There is a lack of evidence for benefit of any specific treatment for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).1 The purpose of this study is to survey North American dermatologists and burn surgeons in order to estimate the minimally clinical important difference (MCID) in key outcomes for assessing treatment efficacy in SJS/TEN. MCID provides a measure of the smallest change in a specific treatment outcome that clinicians perceive as important and practice-changing. MCID are needed to effectively evaluate treatment efficacy in a clinically meaningful way for physicians. Establishing the MCID is the first step in designing rigorous randomized controlled trials to evaluate treatments for SJS/TEN. There is a lack of clinical trials for these life-threatening conditions, and this study lays the essential groundwork for future trial design.
A survey was designed to estimate MCID values for: (1) length of time to achieve full re-epithelialization (complete healing); (2) length of time before cessation of disease progression; (3) length of hospital stay; and (4) rate of mortality. The confidential and anonymous survey was electronically disseminated to a total of 928 dermatologists and burn surgeons who specialize in SJS/TEN care across North America. Participants were identified through registries from specialty-specific associations including the Canadian Dermatology Association, American Burn Association, and contact lists of North American physicians from previous survey efforts on SJS/TEN. A total of 190 physicians completed the survey using SurveyMonkey (response rate of 20.5%). Weighted means with standard deviations and standard errors of the mean were used. Demographics of survey participants are summarized in Table 1.
Table 1.
Demographics of 190 physician survey participants
| Variable | Value, No. (%) |
|---|---|
| Field of specialty | |
| Dermatology | 78 (44.3) |
| Burn Surgery | 93 (52.8) |
| Other | 5 (2.84) |
| Critical Care | 4 (2.27) |
| Pediatric Critical Care | 1 (0.57) |
| Number of years in practice | |
| 1–9 | 77 (44) |
| 10–19 | 35 (20) |
| 20–29 | 31 (17.7) |
| 30–39 | 23 (13.1) |
| 40–49 | 8 (4.57) |
| Other | 1 (0.57) |
| >60 | 1 (0.57) |
| Number cases in past 1 year | |
| 1–4 | 46 (29.3) |
| 5–9 | 50 (31.8) |
| 10–14 | 40 (25.5) |
| 15–19 | 14 (8.92) |
| 20–24 | 5 (3.18) |
| Other | 1 (0.64) |
| >24 | 1 (0.64) |
The estimated MCID for full re-epithelialization (complete healing) was 3.2 ± 1.8 days (SEM 0.7). The estimated MCID for time to cessation of disease progression was 2.1 ± 1.5 days (SEM 0.7). The estimated MCID for time reduction in length of hospital stay was 2.7 ± 1.6 days (SEM 0.7). The estimated MCID for reduction in rate of mortality falls in between 2–5% and 6–10% range; hence, the estimate was no greater than 10% and no less than 2%.
With this survey data, we define a set of MCID estimates for treatment outcomes specific to SJS/TEN. Our study estimated the MCID values from weighted means with standard deviations to provide a clinically meaningful consensus estimate (Figure 1). As perceived by physicians, these values would constitute clinically important changes required to change practice in the management of SJS/TEN.
Figure 1.
Standard curves for time to re-epithelialization, cessation of disease progression, and length of hospital stay
The strengths of the study are the large size of cohort, high response rate, representativeness, and reproducibility of the survey. However, MCID estimates are not easily verifiable against external objective measures. In addition, the cross-sectional survey design can introduce biases such as recall bias.
Our study is the first to estimate the MCIDs in treatment outcomes for SJS/TEN. This study defines consensus parameters that are necessary to (1) calculate samples size for prospective studies and (2) evaluate treatment outcomes for SJS/TEN. These findings are necessary to design randomized trials and interpret their results in a clinically meaningful way that can ultimately influence clinical practice.
Acknowledgement:
The authors would like to thank Katie D. White, Canadian Dermatology Association and American Burn Association for their assistance with the survey.
Funding Statement:
Funding was not provided in support of completion of this manuscript and the research contained herein. Resources for other related work have been awarded by the Canadian Dermatology Foundation and The Ottawa Hospital Department of Medicine.
Footnotes
Conflict of Interest Statement:
The authors have no conflicts of interest to declare.
Statement of Prior Presentation:
The work here has not been previously published or presented.
Contributor Information
Whan B Kim, The Ottawa Hospital, Division of Dermatology, Department of Medicine, Ottawa, Canada..
Brandon Worley, University of Ottawa, Canada..
James Holmes, IV, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA..
Elizabeth J Phillips, Department of Medicine, Vanderbilt University Medical Center and Institute for Immunology & Infectious Diseases, Murdoch University, Perth, Western Australia..
Jennifer Beecker, The Ottawa Hospital, Division of Dermatology, Department of Medicine, University of Ottawa, The Ottawa Hospital Civic Campus, 4th Floor, 737 Parkdale Avenue, Ottawa, Ontario K1Y-1J8, Canada, Ottawa Hospital Research Institute, K1H 8L6 Ottawa, Canada, University of Ottawa, K1H 8L6 Ottawa, Canada.
REFERENCES
- 1.Sekula P, Dunant A, Mockenhaupt M, Naldi L, Bouwes Bavinck JN, Halevy S, Kardaun S, Sidoroff A, Liss Y, Schumacher M, Roujeau JC, RegiSCAR study group (2013) Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol. 133(5):1197–204. [DOI] [PubMed] [Google Scholar]