Background
Methods
Search strategy, data sources and trial eligibility
Outcome definitions
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Mortality
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Morbidity
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○ Treatment failure
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○ Pathology; symptoms of disease
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Health impairment (loss/abnormality of function, incl. presence of pain)
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Limitation of activity (disability, incl. days off work/school because of ill health)
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Restriction of participation (quality of life)
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Surrogate outcome (e.g. blood test data, bone mineral density).
Data extraction
Assessment of risk of bias
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Rating A = Low risk of bias in all seven domains.
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Rating Bx = Uncertain risk of bias in x domains; low risk of bias in all other domains.
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Rating Cy.x = High risk of bias in y domains; uncertain risk of bias in x domains; low risk of bias in all other domains.
Designating an RCT as ‘reliable evidence’
Study selection for meta-analysis
Statistical analysis
Data preparation
Heterogeneity and publication bias
Sensitivity analysis
Sub-group analysis
Disease-specific treatment effect of non-individualised homeopathy
Results
Included studies
Characteristics of included studies
# | First author | Year | Category | Condition | Acute/ Chronic | Participants’ demographics | Study setting | Potency ≥12C | Hom. type | Funding source | Free of vested interest a
|
---|---|---|---|---|---|---|---|---|---|---|---|
A42 |
Aabel
| 2001 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Patients treated for hay fever due to birch pollen allergy | Specialist outpatient department in Norway | Y | Isopathy | Research Council of Norway. Homeopathic remedy and placebo tablets were gift from DCG, Gothenburg, Sweden | N |
A43 |
Aabel
| 2000 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Patients treated for hay fever due to birch pollen allergy | Specialist outpatient department in Norway | Y | Isopathy | Research Council of Norway. Homeopathic remedy and placebo tablets were gift from DCG, Gothenburg, Sweden | N |
A44 |
Aabel
| 2000 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Patients treated for hay fever due to birch pollen allergy | Specialist outpatient department in Norway | Y | Isopathy | Research Council of Norway. Homeopathic remedy and placebo tablets were gift from DCG, Gothenburg, Sweden | N |
A47 | Baker | 2003 | Mental Disorder | Anxiety | Acute | Anxious students, aged 18-60 years | University, Australia | N | Single | ‘Brauer Biotherapies Pty Ltd (Adelaide) manufactured the homeopathic preparation specifically for the study’ | U |
A48 | Balzarini | 2000 | Dermatology | Radiodermatitis | Acute | Patients with dermatitis caused by radiotherapy for breast cancer | Rehabilitation and palliative care department, Italy | Mixed | Combn. | None stated | U |
A49 | Beer | 1999 | Obstetrics and Gynaecology | Induction of labour | Acute | Women (at least 18 years old) between 38 and 42 weeks’ gestation and cervical dilation (≤3 cm) | Akademisches Lehrkrankenhaus der RWTH Aachen | N | Single | None stated | U |
A50 | Belon | 2006 | Toxicology | Arsenic toxicity | Chronic | People at high risk of arsenic contamination | Rural village, India | Y | Single | Hom pharm | N |
A51 |
Belon
| 2007 | Toxicology | Arsenic toxicity | Chronic | People at high risk of arsenic contamination | Rural village, India | Y | Single | Hom pharm | N |
A52 | Bergmann (a) | 2000 | Obstetrics and Gynaecology | Female infertility: oligomenorrhoea | Chronic | Women, age 18 - 40 | Universitäts-Frauenklinik Heidelberg | N | OTC complex | None stated | U |
A52 | Bergmann (b) | 2000 | Obstetrics and Gynaecology | Female infertility: amenorrhoea | Chronic | Women, age 18 - 40 | Universitäts-Frauenklinik Heidelberg | N | OTC complex | None stated | U |
A53 |
Bernstein
