Homeopathic remedies for preventing and treating acute respiratory tract infections in children
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To outline the efficacy of homeopathic remedies compared with placebo or conventional therapy in preventing and treating ARTIs in children.
Background
Description of the condition
Acute respiratory tract infections (ARTIs) are a major cause of morbidity and mortality worldwide; they are responsible for 20% of all deaths in children under five years of age (excluding neonates), with 90% of such deaths due to pneumonia (WHO 2005). On average, a child has about five to eight attacks of ARTIs annually and these are the most common infections experienced by healthy children, resulting in about 30% to 40% of all hospital admissions (WHO 2005).
ARTIs can be classified as upper respiratory tract infections (URTIs) or lower respiratory tract infections (LRTIs). The upper respiratory tract consists of the airways from the nostrils to the vocal cords in the larynx, including the paranasal sinuses and middle ear. The lower respiratory tract comprises the remainder of the airways from the trachea and bronchi to the alveoli. URTIs may include nasopharyngitis, laryngitis, pharyngotonsillitis and otitis media. LRTIs comprise of bronchiolitis, bronchitis and pneumonia. For the purpose of this review, we will continue to refer to both URTIs and LRTIs as one under the term ARTIs.
Description of the intervention
Complementary and alternative medicine (CAM) is becoming increasingly popular (Frenkel 2001). Homeopathy, one of the many widespread forms of CAM, is the art of treating patients based on the principles of 'similars' and 'dilutions' (Lee‐Treweek 2006).
Current conventional interventions to control both URTIs and LRTIs are based on basic health care and environmental health, such as the widespread use of vaccinations, use of simple case‐by‐case management to diagnose and promptly treat children with conventional pharmaceutical therapies and improvements in nutrition (Chen 2011). Conventional medical therapy for URTIs includes analgesics, decongestants, antihistamines, expectorants, various types of antibiotics and nutritional supplements (eTG 2010).
Homeopathic care, i.e. the holistic primary care role provided by a homeopath involving complex interventions that may range from reassurance to behavioural strategies to provision of a homeopathic remedy, is an alternative to conventional therapy (Linde 1997; Ludtke 2008; Rutten 2008; Shang 2005). When a homeopathic remedy is prescribed by a homeopath, an individual substance for treatment is selected based on a thorough assessment, including a comprehensive history of presenting symptoms and complaints. Homeopathic remedies are serial dilutions which involves vigorous shaking in between dilutions (potentisation) of a substance (such as a herb or trace element). This process is thought to imprint information from the diluted substance to the solvent (Schulte 1999). When assessing the evidence, it is therefore important to consider the effect of homeopathic remedies alone (administered by either a patient, a health professional or specifically a homeopath) versus 'homeopathic care' (administered by a homeopath using homeopathic principles) as described above (Linde 1997; Ludtke 2008; Rutten 2008; Shang 2005).
Homeopathic practitioners claim benefit, especially in the paediatric population and in particular when dealing with respiratory infections that account for the most common cause of morbidity in children. In addition, the current documented decrease in efficacy of antibiotics against respiratory illness, calls for new approaches to treat common respiratory infections (Fahey 1998).
How the intervention might work
The interventions considered in this review will include homeopathic remedies with single or multiple components initiated by homeopaths, or the use of homeopathic remedies initiated by someone other than a homeopath (health professional or patient).
The basic concept behind homeopathic remedies is 'similia similibus curentur' (like cures like) (Walach 2005). Practically, this means that a substance that causes symptoms in a healthy individual is the same substance that can cure symptoms in an ill patient.
