 2014, Page 142.
Meta‑analysis conducted using these Randomized Control Trails is criticized for ‘cherry‑picking’ of studies, disputed selection criteria and purposeful exclusion of studies. 
Problem with meta-analysis in homoeopathy: It reflects the point of view that the treatment with a specific remedy could be administered in a particular disease. However, homoeopathy aims to treat the whole person, rather than the diseases and each case has to be treated individually with an individualized remedy. Furthermore, the commonly known events during the course of homoeopathic treatment, such as “initial aggravation” and “symptom-shift” were not considered in almost all the studies. Thus, only few trials were eligible for meta-analyses, if at all. 
There are standard guidelines for reporting systematic reviews and meta-analysis such as PRISMA, 
There is a need for “re-search” and “re-validation” of the existing work, by following the guidelines given for each research study and using validated tools.
Research studies must be taken on a larger sample size and at multi-centric levels.
There must be a Centralized database of research activities accessed globally, Observational studies, Systematic reviews and High-quality clinical trials and verification must be encouraged.
- Jonas WB, Kaptchuk TJ, Linde K, A critical overview of homoeopathy, Ann Intern Med. 2003 Mar 4; 138(5):393-9.
- Rutten L, Mathie RT, Fisher P, Goossens M, van Wassenhoven M (2012) Plausibility and evidence: the case of homoeopathy. Med Health Care Philos.
- (2010) ‘Evidence Check 2: Fourth Report of Session 2009-10’; Science and Technology Committee Homoeopathy House of Commons; Authority of the House of Commons, London: The Stationery Office Limited Published: 18, 21,130,144.
- Vaidyanathan G. Redefining clinical trials: The age of personalized medicine. Cell 2012;148:1079‑80.
- Mathie RT, Roniger H, Van Wassenhoven M, Frye J, Jacobs J, Oberbaum M, et al. Method for appraising model validity of randomised controlled trials of homoeopathic treatment: Multi‑rater concordance study. BMC Med Res Methodol 2012;12:49
- Rai S, Vineetha K R. A 15-mm urinary calculus expelled with homoeopathic medicine – A case report. Indian J Res Homoeopathy 2021;15:155-61
- Van Haselen RA. Homoeopathic clinical case reports: Development of a supplement (HOM-CASE) to the CARE clinical case reporting guideline. Complement Ther Med 2016; 25:78-85
- “Definition of case series – NCI Dictionary of Cancer Terms”.
- “Definition of consecutive case series – NCI Dictionary of Cancer Terms”.
- “Definition of nonconsecutive case series – NCI Dictionary of Cancer Terms”.
- Nath A, Palit DK. Homoeopathic management of wrist ganglion: Case series. Indian J Res Homoeopathy 2021;15:137-46
- Paul J. Lavrakas, Cross-Sectional Survey Design, In: Encyclopedia of Survey Research Methods, Sage research methods, 2008, DOI: https://dx.doi.org/10.4135/9781412963947.n120
- Taneja D, Khurana A. An online cross-sectional survey on knowledge, attitudes, practices and perspectives of homoeopathic practitioners towards COVID-19. Indian J Res Homoeopathy 2020;14:90-9
- Witt CM, Lüdtke R, Baur R, Willich SN. Homoeopathic medical practice: long-term results of a cohort study with 3981 patients. BMC Public Health 2005;5:115
- Witt CM, Lüdtke R, Mengler N, Willich SN. How healthy are chronically ill patients after eight years of homoeopathic treatment?–Results from a long term observational study BMC Public Health 2008;8:413
- Witt C, Linde K. Clinical Research in Complementary and Integrative Medicine. Munich: Elsevier; 2011
- Michael Teut, et.al., Recommendations for Designing, Conducting and Reporting Observational Studies in Homoeopathy, Homoeopathic Links 2020, 109:114–125. https://doi.org/10.1055/s-0040-1708045.
- Mohanty N, Choudhury SK, Jena SK. A double-blind, placebo-controlled Homoeopathic Pathogenetic Trial of Nanocurcumin 6X. Indian J Res Homoeopathy 2015;9:176-87
- Brijesh Nair, Clinical Trial Designs, Indian Dermatology Online J. 2019 Mar-Apr; 10(2): 193–201. doi: 10.4103/idoj.IDOJ_475_18.
- Matthew S. Thiese, Observational and interventional study design types; an overview, Biochem Med (Zagreb). 2014 Jun; 24(2): 199–210. doi: 10.11613/BM.2014.022
- Varanasi R, Kolli R, Rai Y, Ramesh D, Kiranmayee R G, Chandra Reddy G R, Baig H, Patole T, Srivastava P, Bhalaerao R, Chaudhary A, Kumar A, Sarathy V, Jayasri G R, Sachdeva G, Jain SK, Sharma N, Amsole S, Oinam A, Oberai P, Manchanda RK. Effects of individualised homoeopathic intervention in Stage I essential hypertension: A single-blind, randomised, placebo-controlled trial. Indian J Res Homoeopathy 2020;14:3-14
- Central Council for Research in Homoeopathy. A randomized controlled trial in the management of alcohol dependence: Homoeopathic vs. standard Allopathic treatment. Indian J Res Homoeopathy 2014;8:187-93
- Lindsay S. Uman, Systematic Reviews and Meta-Analyses, J Can Acad Child Adolesc Psychiatry. 2011 Feb; 20(1): 57–59.
- A B Haidich, Meta-analysis in medical research, Hippokratia. 2010 Dec; 14(Suppl 1): 29–37.
- Mathie RT, Clausen J, Veterinary Homoeopathy: Systematic Review of Medical Conditions Studied by Randomized Placebo-Controlled Trials, The Veterinary Record, Volume 175, Issue 15, 2014, Pages 373-381.
- Mathie RT, Lioyd SM, Legg LA, Clausen J, Moss S, Davidson JR, Ford I, Randomised Placebo-Controlled Trials of Individualised Homoeopathic Treatment: Systematic Review and Meta-Analysis, Systematic Reviews, Volume 3, Issue 1, 2014, Page 142.
- Hahn RG. Homoeopathy: Meta‑analyses of pooled clinical data. Forsch
- Vithoulkas G. Serious mistakes in meta-analysis of homoeopathic research. J Med Life. 2017 Jan-Mar;10(1):47-49. PMID: 28255376; PMCID: PMC5304371.
- Arya S, Kaji AH, Boermeester MA. PRISMA Reporting Guidelines for Meta-analyses and Systematic Reviews. JAMA Surg. 2021; 156(8):789–790. doi:10.1001/jamasurg.2021.0546
About the author
Dr Neha Patel , MD, Assistant Professor, Smt C.M.P. Homoeopathic Medical College.