| 2006 | Dermatology | Psoriasis | Acute | Patients with psoriasis | Dermatology Centre in the USA | N | Single | “Supported in part” by Apollo Pharmaceuticals Inc., manufacturers of Reliéva | N |
A55 |
Berrebi
| 2001 | Obstetrics and Gynaecology | Postpartum lactation | Acute | Women immediately after childbirth and who did not wish to breast-feed | Childbirth unit, university hospital, Toulouse, France | N | Combn. | Hom pharm | N |
A56 | Bignamini | 1987 | Cardiovascular | Hypertension | Chronic | Elderly males or females with hypertension | Two old people’s homes, Italy | Y | Single | “We thank Laboratoires Boiron for material provided” | U |
A59 | Cialdella | 2001 | Mental Disorder | Withdrawal of benzodiazepines | Chronic | Men and women aged >18 years, taking BZD for >3 mo. | GP practices in France (multi-centre) | N | OTC complex b
| External (hom pharm / govt.) | N |
A60 | Clark | 2000 | Musculoskeletal | Plantar fasciitis | Acute | Patients treated with heel pain due to fasciitis | Podiatry clinic, England | Y | Single | None stated | U |
A272 | Colau | 2012 | Obstetrics and Gynaecology | Menopausal syndrome | Chronic | Women aged ≥50 years; experienced amenorrhea for >12 months; spontaneously complained of hot flashes that had started <2 years previously | 35 gynaecologist private practices in France | N | OTC complex | Hom pharm. | N |
A61 | Cornu | 2010 | Surgery and Anaesthesiology | Post-operative bleeding | Acute | Males or females, >18 years old, for whom elective aortic valve surgery planned | University hospital department, France | N | Combn. | Financially supported and assisted in design by Laboratoires Boiron, but ‘conducted in total independence’ | U |
A62 | Diefenbach | 1997 | Respiratory Infection | Bronchitis | Acute | Patients (M/F) with bronchitis | 4 doctors’ practices in Germany | N | OTC complex | None stated | U |
A63 | Ernst | 1990 | Cardiovascular | Varicose veins | Acute | Varicose veins in the legs | Rehabilitation clinic in Austria | N | OTC complex | None stated | U |
A64 | Ferley | 1989 | Respiratory Infection | Influenza | Acute | Age ≥12 years, flu-like symptoms, temp ≥38C | General practices in Rhône-Alpes region, France | Y |
aIsopathy | None stated | U |
A67 | Frass | 2005 | Respiratory Infection | Tracheal secretions | Acute | Patients with accumulation of heavy secretions in the trachea | Intensive Care Unit at a university hospital in Austria | Y | Single | None stated | U |
A68 | Freitas | 1995 | Allergy and Asthma | Childhood asthma | Chronic | Children aged 12 mo to 12 years, with a mild to severe asthma crisis in the previous 6 mo. | Outpatient clinic in São Paulo, Brazil | N | Single | None stated | U |
A69 |
Friese
| 2007 | Ear, Nose and Throat | Sinusitis | Acute | Patients from 18 - 65 (m/f) | 10 medical centres in Ukraine | N | OTC complex | None stated | U |
A70 | Friese | 1997 | Ear, Nose and Throat | Adenoid | Acute | Children (M/F) between age 4 and 10 | Universitäts Kinderklinik Tübingen | Mixed | Combn. | Remedies were gift from hom pharm. | N |
A74 | Gerhard (a) | 1998 | Obstetrics and Gynaecology | Female infertility: amenorrhoea | Chronic | Women with secondary amenorrhoea | University hospital, Germany | N | OTC complex | Direct support from the company that provided the homeopathic medicine for the trial (senior author is company employee) | N |
A74 | Gerhard (b) | 1998 | Obstetrics and Gynaecology | Female infertility: luteal insufficiency | Chronic | Women with luteal insufficiency | University hospital, Germany | N | OTC complex | Direct support from the company that provided the homeopathic medicine for the trial (senior author is company employee) | N |
A74 | Gerhard (c) | 1998 | Obstetrics and Gynaecology | Female infertility: idiopathic | Chronic | Women with idiopathic infertility | University hospital, Germany | N | OTC complex | Direct support from the company that provided the homeopathic medicine for the trial (senior author is company employee) | N |
A75 | GRECHO | 1989 | Surgery and Anaesthesiology | Post-operative ileus | Acute | Men and women aged >18 years, having one of several stated operations | 12 hospitals in France | Mixed | Combn. | Govt. | Y |
A274 |
Harrison
