Homeopathic remedies for the treatment of osteoarthritis: a systematic review

Osteoarthritis is a common rheumatic disease. Limitations of conventional medical management of this condition indicate a real need for safe and effective treatment of osteoarthritic patients. The authors review the clinical evidence for and against the effectiveness of homeopathic medicines in the treatment of patients with osteoarthritis. A systematic review of all randomised controlled clinical trials of homeopathic treatment of patients with this condition is presented. A comprehensive search yielded four trials which are discussed in detail. The authors conclude that the small number of randomised clinical trials conducted to date, although favouring homeopathic treatment, do not allow a firm conclusion as to the effectiveness of homeopathic remedies in the treatment of patients with osteoarthritis. The clinical evidence appears promising, however, and more research into this area seems warranted.     

When and how should new therapies become routine clinical practice?

The process by which new therapies enter clinical practice is frequently suboptimal. Often, ideas for new therapies are generated by clinical observations or laboratory studies; therapies based on those ideas may enter clinical practice without any further scrutiny. As a consequence, some ineffective practices become widespread. This article proposes a six-stage protocol for the implementation of new therapies. Hypotheses about therapy based on preclinical research should be subject to clinical exploration and pilot studies prior to rigorous assessment with randomised clinical trials. If randomised clinical trials suggest that the intervention produces clinically important effects, further randomised studies can be conducted to refine the intervention. New interventions should not be recommended, or included in teaching curricula, or taught in continuing education courses until their effectiveness has been demonstrated in high-quality randomised clinical trials.     

Clinical review: Therapy for refractory intracranial hypertension in ischaemic stroke

The treatment of patients with large hemispheric ischaemic stroke accompanied by massive space-occupying oedema represents one of the major unsolved problems in neurocritical care medicine. Despite maximum intensive care, the prognosis of these patients is poor, with case fatality rates as high as 80%. Therefore, the term 'malignant brain infarction' was coined. Because conservative treatment strategies to limit brain tissue shift almost consistently fail, these massive infarctions often are regarded as an untreatable disease. The introduction of decompressive surgery (hemicraniectomy) has completely changed this point of view, suggesting that mortality rates may be reduced to approximately 20%. However, critics have always argued that the reduction in mortality may be outweighed by an accompanying increase in severe disability. Due to the lack of conclusive evidence of efficacy from randomised trials, controversy over the benefit of these treatment strategies remained, leading to large regional differences in the application of this procedure. Meanwhile, data from randomised trials confirm the results of former observational studies, demonstrating that hemicraniectomy not only significantly reduces mortality but also significantly improves clinical outcome without increasing the number of completely dependent patients. Hypothermia is another promising treatment option but still needs evidence of efficacy from randomised controlled trials before it may be recommended for clinical routine use. This review gives the reader an integrated view of the current status of treatment options in massive hemispheric brain infarction, based on the available data of clinical trials, including the most recent data from randomised trials published in 2007.     

Randomised studies in general practice: how to integrate the electronic patient record

The 'randomised database study' strategy was first proposed in 1997, with the aim of combining the generalisability of observational database studies based on electronic patient records (EPRs) with the validity of randomised clinical trials (RCTs). The key feature was to randomly assign treatments and to use routine care data, as available in the observational database, for patient identification and follow-up. To our knowledge, however, the idea of the randomised database study has not been implemented yet. The conduct of a randomised study in an observational database requires adjustments to methods of medical information processing in the general practice. We developed a software system that facilitates the conduct of an RCT with observational databases based on EPRs. It identifies eligible subjects and presents them one by one to the physician once their EPR is accessed. The general practitioner can then start an interactive recruitment process; after completion, the computer randomises the patients. Follow-up is documented by normal routine care in the EPR. Although the randomised database study has many methodological advantages, it has never been tested. Our software system is meant as a tool to implement and facilitate evaluation of the randomised database approach.     