There is debate as to whether or not homeopathy can be effective at all, as actual doses of homeopathic drugs are far below what is considered to have any medically quantifiable effect. The compounds involved in the remedies are highly diluted in either alcohol or water in a process called 'potentisation'. Here, the original substance is diluted 1 to 99 parts of water or alcohol, followed by a second dilution of 1 to 99 parts and so on until the process may occur more than 30 times before the final mixture is produced. In addition, between every dilution, the mixture must be shaken a set number of times in a particular manner as this is believed to lead to memory in the molecules and release the healing energy of the compounds, i.e. succussion (Ullman 2002). The compounds involved may be diluted based on a number of established potency scales such as the original described by Hahnemann as the centesimal or 'C scale' and more recent ones such as the D, Q or LM scales (Jonas 2003). These substances and the dilutional principle are based on beliefs that diluting and shaking imprints information into water and the lower the dose of the medication, the greater its effectiveness (Jonas 2003). For this reason, homeopathy still remains highly controversial as the key concepts governing this form of medicine are not consistent with the established laws of conventional therapeutics.
Why it is important to do this review
Homeopathy is a popular method of treatment for respiratory type illnesses but the effectiveness it offers and the potential side effects are not well researched.
Most analyses of the research on homeopathy have concluded that there is little or no evidence to support homeopathy as an effective treatment for any specific condition, based on flawed or inadequate studies conducted. Most have also failed to differentiate between the efficacy of nanopharmacological and behavioural components of homeopathic care. However, some individual observational studies, randomised, placebo‐controlled trials and laboratory research have reported positive effects (Ullman 2010). This variation and uncertainty in the efficacy of homeopathic remedies outlines the need for more research and analyses to be undertaken in this vastly growing field of CAM.
There are a limited number of studies and analyses available in comparison to conventional therapy and, hence, there is no structured, unbiased outline of homeopathic remedies that would serve as a guideline for practitioners interested in CAMs. A systematic review of the literature on the effects of homeopathic remedies and care in respiratory infections in children will inform consumers and practitioners on the evidence base for homeopathy and contribute to the development of comprehensive guidelines (including complementary treatment) for the management of respiratory tract infections in children.
Objectives
To outline the efficacy of homeopathic remedies compared with placebo or conventional therapy in preventing and treating ARTIs in children.
Methods
Criteria for considering studies for this review
Types of studies
Double‐blind, randomised controlled trials (RCTs) or double‐blind cluster‐RCTs that compare homeopathy with placebo or conventional treatments to prevent or treat ARTIs in children. N of 1 studies in which a single patient receives both the treatment and the control intervention (assigned in a randomly allocated sequence) will be included if randomisation and blinding is performed.
Types of participants
Children of either gender, aged 16 years and younger suffering from ARTIs. This will include children with other acute or chronic co‐morbidities and who are not immunodeficient.
Types of interventions
Oral individualised homeopathic preparations (both simple preparations, involving single substances or complex preparations involving more than one substance) targeting ARTIs compared with standard treatments currently used clinically to treat various ARTIs, such as antihistamines, decongestants, analgesics, antibiotics and combinations of these treatments, or placebo.
We will not include herbal/other non‐homeopathic substances available over the counter such as Echinacea as this has already been reviewed (Linde 2006).
Types of outcome measures
Primary outcomes
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Cure: defined as the reduction or resolution of symptoms of ARTIs (fever/body temperature, cough, pain, malaise/feeling of illness, rhinorrhoea, etc) in the short term (up to 14 days) and long term (up to three months).
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Recurrence of ARTIs (time to recurrence included).
Secondary outcomes
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Duration of illness from time of randomisation until resolution of symptoms (measured longitudinally at intervals of weeks to months or years).
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Need for hospitalisation.
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Length of stay.
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Days off school and days off work for parents.
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Incidence of complications such as pneumonia, otitis media, meningitis, etc, in the short term (up to 14 days) and long term (up to three months).
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Any adverse events of homeopathic remedies.
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Quality of life.
Search methods for identification of studies
Electronic searches
We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, latest issue) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database (EED), MEDLINE (1966 to present), EMBASE (1990 to present), Cambase (1871 to present), Hominform (1951 to present) and International Clinical Trial Registry Platform (ICTRP) for published, unpublished and ongoing trials. We will not impose any language, publication year or publication status restrictions.
