Published on in Vol 5, No 1 (2022): Jan-Mar

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Mortality Outcomes in Dermatology: An Exploration of Core Outcome Sets and Cochrane Skin Systematic Reviews

Mortality Outcomes in Dermatology: An Exploration of Core Outcome Sets and Cochrane Skin Systematic Reviews

Mortality Outcomes in Dermatology: An Exploration of Core Outcome Sets and Cochrane Skin Systematic Reviews

Research Letter

1Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States

2Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

3Department of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada

Corresponding Author:

Torunn E Sivesind, MD

Department of Dermatology

University of Colorado Anschutz Medical Campus

1665 Aurora Ct

Aurora, CO, 80045

United States

Phone: 1 916 474 9963

Fax:1 720 667 3887


Cochrane has been a trusted proponent of evidence-based medicine for over 20 years. Its dermatology-specific editorial team (Cochrane Skin Review Group) is the pre-eminent source of systematic reviews in dermatology [1]. Explicit standardized Cochrane review methods can minimize bias and maximize the reliability of reported outcomes, establishing benchmarks for decision-making. Mortality is one outcome where pronounced heterogeneity in reporting may affect its utility in clinical research. We therefore explored mortality outcome expression and execution in the Cochrane Skin portfolio and concurrently analyzed mortality in core outcome sets (outcomes that, at a minimum, should be measured in clinical trials) by searching dermatology studies registered in the COMET (Core Outcome Measures in Effectiveness Trials) database [2]. COMET contains text from core outcome sets publications, from which we extracted core outcomes and classified these according to the taxonomy developed by Dodd et al [3] for validated standardized annotation.

All Cochrane Skin Group reviews as of March 2021 were included and exported from the Cochrane Database of Systematic Reviews [1], allowing descriptive analysis and characterization of mortality reporting by category of mortality terminology (all-cause, cause-specific, infant/maternal, survival). All COMET database core outcome sets classified in the published “skin” research category as of August 23, 2021, were reviewed for reporting of mortality outcomes and categorized according to the mortality terminology previously described. Core outcomes specified in terms of “death” were included in the all-cause mortality category.

Of the 113 Cochrane Skin dermatology reviews, 13 reported mortalities as an outcome measure: 10 all-cause, 2 cause-specific, 5 survival, and 1 infant/maternal (Table 1).

Four reviews (4/13) reported more than one mortality outcome. More than one-third of the total reviews (5/13) were melanoma-related. Reviews of other dermatologic conditions reporting mortality included cutaneous squamous cell carcinoma (cSCC), nonmelanoma skin cancer, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, toxic epidermal necrolysis (TEN), necrotizing fasciitis, drug-induced skin rash, and topical steroids used during pregnancy. The time frame of mortality outcome reporting ranged widely, from 10 days to 10 years, but generally correlated appropriately with the condition (eg, 30 days for TEN capturing acute onset and progression vs 10-year survival for melanoma).

COMET database searches revealed 13 core outcome set studies of 13 skin conditions (Table 2); only 2 (15%) included mortality as a core outcome (survival for head and neck lymphatic malformations, death from cSCC).