The research evidence base for homeopathy: a fresh assessment of the literature

BACKGROUND: The claims made for the clinical effects of homeopathy are controversial. The results of several meta-analyses of clinical trials are positive, but they fail in general to highlight specific medical conditions that respond well to homeopathy. AIMS: This review examines the cumulative research from randomised and/or double-blind clinical trials (RCTs) in homeopathy for individual medical conditions reported since 1975, and asks the question: What is the weight of the original evidence from published RCTs that homeopathy has an effect that is statistically significantly different from that in a comparative group? METHOD: Analysis of the 93 substantive RCTs that compare homeopathy either with placebo or another treatment. RESULTS: 50 papers report a significant benefit of homeopathy in at least one clinical outcome measure, 41 that fail to discern any inter-group differences, and two that describe an inferior response with homeopathy. Considering the relative number of research articles on the 35 different medical conditions in which such research has been carried out, the weight of evidence currently favours a positive treatment effect in eight: childhood diarrhoea, fibrositis, hayfever, influenza, pain (miscellaneous), side-effects of radio- or chemotherapy, sprains and upper respiratory tract infection. Based on published research to date, it seems unlikely that homeopathy is efficacious for headache, stroke or warts. Insufficient research prevents conclusions from being drawn about any other medical conditions. CONCLUSIONS: The available research evidence emphasises the need for much more and better-directed research in homeopathy. A fresh agenda of enquiry should consider beyond (but include) the placebo-controlled trial. Each study should adopt research methods and outcome measurements linked to a question addressing the clinical significance of homeopathy's effects.     

Reported challenges in nurse-led randomised controlled trials: an integrative review of the literature

Scand J Caring Sci; 2011; 25; 194–200
Reported challenges in nurse‐led randomised controlled trials: an integrative review of the literature Aims: The purpose of this integrative literature review was to explore and discuss the methodological challenges nurse researchers report after conducting nurse‐led randomised controlled trials in clinical hospital settings. Our research questions were (i) what are the most commonly experienced methodological barriers and challenges and (ii) which lessons can be learned from these reports? Method: A database search of Medline, Cinahl, The Cochrane Library and Embase was carried out. Variants of the following search terms were used: randomised controlled trial, controlled clinical trial, clinical trial, methods, nursing research, nursing, research, challenges, barriers, nurse’s role, nurse attitude, attitude of health personnel. Findings: The literature on reported challenges and barriers between 1999 and 2009 showed that the most often experienced problems were (i) sufficient patient recruitment, (ii) nonadherence to research protocols and (iii) economic and organisational obstacles. These three challenges and barriers were inter‐related and all were affected by time and timing. Conclusion: Randomised controlled trials are complex, expensive, time‐consuming and highly demanding for researchers and the clinical nursing staff. Two lessons learned from this integrative review can be highlighted. First, we recommend researchers openly to share their experiences of barriers and challenges. They should describe factors that may have inhibited the desired outcome. Second, efforts to improve the collaboration between nurse researchers and clinicians, including education, training and support may increase the success rate and quality of nurse‐led studies using the randomised controlled trial.     

Homeopathy for anxiety and anxiety disorders: a systematic review of the research

OBJECTIVE: To conduct a systematic review of the clinical research evidence on homeopathy in the treatment of anxiety and anxiety disorders. METHODS: A comprehensive search of major biomedical databases: MEDLINE, EMBASE, ClNAHL, PsycINFO, Cochrane Library; and of specialist complementary and alternative medicine (CAM) databases: AMED, CISCOM and Hom-Inform was conducted. Efforts were made to identify unpublished and ongoing research using relevant sources and experts in the field. Relevant research was categorised by study type and appraised according to study design. Clinical commentaries were obtained for studies reporting clinical outcomes. RESULTS: Eight randomised controlled studies were identified. The types of anxiety and anxiety disorders studied were test anxiety, generalised anxiety disorder and anxiety related to medical or physical conditions such as cancer or surgical procedures. Single case reports/studies were the most frequently encountered study type but other study types including uncontrolled trials/case series and surveys were also found. No relevant qualitative research was identified. CONCLUSIONS: A comprehensive search demonstrates that the evidence on the benefit of homeopathy in anxiety and anxiety disorders is limited. A number of studies of homeopathy in such conditions were located but the randomised controlled trials report contradictory results, are underpowered or provide insufficient details of methodology. Several uncontrolled and observational studies reported positive results including high levels of patient satisfaction but because of the lack of a control group, it is difficult to assess the extent to which any response is due to homeopathy. Adverse effects reported appear limited to 'remedy reactions' and included temporary worsening of symptoms and reappearance of old symptoms. On the basis of this review it is not possible to draw firm conclusions on the efficacy or effectiveness of homeopathy for anxiety. However, surveys suggest that homeopathy is quite frequently used by people suffering from anxiety. If shown to be effective, it is possible that homeopathy may have benefits in terms of adverse effects and acceptability to patients. Consequently, further investigation is indicated. Future research should be of pragmatic design and include qualitative studies.     