We will use the following search strategy to search MEDLINE and CENTRAL. We will combine the MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE (Lefebvre 2011). We will adapt the search strategy to search the other databases.
MEDLINE (Ovid)
1 exp Respiratory Tract Infections/
2 respiratory tract infection*.tw.
3 respiratory infection*.tw.
4 (urti or uri or lrti or lri or ari).tw.
5 Nasopharyngitis/
6 (nasopharyngit* or rhinopharyngit*).tw.
7 exp Sinusitis/
8 sinusit*.tw.
9 rhinitis/
10 rhinit*.tw.
11 rhinosinusit*.tw.
12 ((runny or running or blocked or congest* or discharg* or stuffed or stuffy) adj2 (nose* or nasal)).tw.
13 Sneezing/
14 sneez*.tw.
15 Pharyngitis/
16 pharyngit*.tw.
17 pharyngotonsillit*.tw.
18 sore throat*.tw.
19 Tonsillitis/
20 tonsillit*.tw.
21 exp Laryngitis/
22 laryngit*.tw.
23 croup*.tw.
24 tracheitis/
25 tracheit*.tw.
26 Epiglottitis/
27 epiglottit*.tw.
28 Common Cold/
29 common cold*.tw.
30 coryza.tw.
31 exp Otitis Media/
32 otitis media.tw.
33 (AOM or OME).tw.
34 Cough/
35 cough*.tw.
36 Influenza, Human/
37 (influenza* or flu).tw.
38 exp Bronchitis/
39 (bronchit* or bronchiolit*).tw.
40 exp Pneumonia/
41 pneumon*.tw.
42 or/1‐41
43 Homeopathy/
44 formularies, homeopathic/ or pharmacopoeias, homeopathic/
45 (homeopath* or homoeopath*).tw.
46 Complementary Therapies/
47 Holistic Health/
48 (pulsatilla or chamom* or sulphur or calcarea or drosera or tonsiotren or lomabronchin).tw,nm.
49 dilution*.tw.
50 or/43‐49
51 42 and 50
Searching other resources
We will scan reference lists of identified publications for additional trials and contact trial authors where necessary to retrieve other RCTs and systematic reviews relevant to this review. In addition, we will contact trial authors, manufacturers of homeopathic preparations and specialists in homeopathic research for published and unpublished studies. We will also search trial registers in order to identify ongoing and completed relevant trials.
Data collection and analysis
Selection of studies
Two review authors (JS, AM) will independently review titles and abstracts to select potentially eligible studies. The same two review authors (JS, AM) will independently conduct a full‐text analysis by assessing for compliance of studies with the eligibility criteria. We will resolve disagreements about inclusion of a study by discussion first. A third author (WC) will arbitrate if the disagreement is due to a difference in interpretation. We will categorise the study as one that is awaiting assessment if we cannot reach agreement until further information is obtained from the trial authors. We will record the presence and resolution of disagreements on an electronic form, with different ink colour for changes after consensus.
Data extraction and management
We will design a data extraction form. All authors will review the form, which will be pilot tested with a sample of studies, reviewed and edited again to produce a final copy. We will follow this by training in how to use the form and coding instructions for data collection. Two review authors (AM, JS), familiar with the data extraction form, will independently extract data from every included trial using the standardised, piloted data collection forms, to minimise errors and reduce potential bias.
We will include the following information on the data collection forms.
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Authors.
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Publication year.
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Name of journal.
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Participants (including total number, demographics, duration and characteristics of illness etc.).
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Study type and methods.
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Intervention (type, route and duration).
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Results (outcome measures, time points, effect, statistical significance and adverse effects).
Two review authors (AM, WC) will independently extract data from all the reports into a single data collection form for multiple reports of the same study.
Assessment of risk of bias in included studies
Two authors (JS, WC) will independently assess the risk of bias of each study using the Cochrane Collaboration's tool for assessing risk of bias (Higgins 2011a). They will present the information in the 'Risk of bias' table available in RevMan 2011 for inclusion in the Cochrane review.