Table 1. Mortality reporting in Cochrane Skin Systematic Reviews as of March 2021.
ConditionCochrane Systematic Review titleAuthorsYearDOIPMIDType of mortality reportedTime frame of mortality reporting
Toxic epidermal necrolysisInterventions for Toxic Epidermal NecrolysisMajumdar S, Mockenhaupt M, Roujeau J, Townshend A200210.1002/14651858.CD00143512519556All-cause mortality30-day follow-up time
MelanomaStatins and Fibrates for Preventing MelanomaDellavalle RP, Drake A, Graber M, Heilig LF, Hester EJ, Johnson KR, McNealy K, Schilling L200510.1002/14651858.CD003697.pub216235336Disease-specific≥7 years post-RCTa
Nonmelanoma skin cancersInterventions for Preventing Nonmelanoma Skin Cancers in High-Risk GroupsBath-Hextall F, Leonardi-Bee J, Somchand N, Webster A, Delitt J, Perkins W200710.1002/14651858.CD005414.pub217943854All-cause mortalityEnd of trial follow-up (1 year to 5 years for included RCTs)
Pemphigus vulgaris and pemphigus foliaceusInterventions for Pemphigus Vulgaris and Pemphigus FoliaceusMartin LK, Agero AL, Werth V, Villanueva E, Segall J, Murrell DF200910.1002/14651858.CD006263.pub219160272All-cause mortalityVariable, deaths only reported from 1 RCT over 4 weeks
MelanomaSurgical Excision Margins for Primary Cutaneous MelanomaSladden MJ, Balch C, Barzilai DA, Berg D, Freiman A, Handiside T, Hollis S, Lens MB, Thompson JF200910.1002/14651858.CD004835.pub219821334All-cause mortality, survival, recurrence-free survival5- and 10-year survival
Bullous pemphigoidInterventions for Bullous PemphigoidKirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP201010.1002/14651858.CD002292.pub320927731All-cause mortality51 days (1 RCT), 10 days (1 RCT), 6 months and 3 years (1 RCT)
Cutaneous squamous cell carcinomaInterventions for Nonmetastatic Squamous Cell Carcinoma of the SkinLansbury L, Leonardi-Bee J, Perkins W, Goodacre T, Tweed JA, Bath-Hextall FJ201010.1002/14651858.CD007869.pub220393962All-cause mortality2 years
MelanomaInterferon Alpha for the Adjuvant Treatment of Cutaneous MelanomaMocellin S, Lens MB, Pasquali S, Pilati P, Chiarion Sileni V201310.1002/14651858.CD008955.pub223775773Death, disease-free survival, overall survival5 years
MelanomaSentinel Lymph Node Biopsy Followed by Lymph Node Dissection for Localized Primary Cutaneous MelanomaKyrgidis A, Tzellos T, Mocellin S, Apalla Z, Lallas A, Pilati P, Stratigos A201510.1002/14651858.CD010307.pub225978975All-cause mortality, disease-specific, disease-free survival10 years
PregnancySafety of Topical Corticosteroids in PregnancyChi CC, Wang SH, Wojnarowska F, Kirtschig G, Davies E, Bennett C201510.1002/14651858.CD007346.pub326497573Fetal deathNot specified, variable
Necrotizing soft tissue infectionsInterventions for Necrotizing Soft Tissue Infections in AdultsHua C, Bosc R, Sbidian E, De Prost N, Hughes C, Jabre P, Chosidow O, Le Cleach L201810.1002/14651858.CD011680.pub229851032Mortality, survival30-day mortality, 28-day and 30-day study periods for survival
MelanomaSystemic Treatments for Metastatic Cutaneous MelanomaPasquali S, Hadjinicolaou AV, Chiarion Sileni V, Rossi CR, Mocellin S201810.1002/14651858.CD011123.pub229405038Overall survival, progression-free survival1 year
Severe drug‐induced skin rashGenetic Testing for Prevention of Severe Drug‐Induced Skin RashAlfirevic A, Pirmohamed M, Marinovic B, Harcourt-Smith L, Jorgensen AL, Cooper TE201910.1002/14651858.CD010891.pub231314143All-cause mortality12-month follow-up post rash

aRCT: randomized controlled trial.

Table 2. Mortality as an Outcome in COMET (Core Outcome Measures in Effectiveness Trials).
ConditionStudy titleAuthorsYearURLDOIMortality as an outcome (yes/no)Type of mortality reported
AcneIdentifying What to Measure in Acne Clinical Trials: First Steps Towards Development of a Core Outcome SetLayton AM, et al2017
Actinic keratosisCore Outcome Set for Actinic Keratosis Clinical TrialsReynolds KA, et al2019
Cutaneous leishmaniasisHarmonized Clinical Trial Methodologies for Localized Cutaneous Leishmaniasis and Potential for Extensive Network With Capacities for Clinical EvaluationOlliaro P, et al2018
EczemaCore Outcome Domains for Controlled Trials and Clinical Recordkeeping in Eczema: International Multiperspective Delphi Consensus ProcessSchmitt J, et al2011
Head and neck lymphatic malformationStandardized Outcome and Reporting Measures in Pediatric Head and Neck Lymphatic MalformationsBalakrishnan K, et al2015
Hidradenitis suppurativaA Core Domain Set for Hidradenitis Suppurativa Trial Outcomes: An International Delphi ProcessThorlacius L, et al2018
Incontinence-associated dermatitisCore Outcome Domains in Incontinence-Associated Dermatitis ResearchVan den Bussche K, et al2018
PsoriasisIdentifying a Core Domain Set to Assess Psoriasis in Clinical TrialsCallis Duffin K, et al2018 availableNoN/A
Skin cancerDevelopment of a Core Outcome Set for Cutaneous Squamous Cell Carcinoma Trials: Identification of Core Domains and OutcomesReynolds KA, et al2020 survival, recurrence-free survival, disease-specific survival
Vascular malformationsDevelopment of an International Core Outcome Set for Peripheral Vascular Malformations (OVAMA Project)Horbach SER, et al2018
Vasculitis (small-vessel/ ANCAb-associated)Clinicians’ Perspective on Key Domains in ANCA-Associated Vasculitis: a Delphi ExerciseMilman N, et al2017 discussed (from OMERACTc, to which this study adds—but was not directly included in this study)
VitiligoDeveloping Core Outcome Set for Vitiligo Clinical Trials: International e-Delphi ConsensusEleftheriadou V, et al2015
Vulval skin disordersOutcome Measures for Vulval Skin Conditions: a Systematic Review of Randomised Controlled TrialsSimpson R, et al2013

aN/A: not applicable.