| 2013 | Mental Disorder | Insomnia | Chronic | Males aged 18-40, with chronic primary insomnia: at least 3 days per week for period of 1 mo to 10 years | University clinic | N | Combn. | University | Y |
A76 |
Hart
| 1997 | Surgery and Anaesthesiology | Post-operative pain | Acute | Patients with abdominal hysterectomy | Hospital, England | Y | Single | None stated | U |
A78 |
Hitzenberger
| 2005 | Cardiovascular | Hypertension | Chronic | Hypertensive patients (M/F) | Not explicitly mentioned | N | OTC complex | The study was funded, but it is not stated by whom | U |
A79 | Hofmeyr | 1990 | Obstetrics and Gynaecology | Postpartum pain | Acute | Postpartum women with episiotomy or perineal tearing requiring suture | University hospital, South Africa | N | Single b
| None stated | U |
A80 |
Jacobs
| 2006 | Gastroenterology | Childhood diarrhoea | Acute | Children with a history of acute diarrhoea | Two municipal clinics, Honduras | Y | Combn. | External (hom research foundation) | Y |
A81 | Jacobs | 2007 | Tropical Disease | Dengue fever symptoms | Acute | Patients over age 12 with a case definition of dengue | Two health centres, Honduras | Y | Combn. | External (hom research foundation); meds ‘furnished’ by hom pharm | U |
A83 | Kaziro | 1984 | Surgery and Anaesthesiology | Post-operative pain/swelling | Acute | Patients with extraction of impacted wisdom teeth | Dental hospital, England | Y | Single | None stated | U |
A84 | Khuda-Bukhsh | 2005 | Toxicology | Arsenic toxicity | Chronic | People at high risk of arsenic contamination | Rural village, India | Y | Single | Hom pharm. | N |
A85 | Khuda-Bukhsh | 2011 | Toxicology | Arsenic toxicity | Chronic | People at high risk of arsenic contamination | Rural village, India | Y | Single | Hom pharm. | N |
A86 | Kim | 2005 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Asthmatic people allergic to house dust mite | College of Naturopathic Medicine and Health Sciences, USA | N | Isopathy | Internal / External (hom pharm) | N |
A88 |
Kolia-Adam
| 2008 | Mental Disorder | Insomnia | Chronic | Males or females, 18-50 years, suffering from insomnia for > 1 year | University health clinic, South Africa | Y | Single | None stated | U |
A89 | Kotlus | 2010 | Surgery and Anaesthesiology | Post-operative bruising | Acute | Males undergoing upper blepharoplasty | University department of ophthalmology, USA | Y | Combn. | Supported in part by external foundation | Y |
A91 |
Labrecque
| 1992 | Dermatology | Warts | Chronic | Aged 6-59 years and at least 1 plantar wart untreated during previous 3 months | Hospital-based family medicine unit, Canada | Mixed | Combn. | Hospital pharmacy | Y |
A92 | Leaman | 1989 | Dermatology | Minor burns | Acute | Aged 15-60 years with minor burns within previous 6 h | Hospital Accident and Emergency Dept, England | Y | Single | None stated | U |
A93 | Lewith | 2002 | Allergy and Asthma | Allergic asthma | Chronic | Asthmatic people allergic to house dust mite | Hospital clinic, England | Y | Isopathy | Internal / External (charity) / Purchase from hom pharm | Y |
A94 | Lipman | 1999 | Miscellaneous | Snoring | Acute | People treated for snoring | ENT specialist clinic in the USA | N | OTC complex | None stated | U |
A293 | Malapane | 2014 | Ear, Nose and Throat | Tonsillitis | Acute | Children, aged 6-12 years, with acute viral tonsillitis | University department of homeopathy, South Africa | N | OTC complex | None stated | U |
A95 |
McCutcheon
| 1996 | Mental Disorder | Anxiety | Acute | Adults with above average anxiety | University, USA | N | OTC complex | Hom pharm | N |
A275 | Naidoo | 2013 | Allergy and Asthma | Allergic skin reaction | Acute | Males or females, aged 18 to 45; positive skin test; living with a cat for a period of ≥ 6 mo; suffering from allergy-like symptoms | University health training centre | N | Combn. | None stated | U |
A100 | Oberbaum | 2001 | Oral/Dental | Stomatitis | Acute | Cancer patients with stomatitis | Children’s Medical Centre in Israel | N | OTC complex | None stated | U |
A101 | Oberbaum | 2005 | Obstetrics and Gynaecology | Postpartum bleeding | Acute | Women after childbirth | Medical centre in Israel | Mixed | Combn. | Research foundation | Y |