The features of the risk of bias tool include:
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random sequence generation;
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allocation concealment;
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blinding of participants and personnel;
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blinding of outcome assessment;
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incomplete outcome data;
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selective outcome reporting; and
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other sources of bias
We will describe each of the above domains as reported in the trial and we will make a judgement of adequacy for each entry we make. We will express the judgements as either 'low risk', 'high risk' or 'unclear risk' of bias. We will resolve any disagreements about inclusion of a study by discussion and consensus first. A third review author (AM) will arbitrate if disagreement is due to difference in interpretation. We will contact trial authors to request information where clarification is required. We will report disagreements in the review if they remain unresolved.
Measures of treatment effect
We will express dichotomous data recording the primary outcome of cure and secondary outcomes of hospitalisation and presence of complications or adverse events as odds ratios (OR) with 95% confidence intervals (CIs). We will express outcomes measured as continuous data (e.g. for symptom scores) using the mean difference (MD) and the standardised mean difference (SMD) with standard deviations (SDs). We will calculate the absolute risk reduction (ARR) and numbers needed to treat for an additional beneficial outcome (NNTB) if the results are statistically significant.
Unit of analysis issues
The individual participant level will be the unit of analysis. We will adjust the outcomes for clustering based on the intra‐cluster correlation as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b) if the unit of analysis is not the same as the unit of randomisation, such as in cluster‐RCTs.
Dealing with missing data
We will contact trial authors to request information on missing data wherever possible and we will perform an intention‐to‐treat (ITT) analysis (assuming missing data as treatment failure) if results are unattainable. We will also strive to address the impact of missing data on the review in the Discussion section.
Assessment of heterogeneity
We will assess heterogeneity among trials in two ways. First, we will assess face value heterogeneity by comparing trial populations, settings and methods. Second, we will assess the presence of statistical heterogeneity by calculating the Chi2 test and I2 statistic (Higgins 2011b). We will use a cut‐off value of P < 0.10 to determine statistical significance of the Chi2 test. We will consider an I2 statistic > 50% as important heterogeneity. If heterogeneity is present, we will examine the methodological and clinical characteristics of the included trials to explore the possible causes. We will then conduct sensitivity analyses and to summarise our findings. We will produce a table to report findings and subsequently assess to see if there is any change in overall effect.
Assessment of reporting biases
We will attempt to construct funnel plots if more than 25 trials are available in order to assess the risk of publication bias. We will follow the recommendations on testing for funnel plot asymmetry as described in section 10.4 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c). We will explore the results in the Discussion section of this review if applicable.
Data synthesis
We will use RevMan 2011 to synthesise data. We will perform a fixed‐effect meta‐analysis in the absence of heterogeneity. We will not pool data but report the results of trials in a systematic review in the presence of clear face value heterogeneity. We will apply a random‐effects model (Higgins 2011b) where important statistical heterogeneity is detected (defined as above). We will pool all studies and perform sensitivity analysis to investigate which studies contribute to heterogeneity and discuss this in our discussion section.
Subgroup analysis and investigation of heterogeneity
We will perform a subgroup analysis to investigate the effect of homeopathic care and homeopathic remedies in different groups. We will report on the following subgroups. Where possible we will investigate the effect of homeopathic care compared with homeopathic remedies alone (i.e. not administered by a homeopath).
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Infants versus older children.
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Children under six years of age versus older children.
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Homeopathic care compared with placebo.
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Homeopathic care versus homeopathic remedies.
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Homeopathic remedies versus placebo.
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Homeopathic care compared with other active treatments.
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Homeopathic remedies compared with other active treatments.
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Homeopathic care compared with antibiotics.
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Homeopathic remedies compared with antibiotics.
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Children with co‐morbidities versus children with no co‐morbidities.
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URTI versus LRTI (if plausible).
Sensitivity analysis
We will perform a sensitivity analysis to explore the impact of risk of bias on the overall treatment effect. We will pool studies with a low risk of bias first and then add studies with a high risk of bias and assess which studies contribute to heterogeneity.