bANCA: antineutrophil cytoplasmic autoantibody.

cOMERACT: Outcome Measures in Rheumatoid Arthritis Clinical Trials.

Although limited in the number of studies appraised, our results illustrate substantial variability in the reporting and timing of mortality outcomes in Cochrane Skin reviews and COMET dermatology-related core outcome sets. Allowance of potentially unclear metrics (eg, “death”) and fluctuations in the time frame considered (especially within studies of a particular disease) may be detrimental to the downstream harmonization and generalizability of research findings. Guidelines to assist researchers during trial design and registration would encourage the selection of clear metrics and facilitate consistent outcome reporting at the later stages. Increased guidance and communication among stakeholders in this area, including further refinement of reporting guideline statements such as CONSORT (Consolidated Standards of Reporting Trials) [4] and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [5], could promote much-needed standardization in mortality reporting, facilitating comparison across studies and helping decision makers effectively use dermatology research.


The authors wish to acknowledge Eve Tomlinson, Jordi Pardo, Susanna Dodd, Nicole Skoetz, and George Wells, whose contributions to a Cochrane health equity priority-setting pilot exercise laid the foundation for examining mortality outcomes across the entire Cochrane Library and provided the impetus for this smaller scale study of dermatology-related Cochrane reviews and core outcome sets.

Conflicts of Interest

RPD is Editor in Chief of the JMIR Dermatology, a Joint Coordinating Editor for Cochrane Skin, a dermatology section editor for UpToDate, a Social Media Editor for the Journal of the American Academy of Dermatology (JAAD), and a Podcast Editor for the Journal of Investigative Dermatology (JID). He is a coordinating Editor Representative on Cochrane Council. TES is an Editorial Board Member-at-Large for JMIR Dermatology. RPD receives editorial stipends (JAAD, JID), royalties (UpToDate), and expense reimbursement from Cochrane Skin. TES receives fellowship funding from the Pfizer Global Medical Grant (58858477) Dermatology Fellowship 2020 (principal investigator RPD), and fees for serving as a Medical Advisor and Investigator for Antedotum Inc. MDS is a member of the Cochrane Collaboration.

  1. Cochrane Database of Systematic Reviews. Cochrane Library. 2021.   URL: [accessed 2021-08-24]
  2. Advanced search. COMET Initiative.   URL: [accessed 2021-08-23]
  3. Dodd S, Clarke M, Becker L, Mavergames C, Fish R, Williamson PR. A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery. J Clin Epidemiol 2018 Apr;96:84-92 [FREE Full text] [CrossRef] [Medline]
  4. Ioannidis JPA, Evans SJW, Gøtzsche PC, O'Neill RT, Altman DG, Schulz K, CONSORT Group. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med 2004 Nov 16;141(10):781-788 [FREE Full text] [CrossRef] [Medline]
  5. Zorzela L, Loke YK, Ioannidis JP, Golder S, Santaguida P, Altman DG, PRISMAHarms Group. PRISMA harms checklist: improving harms reporting in systematic reviews. BMJ 2016 Feb 01;352:i157. [CrossRef] [Medline]

COMET: Core Outcome Measures in Effectiveness Trials
CONSORT: Consolidated Standards of Reporting Trials
cSCC: cutaneous squamous cell carcinoma
JAAD: Journal of the American Academy of Dermatology
JID: Journal of Investigative Dermatology
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
TEN: toxic epidermal necrolysis

Edited by G Eysenbach; submitted 07.10.21; peer-reviewed by F Beyer, M Mahmic Kaknjo; comments to author 10.12.21; revised version received 17.12.21; accepted 20.12.21; published 01.02.22


©Torunn E Sivesind, Mindy D Szeto, Shahzeb Hassan, Peter Tugwell, Robert P Dellavalle. Originally published in JMIR Dermatology (, 01.02.2022.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Dermatology Research, is properly cited. The complete bibliographic information, a link to the original publication on, as well as this copyright and license information must be included.