A103 | Padilha | 2011 | Toxicology | Lead poisoning | Acute | Workers at risk of lead contamination | Clinic of battery plant, Brazil | Y | Single | Explicitly no funding source | Y |
A104 | Papp | 1998 | Respiratory Infection | Influenza | Acute | Age 12-60 years, specified flu-like symptoms, onset within last 24 h, temp ≥38C | General or specialist medical practices, Germany | Y |
a Isopathy | None stated | U |
A105 | Paris | 2008 | Surgery and Anaesthesiology | Post-operative analgesic intake | Acute | Male or female, aged 18-60 years, undergoing surgery of anterior cruciate ligamen | University hospital, France | N | Combn. | Hom pharm | N |
A108 | Rahlfs | 1976 | Gastroenterology | Irritable bowel syndrome | Acute | Patients, male or female, aged 20-60, with diagnosis of irritable bowel syndrome | 12 general medical practices in Germany | N | Single b
| None stated | U |
A109 | Rahlfs | 1978 | Gastroenterology | Irritable bowel syndrome | Acute | Patients, male or female, aged 20-60, with diagnosis of irritable bowel syndrome | 39 general medical practices in Germany | N | Single | External (hom research foundation) | Y |
A277 |
Razlog
| 2012 | Mental Disorder | ADHD | Chronic | School children, aged 5-11, diagnosed with ADHD | Primary schools in South Africa | N | Single | University | Y |
A111 | Reilly | 1986 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Patients aged over 5 with at least a 2-year history of seasonal rhinitis and current symptoms of grass pollen allergy | Two hospital clinics and 26 NHS general practitioners in the UK | Y | Isopathy | External: charity; govt. | Y |
A112 | Reilly | 1994 | Allergy and Asthma | Allergic asthma | Chronic | Patients aged over 16 with at least a 1-year history of asthma and reactive to inhaled allergens | Asthma outpatient clinic, Scotland | Y | Isopathy | External / purchase from hom pharm | Y |
A113 | Robertson | 2007 | Surgery and Anaesthesiology | Post-operative pain | Acute | Patients over the age of 18 undergoing tonsillectomy | Hospital, England | Y | Single | Internal / External (hom pharm) | N |
A116 |
Schmidt
| 2002 | Miscellaneous | Those benefited by reduced body weight | Acute | Fasting patients encountering static or increased body weight | Hospital for internal and complementary medicine, Germany | Y | Single | “The foundation of the Krankenhaus für Naturheilweisen funded the study, paying salaries or fees to contributors and collaborators.” | U |
A117 |
Seeley
| 2006 | Surgery and Anaesthesiology | Post-operative bruising | Acute | Female patients undergoing elective rhytidectomy | Hospital, Canada | Unknown | Single | Hom pharm. | N |
A278 |
Sencer
| 2012 | Oral/Dental | Mucositis | Acute | Patients aged 3-25 years, undergoing myeloablative haematopoietic SCT for malignant and non-malignant conditions | Oncology centres in USA, Canada and Israel | N | OTC complex | Government (NIH) grant | Y |
A120 | Singer | 2010 | Surgery and Anaesthesiology | Post-operative pain | Acute | Patients (M/F) age > = 18 | 2 centres | N | OTC complex | Financial support by producing company which ‘supplied the study medication’ but, by contractual agreement, had ‘no control over the flow of the study, the data analysis, or the decision when and where to publish the study findings’ | Y |
A122 |
Stevinson
| 2003 | Surgery and Anaesthesiology | Post-operative pain/swelling | Acute | Aged 18–70 years undergoing elective hand surgery for carpal tunnel syndrome | Hospital, England | Y / N | Single b
| Hom. research foundation / drugs ‘supplied by’ hom pharm | U |
A123 | Taylor | 2000 | Allergy and Asthma | Perennial allergic rhinitis | Chronic | Patients with allergy to house dust mites, animals, pollens or foods | Specialist outpatient department in the UK | Y | Isopathy | External (hom and non-hom charities) | Y |
A125 | Tveiten | 1991 | Musculoskeletal | Muscle soreness | Acute | Male marathon runners, Norway | City of Oslo | Y | Single | None stated | U |
A126 | Tveiten | 1998 | Musculoskeletal | Muscle soreness | Acute | Marathon runners, Norway | City of Oslo | Y | Single | Research Council of Norway. Homeopathic remedy and placebo tablets were gift from hom pharm. | N |
A128 | Vickers | 1998 | Musculoskeletal | Muscle soreness | Acute | Long-distance runners, aged 18 or over, England | London community | Y | Single | Charity / drugs gifted by hom pharm | N |