Qualitative methods in end-of-life research: recommendations to enhance the protection of human subjects

Qualitative research has the potential to contribute important new knowledge to care near the end of life, but research is often hampered by questions about how best to protect dying patients and their family members who serve as research subjects. Due to lack of familiarity with the techniques of ethnographic or observational research, as well as concerns about the vulnerability of the dying, members of Institutional Review Boards (IRBs) are often unable to evaluate the benefits and potential harms of studies. In addition, policies derived from standards based on interventional medical research or clinical trials may be applied inappropriately. We offer comprehensive recommendations aimed at improving the translation of human subjects guidelines into meaningful protections for subjects in qualitative studies, including education for IRBs. Policies must be flexible and should be guided by empirical findings documenting the actual impact of research participation, rather than a priori assumptions about patient vulnerability. Sensitive topics, such as drug use, may require added protections.     

Clinical trials in very elderly people: the point of view of geriatricians

BACKGROUND: Very elderly subjects (aged > or =80 years) and polypathological elderly subjects experience frequent and serious adverse drug effects. They are nevertheless still excluded from clinical research. METHODS: We questioned geriatricians through a questionnaire about the usefulness and feasibility of randomised controlled trials (RCTs) in this population. RESULTS: Forty-eight percent of geriatricians questioned did participate in RCTs, but 96.8% considered that RCTs including very elderly subjects were scientifically necessary. Among geriatricians who never participated in RCTs, 36% were never contacted regarding participation in such clinical research. The most important difficulties in developing RCTs in very elderly subjects were methodological difficulties (narrow eligibility criteria incompatible with patient heterogeneity) and those associated with patient consent. For 38.2% of the geriatricians, the fact that pharmaceutical companies are under no obligation to promote RCTs in very elderly subjects represents a major obstacle in the development of such RCTs. CONCLUSIONS: The development of RCTs involving very elderly subjects depends first on a political choice, together with an adapted regulatory framework.     

Ethical issues in administrative continuous improvement. Applying the concept of prior notification to the conduct of firm trials

Consensus exists concerning the distinctions to be drawn between clinical practice and research. When the latter is undertaken, established regulations require that protocols including plans for obtaining subjects' informed consent be submitted to Institutional Review Boards for approval. Less consensus or codification exists concerning evaluations conducted by managers in health care settings. The recent development of firm systems, in which randomized, controlled designs are employed to evaluate administrative interventions, provides a unique context in which to consider whether the subjects of administrative evaluations should be afforded protections granted subjects of clinical research. Accordingly, the history of firm trials from an ethical perspective is reviewed. At the University of Washington, participants of such studies are informed through the process of prior notification, an adaptation of procedures employed widely to inform patients that records or specimens may be used in epidemiologic or biomedical research. Prior notification appears to be a useful refinement of the firm system methodology, one that may have application to managerial manipulations in other arenas.     

Survival analysis

Aims and objectives. This paper describes when and why survival analysis is used and describes the use and interpretation of the techniques most commonly encountered in medical literature. This is performed using examples taken from core medical journals. Background. Survival analysis is widely used in clinical and epidemiological research: in randomised clinical trials for comparing the efficacy of treatments and in observational (non-randomised) research to determine and test the existence of epidemiological association. Design. This paper introduces the principles, practice and terminology of survival analysis. Methods. References are made to examples from open-access medical journals. Results. Survival analysis is a well-established series of methodologies that are widely encountered in medical literature for both observational and randomised studies. Conclusions. Survival analysis represents a more efficient use of clinical data than other forms of analysis which rely on fixed time periods. One of the most widely used techniques is that developed by Kaplan and Meier. This involves the creation of life tables and the plotting of survival curves with comparison made between two or more groups. The log-rank test is commonly used to establish whether there is a statistically significant difference between these groups. The Multivariate Cox proportional hazards extend this approach to give an estimate of effect size (the Hazards Ratio) and can adjust for any potential confounding variables. In this model, the assumption of proportional hazards is of key importance and should always be checked. More advanced techniques are the use of time-dependent variables and the less widely used parametric survival techniques. Care should always be taken when considering the assumptions involved when using such methods. Relevance to clinical practice. As survival analysis is widely used in clinical research, it is important that readers can critically evaluate the use of this technique.     

