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Homeopathy is a system of therapeutics that treats disease with highly diluted substances based on the Law of Similars, which holds that “like cures like.” Despite widespread use, homeopathy lacks a comprehensive and robust evidence base.We examined the state of homeopathic clinical research by critically assessing the overall quality of peer-reviewed, recently published, English-language, homeopathic clinical research in terms of internal, external, and model validity using standard and homeopathic-specific instruments. Further, we convened an international panel of nine experts in research methods and homeopathy to identify gaps in homeopathic research and prioritize areas for future study.We reviewed 99 clinical research studies targeting a wide range of populations and conditions. Studies were conducted in Western and Asian countries, with the largest number (30 percent) conducted in India. Of the 99 studies reviewed, 85 were controlled trials; 79 of these were randomized. There were many areas where the quality of the studies could be improved. About two-thirds of the 85 controlled trials had either high (42 percent) or unclear (24 percent) risk of bias according to internationally recognized standards for internal validity. Of the 14 observational (cohort) studies, over one-third did not control for important confounders in the outcome analyses. Regarding external validity, adherence was reported in less than a third of studies (n=31). Forty percent of studies (79 % of observational studies) did not report on safety. Regarding model validity, fewer than two-thirds of the studies were consistent with homeopathic principles.Our expert panel was mixed on whether the homeopathic research literature was missing important populations and/or conditions, and they suggested a variety of priority areas. Panelists also expressed a variety of opinions about the types of homeopathy that should be prioritized for future study but also noted that since homeopathic practice differs by country, each country may have different priorities.Panelists agreed with the findings of the literature review that the research literature was at least somewhat deficient in all three types of validity. Although our assessment of validity was [by necessity] based only on what was reported, this assessment suggests the need for both better reporting and higher quality research. They recommended the use of reporting guidelines to improve all types of validity, the identification of exemplar studies to help guide researchers to improve internal validity, and, given the limitations of the instruments available to measure external and model validity, that these instruments be validated and configured to provide summary scores. Finally, substantial discussion addressed the need to bring more research expertise into homeopathic studies, both by better training homeopathic researchers and by collaborating with experienced conventional medicine research groups.

Abstract Background The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review. Methods We searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion. A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript. Results Eighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of −0.23 (95 % confidence interval (CI) −0.45 to −0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93–1.15] or SAEs (RR [95 % CI] 1.39 [0.78–2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions. Conclusions Trials show a small but significant effect of HA on function on which recent systematic reviews agree, but lack of AE synthesis standardization leads to opposite conclusions about the balance of benefits and harms. A limitation of the re-analysis of the prior systematic review is that it required imputation of missing data.