A130 |
Weiser
| 1994 | Ear, Nose and Throat | Sinusitis | Chronic | Patients (M/F) with chronic sinusitis | 11 ENT doctors’ practices in Germany | N | OTC complex b
| None stated | U |
A131 | Wiesenauer | 1985 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Patients treated for hay fever | Doctors’ practices in Germany | N | Single | External (hom pharm) | N |
A132 |
Wiesenauer
| 1989 | Ear, Nose and Throat | Sinusitis | Acute | Patients (M/F) with acute or chronic sinusitis | 47 doctors’ practices | N | Combn. c
| Funded by two foundations | Y |
A133 | Wiesenauer | 1990 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | M/F, all ages | 54 doctors’ practices | N | Single | Funded by two foundations | Y |
A134 | Wiesenauer | 1991 | Rheumatology | Rheumatoid arthritis | Chronic | Patients (m/f), age 18 - 70, with chronic polyarthritis | 6 doctors’ practices | N | OTC complex | None stated | U |
A135 | Wiesenauer | 1995 | Allergy and Asthma | Seasonal allergic rhinitis | Acute | Patients treated for hay fever | Doctors’ practices in Germany | N | Single | None stated | U |
A136 | Wolf | 2003 | Surgery and Anaesthesiology | Post-operative pain | Acute | Age 10 - 65 (M/F), varicose veins | Gefäßchirurgische Klinik in Berlin-Buch | N | Single | Remedies were gift from hom pharm. | N |
A137 | Zabolotnyi | 2007 | Ear, Nose and Throat | Sinusitis | Acute | Patients, aged 18-60 years, treated for acute maxillary sinusitis, with at least 8 d of symptoms | ENT specialist clinics, Ukraine | N | OTC complex | None stated | U |
Summary of findings
# | First author | Year | Pilot | Power calc. | ITT sample | PP sample | PP sample > median (62.5) | Attrition rate % | Original ITT analysis | ‘Main’ outcome identified | Nature of ‘main’ outcome | End-point |
---|---|---|---|---|---|---|---|---|---|---|---|---|
A42 |
Aabel
| 2001 | N | N | 51 | 51 | N | 0.0 | N | Daily symptom score (VAS) | Continuous | 10 days |
A43 |
Aabel
| 2000 | N | Y | 70 | 66 | Y | 5.7 | N | Daily symptom score | Continuous | 32 days |
A44 |
Aabel
| 2000 | N | Y | 80 | 73 | Y | 8.8 | N | Daily symptom score (VAS) | Continuous | 10 days |
A47 | Baker | 2003 | N | Y | ? | 44 | N | ? | N | Revised Test Anxiety (RTA) scale | Continuous | 4 days |
A48 |
bBalzarini | 2000 | N | N | 66 | 61 | N | 7.6 | N | Index of Total Severity during Recovery (re: skin colour, temp, oedema, pigmentation) | Continuous | 7–8 weeks |
A49 |
bBeer | 1999 | N | N | 40 | 40 | N | 0.0 | Y | Time between to regular uterine contractions | Continuous | 7 h or induction of labour |
A50 | Belon | 2006 | N | N | 43 | 43 | N | 0.0 | N | Reversal in expression of antinuclear antibody titre | Dichotomous | 1 month |
A51 |
Belon
| 2007 | Y | N | 39 | 25 | N | 35.9 | N | Blood arsenic concentration | Continuous | 2 months |
A52 |
bBergmann (a) | 2000 | N | Y | ? | 37 | N | ? | N | Cycle normalisation | Dichotomous | 3 months or 3 cycles |
A52 |
bBergmann (b) | 2000 | N | Y | ? | 30 | N | ? | Y | Cycle normalisation | Dichotomous | 3 months or 3 cycles |
A53 |
Bernstein
| 2006 | N | N | 200 | 171 | Y | 14.5 | N | Psoriasis Area Severity Index | Continuous | 12 weeks |
A55 |
Berrebi
| 2001 | N | N | 71 | 71 | Y | 0.0 | N | Mammary pain (VAS) | Continuous | 4 days |
A56 | Bignamini | 1987 | N | N | 34 | 32 | N | 5.9 | N | (Systolic) Blood pressure | Continuous | 4 weeks |
A59 |
bCialdella | 2001 | N | Y | 96 | 61 | N | 36.5 | Y | “Success rate” for clinical global impression | Dichotomous | 30 days |
A60 | Clark | 2000 | Y | N | 18 | 14 | N | 22.2 | N | Daily pain (100 mm VAS) | Continuous | 14 days |
A272 | Colau | 2012 | N | Y | 108 | 101 | Y | 6.5 | Y | Hot flash score | Continuous | 12 weeks |
A61 | Cornu | 2010 | Y | Y | 92 | 92 | Y | 0.0 | Y | Cumulated blood loss at drain removal | Continuous | Up to 7 d |
A62 |
bDiefenbach | 1997 | N | N | 258 | 209 | Y | 19.0 | Y | Treatment success (‘very good’ + ‘good’ results) – physician-assessed | Dichotomous | Up to 3 weeks |
A63 |
bErnst | 1990 | N | N | 122 a
| 122 a
| N | 0.0 | N | Venous filling time | Continuous | 24 days |
A64 |
bFerley | 1989 | N | N | 478 | 462 | Y | 3.3 | N | Proportion of patients recovered (from 5 cardinal symptoms and from temp > 37.5) | Dichotomous | By 48 h |