Gene therapy as a novel therapeutic option in the treatment of peripheral vascular disease: systematic review and meta-analysis

Background: Stimulation of therapeutic angiogenesis using gene therapy is a novel intervention for peripheral vascular disease (PVD). Despite encouraging outcomes from animal studies and phase 1 trials, results from larger trials in this area have been conflicting. We undertook a systematic review and meta‐analysis of randomised controlled trials in this field, to clarify the current situation. Methods: Medline, Embase, trial registries, the American Heart Association (AHA) abstract database and article reference lists were searched to identify randomised controlled trials of gene therapy for treatment of PVD. The outcomes were change in peak walking time and claudication onset time at 90 and 180 days post‐treatment, and change in ankle‐brachial pressure index (ABPI) at 90 days. Weighted mean differences (WMD) were calculated for these outcomes. Results: Five eligible randomised clinical trials were identified, containing 508 patients. There were no significant differences between control and intervention groups for any outcomes, irrespective of whether low‐dose or high‐dose gene therapy was tried. Conclusion: The available data suggests that gene therapy confers no benefit on patients with PVD. Closer examination of the individual trials shows that several have an excessive placebo response, which may go some way to explaining our result. Further research in this area in needed.     

Adaptive designs, informed consent, and the ethics of research

The ethical tension in research design is often characterized as that between individual and collective ethics. While adaptive clinical trials (ACTs) are generally considered to be more sensitive to individual ethics, the concomitant loss of statistical power associated with them is often used to justify randomized clinical trials (RCTs). This paper challenges this characterization of the central ethical problem in research design. It argues that the key consideration in clinical research hinges on the process of informed consent. When the research context is such that the subject is able to provide informed consent, RCTs can be justified and may be required. However, in desperate medical situations the process of informed consent is often undermined. It is argued that in such situations ACTs are ethically required. We introduce "the principle of interchangeability" and argue that it must be satisfied if research in desperate medical situations is to be justified.     

Randomised controlled trials in nursing and midwifery: an interview with Maralyn Foureur. Interview by Pamela J. Wood

Randomised controlled trials are considered to be one of the best research designs for determining effective care in the clinical setting. Relatively few randomised controlled trials, however, have been carried out in nursing or midwifery practice, so few examples of the practical realities of this research methodology are readily accessible. This is the sixth article in a series based on interviews with nursing and midwifery researchers, designed to offer the beginning researcher a first-hand account of the experience of using particular methodologies. This article focuses on the randomised controlled trial as experienced by Maralyn Foureur (RGON, RM, BA, Grad Dip Clin Epidem, PhD) who used this methodology to demonstrate the effectiveness of a continuity of care model in midwifery practice.     

Synthesis of researcher reported strategies to recruit adults of ethnic minorities to clinical trials in the United Kingdom: A systematic review

BackgroundPeople from ethnic minorities are reported to have higher rates of physical illness (diabetes and ischemic heart disease) and mental disorders. Disparities relate not just to diagnosis, but also to care pathways and treatment outcomes. Despite this, they are underrepresented in clinical research. This reduces the generalisability of research findings across multi ethnic populations and hinders the development of accessible services. Researchers often face difficulties in recruiting ethnic minority participants to clinical research due to low levels of cultural competence and limited resources. There are few published trials focusing on ethnic minorities in the UK and we need to understand what recruitment strategies have already been implemented and recommended when recruiting ethnic participants. This will help researchers in applying these lessons to future clinical trials.MethodTo identify strategies for recruiting ethnic minorities to clinical trials in the UK a systematic review of published randomised controlled trials (RCT) exclusively targeting ethnic minorities was conducted. Multiple databases were searched by combining the terms “ethnic minorities”, “randomised controlled trials” and “United Kingdom”. Data was extracted on recruitment strategies described by each RCT and then themes were created.ResultsTwenty-one included RCT's identified various strategies to recruit ethnic communities to clinical trials. These have been described under three overarching themes; adaptation of screening and outcome measures, culturally specific recruitment training and recruitment processes.ConclusionThe review highlighted that researchers employed limited strategies to enhance the recruitment level. The full extent of the use of strategies was not described well in the publications. There is a need for wider training and support for the trialist to enhance and build up recruitment skills to facilitate the recruitment of ethnic minorities to clinical trials.     

