GENERAL PRACTICE Systematic review ofclinical efficacy oftopical treatments for head lice Robert H Vander Stichele, Els M Dezeure, Marc G Bogaert Abstract capitis) in which the outcome was measured clinically Objectives-To collect and evaluate all trials on by inspection of the scalp to determine cure rate clinical efficacy oftopical treatments for head lice. (absence oflive lice and viable nits). Design-Systematic review of randomised trials identified from following data sources: Medline, SEARCH STRATEGY International Pharmaceutical Abstracts, Science We searched the medical literature in Medline (1966 Citation Index, letters to key authors and companies, to March 1995 using the MESH keywords "Pedicu- and hand search ofjournals. losis," "Lice," "Pediculus"), in International Pharma- Setting-Trials in schools or communities. ceutical Abstracts, and in the Science Citation Index Subjects-Patients infested with lice. without restriction for language of publication. We Main outcome measure-Cure rate (absence of scanned the references of all identified clinical trials. live lice and viable nits) on day 14 after treatment. We sent letters requesting information about Results-Total of 28 trials were identified and unpublished studies to seven key authors in the evaluated according to eight general and 18 lice subject, to the pharmaceutical companies active in this specific criteria. Of the 14 trials rated as having low subject, and to the World Health Organisation centre to moderate risk ofbias, seven were selected as they Vector Biology Control. We hand searched journals used the main outcome measure. These seven trials in which key references were published for comments, described 21 evaluations of eight different com- letters, or corrections in the year after publication of pounds and placebo (all but two evaluations were of the key reference. single applications). Only permethrin 1% creme rinse showed efficacy in more than two studies with REVIEW the lower 95% confidence limit of cure rate above We focused on clinical efficacy-the result of 90%. pediculicidity, ovicidity, and residual activity-and so Conclusions-Only for permethrin has sufficient we chose cure rate as the main outcome measure for evidence been published to show efficacy. Less clinical evaluation. The cure rate is the percentage expensive treatments such as malathion and carbaryl of patients cured after application of the treatment need more evidence of efficacy. Lindane and the (the 95% confidence interval=p. 1-96 N/p (100-p)/n, natural pyrethrines are not sufficientiy effective to where p is the sample percentage and n the number of justify their use. subjects in the study). Determination of the cure rate by experienced evaluators-on the basis of visual inspection for viable nymphs in nits, hatching nymphs, Introduction and adult lice (with a x 10 magnifying lens)-has an Head lice are among the most common of human acceptable specificity and sensitivity.9 We considered ectoparasites, though they are not vectors of serious an interval of 14 days between treatment and evalu- diseases and in many cases do not cause symptoms.'` ation to be optimal as this would allow evaluation ofthe Treatment with natural pyrethrines has been known combined effect of pediculicidity (on living lice), for more than 100 years, and lindane has been used ovicidity (on ripening eggs), and residual activity (on since the second world war. The synthetic pyrethrines hatching nymphs and reinfesting lice). were marketed in the 1950s, malathion and carbaryl in We evaluated all identified clinical trials with regard the '60s, and permethrin in the '80s. Although to eight general criteria of quality in clinical trials products abound, the prevalence of head lice remains (adapted from Chalmers et aPl) and 18 criteria specific high and epidemics occur regularly despite all efforts at for head lice treatment (see table I). We developed control.'5 Problems such as fear of insects (ento- these specific criteria after studying the literature to Heymans Institute of mophobia), fear of stigmatisation, and denial of systematically screen the trials for flaws in design, Pharmacology, University infection by patients and schools may cause under- execution, or reporting. Firstly, we made a structured ofGhent, De Pintelaan, treatnent, overtreatment, and unnecessary pro- abstract of each clinical trial according to recom- 185, B-9000 Ghent, phylaxis, which can lead to development of resistance mended guidelines." Each of us then independently Belgium and insufficient control of assessed the trials. Trials were rejected if four or more Robert H Vander Stichele, epidemics.6 Furthermore, flaws in general criteria or 12 or more flaws in treatment generalpractitioner many of the commercially available