A67 | Frass | 2005 | N | N | 55 | 50 | N | 9.1 | N | Total volume of tracheal secretions per day | Continuous | 2 days |
A68 |
bFreitas | 1995 | N | N | 86 | 69 | Y | 19.8 | N | Score of intensity, frequency and duration of symptoms | Continuous | 6 months |
A69 |
Friese
| 2007 | N | N | 144 | 68 | Y | 52.8 | Y | Sinusitis symptoms score | Continuous | 21 days |
A70 |
bFriese | 1997 | N | Y | 97 | 82 | Y | 15.5 | N | Frequency of non-adenoidectomy (imputed) | Dichotomous | 3 months |
A74 | Gerhard (a) | 1998 | N | Y | 38 | 28 | N | 26.3 | N | Frequency of pregnancy | Dichotomous | 3 months |
A74 | Gerhard (b) | 1998 | N | Y | 27 | 21 | N | 22.2 | N | Frequency of pregnancy | Dichotomous | 3 months |
A74 | Gerhard (c) | 1998 | N | Y | 31 | 17 | N | 45.2 | N | Frequency of pregnancy | Dichotomous | 3 months |
A75 | GRECHO | 1989 | N | Y | 300 | 300 | Y | 0.0 | N | Number of hours from operation until first stool | Continuous | Up to c.100 h |
A274 |
Harrison
| 2013 | Y | N | 34 | 28 | N | 17.6 | N | Sleep onset latency | Continuous | 28 days |
A76 |
Hart
| 1997 | N | N | 93 | 73 | Y | 21.5 | N | Frequency of improved pain score (VAS) | Dichotomous | Duration of 5 days |
A78 |
Hitzenberger
| 2005 | N | Y | ? | ? | - | ? | N | Blood pressure | Continuous | 6 weeks |
A79 |
bHofmeyr | 1990 | Y | N | 162 | 161 | Y | 0.6 | N | Daily questionnaire responses: those without moderate/severe perineal pain | Dichotomous | 4 days |
A80 |
Jacobs
| 2006 | N | N | 292 | 265 | Y | 9.2 | Y | Duration of diarrhoea | Continuous | Up to 7 days |
A81 | Jacobs | 2007 | Y | N | 60 | 58 | N | 1.7 | N | No. of days until no pain or fever for at least two consecutive days | Continuous | Up to 1 weeks |
A83 |
bKaziro | 1984 | N | N | 77 | 77 | Y | 0.0 | N | Pain score (VAS): Numbers without moderate/severe pain (imputed) | Dichotomous | 8 days |
A84 | Khuda-Bukhsh | 2005 | Y | N | 55 | 55 | N | 0.0 | N | Urine arsenic concentration (imputed) | Continuous | 11 days |
A85 | Khuda-Bukhsh | 2011 | Y | N | 28 | 14 | N | 50.0 | N | Urine arsenic concentration | Continuous | 2 months |
A86 | Kim | 2005 | Y | Y | 40 | 34 | N | 15.0 | Y | Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ total symptoms) | Continuous | 4 weeks |
A88 |
Kolia-Adam
| 2008 | N | N | 30 | 30 | N | 0.0 | N | Hours of sleep per night | Continuous | 8 weeks |
A89 | Kotlus | 2010 | N | N | 60 | 57 | N | 5.0 | N | Area of ecchymosis | Continuous | 7 days |
A91 |
Labrecque
| 1992 | N | Y | 174 | 162 | Y | 6.9 | N | Proportion of pts with healed warts (physician assessment) | Dichotomous | 18 weeks |
A92 |
bLeaman | 1989 | N | N | 34 | 34 | N | 0.0 | N | Pain (0-10 VAS) - area-under-the-curve | Continuous | 6 h |
A93 | Lewith | 2002 | N | N | 242 | 202 | Y | 16.5 | Y | Asthma VAS (imputed) | Continuous | 16 weeks |
A94 | Lipman | 1999 | N | N | 101 | 90 | Y | 10.9 | N | Average snoring score computed from responses to Snore Diary over last 5 nights of 10 | Continuous | Duration of 10 days |
A293 | Malapane | 2014 | Y | N | 30 | 30 | N | 0.0 | N | Tonsillitis pain score (Wong-Baker FACES) | Continuous | 6 days |
A95 |
McCutcheon
| 1996 | N | N | 77 | 58 | N | 24.7 | N | State Anxiety score | Continuous | Duration of 15 days |
A275 | Naidoo | 2013 | Y | N | 30 | 30 | N | 0.0 | N | Wheal diameter | Continuous | 4 weeks |
A100 | Oberbaum | 2001 | N | N | 32 | 30 | N | 6.3 | Y | Area-under-the-curve score for stomatitis symptoms (severity and duration) (imputed) | Continuous | 14 days minimum |
A101 |
bOberbaum | 2005 | Y | N | 45 | 40 | N | 11.1 | Y | Venous haemoglobin | Continuous | 72 h postpartum |
A103 | Padilha | 2011 | N | N | 131 | 120 | Y | 8.4 | Y | Proportion of workers with Pb decrease of at least 25% (imputed) | Dichotomous | 30 days |
A104 |
bPapp | 1998 | N | N | 372 | 334 | Y | 10.2 | N | Proportion of patients with physician-assessed recovery in health (i.e. ‘no symptoms’) | Dichotomous | By 48 h |
A105 | Paris | 2008 | N | Y | 131 | 105 | Y | 19.8 | Y | Proportion patients with cumulated consumption of morphine < 10 mg/day (imputed) | Dichotomous | 24 h post-op |
A108 |
bRahlfs | 1976 | Y | Y | ? | 63 | Y | ? | N | Improvement of irritable bowel syndrome (scale 1 + 2) | Dichotomous | 14 days |
