Evidence Report/Technology Assessment

Number 17

Management of Acne

Volume 1:  Evidence Report and Appendixes

Prepared  for:

Agency for Healthcare Research and Quality

Department of Health and Human Services

U.S. Public Health Service

2101 East Jefferson Street

Rockville, MD 20852

www.ahrq.gov

Contract No. 290-97-006

Prepared  by:

Johns Hopkins Evidence-based Practice Center

Harold P. Lehmann, M.D., Ph.D.

Principal Investigator

John S. Andrews, M.D.

Co-Principal Investigator

Karen A. Robinson, M.Sc.

Victoria L. Holloway, M.D., M.P.H.

Steven N. Goodman, M.D., Ph.D.

Investigators

AHRQ Publication No. 01-E019

September 2001

ISBN 1-58763-059-1

ISSN 1530-4396

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Preface

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based Practice Centers (EPCs), sponsors the development of evidence reports and technology

assessments to assist public- and private-sector organizations in their efforts to improve the

quality of health care in the United States. The reports and assessments provide organizations

with comprehensive, science-based information on common, costly medical conditions and new

health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to

developing their reports and assessments. 

To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into

collaborations with other medical and research organizations. The EPCs work with these partner

organizations to ensure that the evidence reports and technology assessments they produce will

become building blocks for health care quality improvement projects throughout the Nation. The

reports undergo peer review prior to their release.

AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by

providing important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality,

6010 Executive Blvd., Suite 300, Rockville, MD 20852.

Director							John M. Eisenberg, M.D.

Center for Practice and					Director

     Technology Assessment				Agency for Healthcare Research

Agency for Healthcare Research			     	     and Quality

     and Quality	

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Abstract

Objectives.  Acne is a common condition, particularly in adolescents and young adults, with potentially significant physical and psychological morbidity from scarring and from adverse

effects of treatment, as well as significant economic burdens. The purpose of this review was to

provide a comprehensive review of the literature on acne management.

Search strategy.  The following reference databases were searched: CENTRAL database of the Cochrane Collaboration (1948 through April, 1999), MEDLINE® (1966 through April, 1999), OLDMEDLINE (1960 through 1965), PsycINFO® (1887 through June, 1999), and CINAHL® (1982 through June 1999). The CENTRAL search strategy was (acne-vulgaris*.me OR

acne*.tw). Similar strategies were used for the other databases. The MEDLINE® strategy combined, using a Boolean AND, a topic-specific strategy (acne vulgaris [mh] OR acne* [tw])

with a strategy designed to retrieve all controlled trials.  Reference lists from key articles were

hand reviewed.

Selection criteria.  In consultation with our partners and technical experts, the following questions were formulated: What treatments are effective? What is the responsiveness of first-

line, second-line, and third-line treatments? What are the side effects of treatment?  Controlled

trials of acne therapy were sought that presented original, human data, written in English.

Data collection and analysis.  Identified articles were screened by independent reviewers in an abstract review process to determine eligibility for full article review. Eligible articles were

reviewed serially by two or more abstracters who sought methodological and outcome data. The

unit of analysis was the comparison between pairs of treatment arms. Comparisons were

qualitatively synthesized into conclusions for which there were varying levels of evidence.

Main results. Our searches identified 4,749 articles. After full article review, 250 articles reporting results of 274 controlled trials were included, from 31 countries. Of trials included, 74

percent reported data on subjects’ age, 13 percent reported on phase of care at study entry, 8

percent reported on race, and none reported on sexual maturity rating. Investigators used 25

assessment schemes to classify acne severity, and 505 distinctly named outcomes over 4 periods

of followup (usually ≤3 months). Two trials addressed psychological effects and 43 provided data concerning treatment compliance. None reported on cost. Only eight trials stratified results

by patient demographics and none by degree or type of prior therapy. Trials that had only

strengths numbered 45 (16 percent). Trials that had only weaknesses numbered 106 (39 percent).

Trials that had a mix of strengths and weaknesses numbered 101 (37 percent). The remaining 22

(8 percent) were of intermediate quality or did not provide enough information to make a

determination.

There were 250 pairwise comparisons of over 140 treatments. In grading the strength of

evidence, there were 14 comparisons with Level A, 102 with Level B, and 134 with Level C

evidence regarding effectiveness of treatment for acne. The Level A comparisons suggested the

greater effectiveness of  topical clindamycin, erythromycin, tetracycline, tretinoin, and 

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norgestimate/ethinyl estradiol over vehicle in mild-to-moderate acne; the greater effectiveness of

benzoyl peroxide and aluminum chlorhydroxide/sulphur over vehicle in unstated acne severity;

and equal effectiveness among topical tretinoin, isotretinoin, and motretinide. The following

Level A conclusions demonstrated equivalence: Benzoyl peroxide at various strengths was

equally efficacious in mild/moderate acne; adapalene and tretinoin were equally efficacious in

unspecificed severity; motretinide and tretinoin were equally effective; adding vitamin A to

oxytetracycline conferred no added efficacy; cyproterone was equally effective at two different

doses. For side effects data, 88 comparisons provided evidence for withdrawals, severe side

effects, or side effects in more than 10 percent of subjects in at least one arm. There were 10

comparisons of Level A strength.