A systematic review of the effectiveness of cutaneous warming systems to prevent hypothermia

Aims. To retrieve and critique recent randomised trials of cutaneous warming systems used to prevent hypothermia in surgical patients during the intraoperative period and to identify gaps in current evidence and make recommendations for future trials. Background. Hypothermia affects up to 70% of anaesthetised surgical patients and is associated with several significant negative health outcomes. Design. Systematic review using integrative methods. Methods. We searched CINAHL, EMBASE, Cochrane Register of Controlled Trials and Medline databases (January 2000–April 2007) for recent reports on randomised controlled trials of cutaneous warming systems used with elective patients during the intraoperative period. Inclusion criteria. We included randomised control trials examining the effects of cutaneous warming systems used intraoperatively on patients aged 18 years or older undergoing non‐emergency surgery. Studies published in English, Spanish or Portuguese with a comparison group that consisted of either usual care or active cutaneous warming systems without prewarming were reviewed. Results. Of 193 papers initially identified, 14 studies met the inclusion criteria. There was moderate evidence to indicate that carbon‐fibre blankets and forced‐air warming systems are equally effective and that circulating‐water garments are most effective for maintaining normothermia during the intraoperative period. Few trials reported costs. Conclusions. Carbon‐fibre blankets and forced‐air warming systems are effective and circulating‐water garments may be preferable. Future research should measure the direct and indirect costs associated with competing systems. Relevance to clinical practice. Nurses can use this review to inform their selection of warming interventions in perioperative nursing practice. They can also assess other factors such as nursing workload, staff training and equipment maintenance, which should be incorporated into future research.     

Oscillatory effects in a homeopathic clinical trial: an explanation using complexity theory,and implications for clinical practice

Four double-blind, randomised, placebo-controlled clinical trials of asthma or rhinitis treated with homeopathic immunotherapy (HIT) at a 30C potency have been published. The most recent study, involving house dust mite allergic asthmatics, failed to confirm a therapeutic improvement at the end of the study, but did provide preliminary evidence for an oscillation in outcome (both physiological and subjective) in with verum treatment to placebo. In this paper we show how such an oscillation is consistent with a complexity theory interpretation of how the body functions as a whole, and speculate on why different studies have produced different results. If the complexity theory interpretation is correct, then this will have a significant impact on the design of clinical trials in homeopathy and, possibly, other complementary medical interventions.     

State of the controlled clinical trial enterprise in the United States

We undertook a survey of the current capability in the United States to conduct controlled clinical trials. The intention was to use the results as a foundation for understanding how to create a controlled clinical trial capability sufficient to meet future needs of US health care. For this purpose, using the results from an advanced search of ClinicalTrials.gov on 16 August 2009, we created a database consisting of actively recruiting interventional trials having at least one US investigator center. As of 16 August 2009, there were 10,974 actively recruiting interventional trials having at least one investigator center in the United States. These trials were seeking to recruit a total of 2.8 million subjects. Of the trials, 68% involved the study of drugs or biologicals. The data indicate that clinical research conducted in the United States is dominated by research on regulated products. We estimated that 1 of every 200 persons in the United States would need to participate as a subject in a clinical trial if the current clinical research portfolio is to be successfully completed.     

Nurse- and midwife-led trials in Australia and New Zealand: Scoping review protocol

BackgroundResearch led by nurses or midwives has the potential to successfully address current issues in clinical care. High-quality randomised controlled trials are needed to inform evidence-based practice; however, nursing and midwifery research has commonly been nonexperimental. Two connected scoping reviews of nurse- and midwife-led randomised controlled trials within Australia and New Zealand will be conducted to highlight potential research directions and identify resources for future research.AimThe purpose of the two reviews is to map the number and types of randomised controlled trials led by nurses or midwives within Australia and New Zealand.MethodsThe concept of interest is randomised controlled trials with a lead principal investigator holding nursing or midwifery credentials. The lead principal investigator must report an institutional affiliation in Australia or New Zealand, and the trial must recruit at a minimum of one site in Australia or New Zealand. Searches for academic literature will be conducted using Pubmed, Emcare, and Scopus. Sources for grey literature will include the Australian New Zealand Clinical Trials Registry, and grant outcomes published by the National Health and Medical Research Council, Medical Research Future Fund, and Health Research Council of New Zealand. Data analysis and presentation will be conducted separately for each review.DiscussionThese reviews will comprehensively map the experimental research activity of nurses and midwives within Australia and New Zealand and highlight potential research directions. From this, strategies to facilitate high quality nurse- and midwife-led trials can be developed, which are vital for informing evidence-based practice.