A109 |
bRahlfs | 1978 | Y | N | 119 | 85 | Y | 28.6 | N | Improvement of irritable bowel syndrome (scale 3 + 4) | Dichotomous | 15 days |
A277 |
Razlog
| 2012 | Y | N | 20 | 18 | N | 10.0 | N | Conner’s PSQ (‘Impulsivity and/or hyperactivity’ category) | Continuous | 3 weeks |
A111 |
bReilly | 1986 | N | Y | 158 | 109 | Y | 31.6 | N | Propn. with improvement in daily overall VAS score (imputed) | Dichotomous | 5 weeks |
A112 |
bReilly | 1994 | N | Y | 28 | 24 | N | 14.3 | Y | Propn. with improvement in daily overall VAS score | Dichotomous | 4 weeks |
A113 | Robertson | 2007 | N | Y | 190 | 111 | Y | 41.6 | N | Tonsillectomy pain (VAS) score | Continuous | 14 days |
A116 |
Schmidt
| 2002 | N | Y | 208 | 194 | Y | 6.7 | Y | Reduction of body weight | Continuous | 3 days |
A117 |
Seeley
| 2006 | N | N | 29 | 26 | N | 10.3 | N | Area of ecchymosis | Continuous | 10 days |
A278 |
Sencer
| 2012 | N | Y | 195 | 106 | Y | 45.6 | N | Sum of Walsh scores for mucositis | Continuous | Up to 20 days post-transplant |
A120 | Singer | 2010 | N | Y | 80 | 79 | Y | 1.3 | Y | Area-under-the-curve pain score | Continuous | 14 days |
A122 |
Stevinson
| 2003 | Y | N | 64 | 62 | N | 3.1 | Y | Pain (Short Form McGill Pain Questionnaire | Continuous | 14 days |
A123 |
bTaylor | 2000 | N | Y | 51 | 50 | N | 2.0 | Y | Daily overall VAS score (imputed) | Continuous | 3–4 weeks |
A125 | Tveiten | 1991 | N | N | 44 | 36 | N | 18.2 | N | Muscle soreness (VAS) (imputed) | Continuous | 3 days |
A126 |
bTveiten | 1998 | N | N | ? | 46 | N | ? | N | Muscle soreness (VAS) | Continuous | 3 days |
A128 |
bVickers | 1998 | N | Y | ? | 400 | Y | ? | Y | Muscle soreness (VAS) | Continuous | 2 days |
A130 |
Weiser
| 1994 | N | Y | 173 | 155 | Y | 10.4 | N | Sinusitis score | Continuous | 5 months or on relapse |
A131 |
bWiesenauer | 1985 | N | N | 106 | 74 | Y | 30.2 | N | Symptom relief (nasal): ‘Symptom-free’ + ‘Obvious relief’ | Dichotomous | 4 weeks |
A132 |
Wiesenauer
| 1989 | N | N | 221 | 152 | Y | 31.2 | N | Sinusitis score | Continuous | 3–4 weeks |
A133 |
bWiesenauer | 1990 | N | N | 243 | 171 | Y | 29.6 | N | Symptom relief (nasal): ‘Symptom-free’ + ‘Obvious relief’ | Dichotomous | Approx 5 weeks |
A134 | Wiesenauer | 1991 | N | N | 176 | 106 | Y | 39.8 | N | Treatment success | Dichotomous | 12 weeks |
A135 |
bWiesenauer | 1995 | N | N | 132 | 120 | Y | 9.1 | N | Symptom relief (nasal): ‘Symptom-free’ + ‘Obvious relief’ | Dichotomous | 4 weeks |
A136 | Wolf | 2003 | Y | N | 60 | 59 | N | 1.7 | N | Haematoma area | Continuous | 2 weeks |
A137 | Zabolotnyi | 2007 | N | Y | 113 | 113 | Y | 5.3 | Y | Sinusitis severity score cf. Day 0 (imputed) | Continuous | 7 days |
Risk of bias and reliable evidence
Risk-of-bias domain | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
# | First author | Year | I | II | IIIa | IIIb | IV | V c
| VI | Risk of bias | Risk-of-bias rating |
(a) Included in meta-analysis
| |||||||||||
A272 | Colau | 2012 | Y | Y | Y | Y | Y | Y | Y | Low a
| A |
A103 | Padilha | 2011 | Y | Y | Y | Y | Y | Y | Y | Low a
| A |
A120 | Singer | 2010 | Y | Y | Y | Y | Y | Y | U | Uncertain a
| B1* |
A123 | Taylor | 2000 | Y | U | Y | Y | Y | Y | Y | Uncertain | B1 |
A47 | Baker | 2003 | Y | Y | Y | Y | U | Y | U | Uncertain | B2 |
A61 | Cornu | 2010 | Y | Y | U | U | Y | Y | Y | Uncertain | B2 |
A67 | Frass | 2005 | U | U | Y | Y | Y | Y | Y | Uncertain | B2 |
A93 | Lewith | 2002 | U | U | Y | Y | Y | Y | Y | Uncertain | B2 |
A275 | Naidoo | 2013 | U | U | Y | Y | Y | Y | Y | Uncertain | B2 |
A105 | Paris | 2008 | U | Y | Y | Y | U | Y | Y | Uncertain | B2 |
A126 | Tveiten | 1998 | Y | U | Y | Y | U | Y | Y | Uncertain | B2 |
A128 | Vickers | 1998 | Y | Y | Y | Y | U | Y | U | Uncertain | B2 |
A137 | Zabolotnyi | 2007 | Y | U | Y | Y | Y | U | Y | Uncertain | B2 |
A100 | Oberbaum | 2001 | U | U | Y | Y | Y | Y | U | Uncertain | B3 |
A62 | Diefenbach | 1997 | U | U | Y | U | U | Y | Y | Uncertain | B4 |
A64 | Ferley | 1989 | U | U | Y | U | Y | U | Y | Uncertain | B4 |
A79 | Hofmeyr | 1990 | Y | U | U | U | Y | U | Y | Uncertain | B4 |
A92 | Leaman | 1989 | U | U | Y | Y | U | Y | U | Uncertain | B4 |
A293 | Malapane | 2014 | U | U | U | U | Y | Y | Y | Uncertain | B4 |