Conclusions.  Despite the large number of English-language controlled trials regarding acne therapy, their methodological limitations prevent our ability to evaluate the comparisons among

therapies, and may limit the conclusions that others may draw in the future from this evidence

base, even when coupled with expert knowledge. Multiple treatments, inconsistent information

about baseline characteristics, and heterogeneity of assessment schemes and outcomes make it

difficult to synthesize the evidence about best approaches to acne management. For future

research to provide results for comparison, standardization among researchers is needed in these

different areas. Research is needed to define the optimal sequence of acne therapy, and to define

the relative roles of specialists and generalists in the care of acne. 

This report was developed using accepted evidence-based techniques; however, as in other

areas of research, the methodology was necessarily constrained by issues of feasibility and

practicality so that, for example, the analysis was limited to clinical trials reported in the English

language.  Nonetheless, this report is a systematic effort to collect and summarize the available

evidence on the management of acne and represents a potentially powerful resource for the field. 

As with any systematic review, to be accurate and comprehensive, the generation of guidelines

requires additional information, such as expert opinion, to put the evidence into context.

This document is in the public domain and may be used and reprinted without permission except for any copyrighted materials noted for which further reproduction is prohibited without the specific permission

of copyright holders.  AHRQ appreciates citation as to source, and the suggested format is provided

below:

Lehmann HP, Andrews JS, Robinson KA, et al. Management of Acne (Evidence Report/Technology

Assessment No. 17 (Prepared by Johns Hopkins Evidence-based Practice Center under Contract No. 290-

97-006). AHRQ Publication No. 01-E019. Rockville, MD: Agency for Healthcare Research and Quality.

September 2001.

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Contents

Structured Abstract	v

Summary	1

Evidence Report	5

Chapter 1. Introduction	7

	Epidemiology	7

	Disease Biology and Natural History	8

	Burden of Illness: Morbidity and Mortality	9

	Psychological Impact and Quality of Life	9

	Medical Costs	10

	Treatment of Acne	10

	Uses of This Report	11

Chapter 2. Methodology	13

	Recruitment of  Technical Experts	13

	Patient Population	13

	Questions	14

	Causal Pathway	14

	Literature Search Methods	16

		Sources	16

		Search Terms and Strategies	17

		Organization and Tracking of Literature Search	17

		Abstract Review	17

	Article Review	19

		Quality Assessment and Data Abstraction	19

		Article Review Process	20

	Peer Review	20

Chapter 3. Results: Summary of  Literature	23

	Literature Search and Abstract Review	23

	Article Review	23

	Description of the Acne Literature	24

		General Trial Information	24

		Patient Characteristics	26

		Acne Severity	27

		Source of Care	28

		Outcomes	29

		Treatments	29

Cbapter 4. Results: Evidence	47

	Summary of Evidence	47

		Overview	47

		Details	48

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	Summaries of Treatment Classes:	

		A..	Cleansers	49

		B.	Keratolytic (topical)	50

		C.	Anti-bacterial (topical)	54

		D.	Anti-bacterial (topical)/Keratolytic (topical) Combinations	61

		E.	Retinoid (topical)	69

		F.	Retinoid (topical)/Keratolytic	76

		G.	Retinoid (topical)/Anti-bacterial (topical)	77

		H.	Anti-bacterial (oral)	78

		I.	Anti-bacterial (oral)/Keratolytic (topical)	89

		J.	Anti-bacterial (oral)/Retinoid (topical)	90

		K.	Retinoid (oral)	90

		L.	Retinoid (oral)/Keratolytic	93

		M.	Anti-androgen	93

		N.	Other	99

	Psychological Outcomes	107

	Compliance	107

Chapter 5. Conclusions	127

	Characteristics of the Acne Clinical Research Literature	127

	Overarching Conclusions	127

	Answers to Specific Questions	128

		Primary Questions	128

		Secondary Questions	129

	Limitations	131

Chapter 6. Future Research	135

References	138

Appendixes	153

	A	Technical Experts and Peer Reviewers	155

	B.	Study Questions: Refinement by Experts	157

	C.	Study Questions	159

	D.	Study Questions: Expert Feedback	163

	E.	Search Terms and Strategies	165

	F.	Abstract Form	167

	G.	Article Review Forms	169

	H.	Included and Excluded Trials	185

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