treatments might be underdosed, incorrectly labelled, or ineffective. specific criteria were found. The remaining trials were Els M Dezeure, school health rated as having a low risk of bias if less than servicesphysician Our aim was to collect and evaluate all trials of eight Marc G Bogaert, clinical clinical efficacy oftopical treatments for head lice.78 specific criteria were flagged, or a moderate risk of bias pharmacologist if otherwise. Again, we set these cut off points for rating of quality after studying the literature. The Correspondence to: structured abstracts, assessment scores, and overall Dr Vander Stichele. Methods ratings were submitted to an advisory panel (four We searched for trials of topical treaunents for physicians and a community pharmacist) and BMg 1995;311:604-8 people infested with head lice (Pediculus humanus discussed until consensus was reached. Of the trials of 604 BMJ VOLUME 311 2 SEPTEMBER 1995 TABLE i-Criteria of quality in evaluation of design, execution, and As we decided not to accept the company's demands reporting oftrials on clinical efficacy oftopical treatmentfor head lice for confidentiality, the full texts of these studies were Item No Criterion not made available to us and these trials were not included in the analysis. Hand searching did not reveal General additional relevant reports of trials. The search in the 1 Randomisation procedure 2 Concealment ofallocation to patients Science Citation Index showed only limited citing 3 Concealment of allocation to investigators activity in this field. An official ofWHO confirmed that 4 Precision ofdefinition ofexclusion criteria the debate on the choice of head lice treatment 5 Handling and reporting ofdrop outs for the 6 Ethical procedures* list of essential drugs had been based on expert opinion 7 Statistical procedures without a formal literature review. Narrative reports of 8 Appropriateness ofconclusions studies and older reports of treatment campaigns4145 Treatment specific were not included in the analysis. 1 Documentation ofprior exposure ofscreened population to pesticides (therapeutic or agricultural) Four studies were not controlled,12 18 26 39 three 2 Documentation ofhistory ofprevious lice treatment and studies (two of malathion and one of permethrin) were comorbidity ofindex patients 3 Quality ofinformed consent procedure (involvement ofparents) placebo controlled,'52' 23 and the remaining 21 studies 4 Inclusion criteria (definition of "current" head lice infection) were comparisons between two or more active sub- 5 Specification ofthe formulation of active ingredients stances. We rated the quality of the identified trials 6 Storage and manipulation ofpharmaceutical compound 7 Time and season of study according to the criteria in table I and rejected 14 ofthe 8 Prevalence oflice in study area trials because of an excess of general or treatment 9 Standardisation ofcotreatment and swimming 10 Identity ofapplicants and evaluators specific flaws (table II). Seven trials were excluded 11 Application procedure from the analysis, although their methodological 12 Intensity oftracing contacts 13 Use ofnit combs quality was acceptable, because the cure rate was not 14 Documentation of pediculicidity determined on day 14 after treatment (three measured 15 Documentation ofovicidity cure rate on 521 38 and four measured it on 21 16 Documentation ofresidual activity day 7, day 17 Documentation ofcure rate or later'6293032). The characteristics of the excluded 18 Adverse events reported trials are listed in table III. *More relevant to good clinical practice than evaluation ofbias. The remaining seven trials were of acceptable methodological quality and had the cure rate on day 14 acceptable methodological quality, we selected those in as main outcome measure. 14 22-24 2728 36 Five of the trials which the main outcome measure was the cure rate at had an overall quality rating of low risk of bias, while 14 days after treatment. two had a moderate risk of bias (table II). Three trials were conducted in an area with high background prevalence of head lice (>50% of screened popu- Results lation).'4 2324 SELECTION OF TRIALS We identified 28 trials of clinical efficacy, 27 from RESULTS OF SELECTED TRIALS the computer databases'23 and one supplied by an In the seven selected trials 21 individual evaluations author in reply to our request.39 We also identified an of topical treatments were performed, comparing internal document of the Wellcome company placebo and eight compounds (lindane, bioresmethrin, describing a series of 1 1 small (11 < n < 74) unpublished chlorphenamide, 8-phenothrin, pyrethrin, malathion, comparative trials of permethrin and malathion carbaryl, and permethrin), and all but two evalu- performned between 1983