A125 | Tveiten | 1991 | U | U | Y | U | U | Y | Y | Uncertain | B4 |
A135 | Wiesenauer | 1995 | U | U | Y | Y | U | Y | U | Uncertain | B4 |
A112 | Reilly | 1994 | U | U | U | U | Y | Y | U | Uncertain | B5 |
A48 | Balzarini | 2000 | U | U | U | U | U | Y | U | Uncertain | B6 |
A75 | GRECHO | 1989 | U | U | U | U | U | Y | U | Uncertain | B6 |
A83 | Kaziro | 1984 | U | U | U | U | U | Y | U | Uncertain | B6 |
A104 | Papp | 1998 | U | U | Y | U | U | U | U | Uncertain | B6 |
A81 | Jacobs | 2007 | Y | Y | Y | Y | Y | Y | N | High | C1.0 |
A131 | Wiesenauer | 1985 | Y | U | Y | Y | N | Y | Y | High | C1.1 |
A68 | Freitas | 1995 | Y | U | Y | Y | N | Y | U | High | C1.2 |
A111 | Reilly | 1986 | U | U | Y | Y | N | Y | Y | High | C1.2 |
A113 | Robertson | 2007 | Y | U | Y | Y | N | Y | U | High | C1.2 |
A133 | Wiesenauer | 1990 | U | U | Y | Y | N | Y | Y | High | C1.2 |
A86 | Kim | 2005 | Y | U | U | U | N | Y | Y | High | C1.3 |
A134 | Wiesenauer | 1991 | U | U | Y | U | N | Y | Y | High | C1.3 |
A59 | Cialdella | 2001 | U | U | U | U | N | Y | Y | High | C1.4 |
A63 | Ernst | 1990 | U | U | U | U | Y | Y | N | High | C1.4 |
A56 | Bignamini | 1987 | U | U | U | U | U | Y | N | High | C1.5 |
A84 | Khuda-Bukhsh | 2005 | U | U | U | U | U | U | N | High | C1.6 |
A94 | Lipman | 1999 | U | Y | Y | Y | N | N | Y | High | C2.1 |
A108 | Rahlfs | 1976 | N | N | Y | Y | U | Y | Y | High | C2.1 |
A70 | Friese | 1997 | U | U | Y | Y | N | N | Y | High | C2.2 |
A74 | Gerhard (a) | 1998 | Y | U | Y | U | N | Y | N | High | C2.2 |
A74 | Gerhard (b) | 1998 | Y | U | Y | U | N | Y | N | High | C2.2 |
A74 | Gerhard (c) | 1998 | Y | U | Y | U | N | Y | N | High | C2.2 |
A89 | Kotlus | 2010 | N | N | U | U | Y | Y | Y | High | C2.2 |
A50 | Belon | 2006 | N | N | U | U | Y | Y | U | High | C2.3 |
A136 | Wolf | 2003 | Y | U | U | U | Y | N | N | High | C2.3 |
A49 | Beer | 1999 | U | U | U | U | Y | N | N | High | C2.4 |
A52 | Bergmann (a) | 2000 | U | U | Y | U | U | N | N | High | C2.4 |
A52 | Bergmann (b) | 2000 | U | U | Y | U | U | N | N | High | C2.4 |
A101 | Oberbaum | 2005 | U | U | U | U | U | N | N | High | C2.5 |
A60 | Clark | 2000 | U | U | U | U | N | N | N | High | C3.4 |
A85 | Khuda-Bukhsh | 2011 | N | N | Y | Y | N | N | N | High | C5.0 |
A109 | Rahlfs | 1978 | N | N | N d
| N | N | Y | Y | High | C5.0 |
(b) Not included in meta-analysis
| |||||||||||
A80 | Jacobs | 2006 | Y | Y | Y | Y | Y | N b
| Y | High f
| C1.0 |
A91 | Labrecque | 1992 | Y | U | Y | Y | U | N b
| Y | High e
| C1.2 |
A274 | Harrison | 2013 | Y | U | Y | Y | U | N b
| U | High e
| C1.3 |
A78 | Hitzenberger | 2005 | U | U | Y | U | U | N b
| Y | High e
| C1.4 |
A277 | Razlog | 2012 | U | U | Y | Y | U | N b
| U | High e
| C1.4 |
A117 | Seeley | 2006 | U | U | U | U | Y | N b
| U | High e
| C1.5 |
A55 | Berrebi | 2001 | U | U | U | U | U | N b
| U | High e
| C1.6 |
A76 | Hart | 1997 | Y | Y | Y | Y | U | N | Y | High | C1.1 |
A116 | Schmidt | 2002 | Y | Y | Y | Y | Y | N b
| N | High | C2.0 |
A122 | Stevinson | 2003 | Y | Y | Y | Y | Y | N b
| N | High | C2.0 |
A278 | Sencer | 2012 | U | Y | Y | Y | N | N b
| Y | High | C2.1 |
A130 | Weiser | 1994 | Y | U | Y | Y | N | N | Y | High | C2.1 |
A43 | Aabel | 2000 | U | U | Y | Y | Y | N b
| N | High | C2.2 |
A44 | Aabel | 2000 | U | U | Y | Y | N | N b
| U | High | C2.2 |
A42 | Aabel | 2001 | U | U | U | Y | Y | N b
| N | High | C2.3 |
A132 | Wiesenauer | 1989 | U | U | Y | U | N | N | Y | High | C2.3 |
A53 | Bernstein | 2006 | U | U | U | U | U | N b
| N | High | C2.5 |
A69 | Friese | 2007 | U | U | U | U | N | N | N | High | C3.4 |
A88 | Kolia-Adam | 2008 | N | U | U | U | U | N | N | High | C3.4 |
A95 | McCutcheon | 1996 | U | U | U | U | N | N b
| N | High | C3.4 |
A51 | Belon | 2007 | N | N | N d
| N | N | N b
| U | High | C6.1 |
Meta-analysis
Heterogeneity and publication bias
Risk of bias and reliable evidence
-
High risk of bias/non-reliable evidence (‘C’-rated: N = 28): SMD = –0.38 (95% CI –0.50, –0.26; p < 0.001);
-
Uncertain risk of bias/non-reliable evidence (‘B’-rated: N = 23): SMD = –0.31 (95% CI –0.51, –0.11; p = 0.002);
-
Minimal or low risk of bias/reliable evidence (‘B1*’ plus ‘A’-rated: N = 3): SMD = –0.18 (95% CI –0.46, 0.09; p = 0.165).