Core Outcome Set for Actinic Keratosis Clinical Trials

Abstract

IMPORTANCE Although various treatments have been found in clinical trials to be effective in treating actinic keratosis (AK), researchers often report different outcomes. Heterogeneous outcome reporting precludes the comparison of results across studies and impedes the synthesis of treatment effectiveness in systematic reviews.OBJECTIVE To establish an international core outcome set for all clinical studies on AK treatment using systematic literature review and a Delphi consensus process.EVIDENCE REVIEW Survey study with a formal consensus process. The keywords actinic keratosis and treatment were searched in PubMed, Embase, CINAHL, and the Cochrane Library to identify English-language studies investigating AK treatments published between January 1, 1980, and July 13, 2015. Physician and patient stakeholders were nominated to participate in Delphi surveys by the Measurement of Priority Outcome Variables in Dermatologic Surgery Steering Committee members. All participants from the first round were invited to participate in the second round. Outcomes reported in randomized controlled clinical trials on AK treatment were rated via web-based e-Delphi consensus surveys.Stakeholders were asked to assess the relative importance of each outcome in 2 Delphi survey rounds. Outcomes were provisionally included, pending the final consensus conference, if at least 70% of patient or physician stakeholders rated the outcome as critically important in 1 or both Delphi rounds and the outcome received a mean score of 7.5 from either stakeholder group. Data analysis was performed from November 5, 2018, to February 27, 2019.FINDINGS A total of 516 outcomes were identified by reviewing the literature and surveying key stakeholder groups. After deduplication and combination of similar outcomes, 137 of the 516 outcomes were included in the Delphi surveys. Twenty-one physicians and 12 patients participated in round 1 of the eDelphi survey, with 17 physicians (81%) retained and 12 patients (100%) retained in round 2. Of the 137 candidate outcomes, 9 met a priori Delphi consensus criteria, and 6 were included in the final outcomes set after a consensus meeting: complete clearance of AKs, percentage of AKs cleared, severity of adverse events, patient perspective on effectiveness, patient-reported future treatment preference, and recurrence rate. It was recommended that treatment response be assessed at 2 to 4 months and recurrence at 6 to 12 months, with the AK rate of progression to cutaneous squamous cell carcinoma reported whenever long-term follow-up was possible.CONCLUSIONS AND RELEVANCE Consensus was reached regarding a core outcome set for AK trials. Further research may help determine the specific outcome measures used to assess each of these outcomes.

Actinic cheilitis: a systematic review of treatment options

“…Outcome measures that were assessed in the studies included scarring, healing time, histological assessment, patient satisfaction and re‐epithelialization time. These outcome measures were similar to the recently established core outcome set for treatment of actinic keratoses and are included in Table 2 11 . The majority of studies reported on clearance, recurrence or progression rates, on adverse events (AEs), long‐term follow‐ups, cosmetic outcomes, patient satisfaction and some reported on treatment discontinuation, dosage adherence or healing time.…”

“…Additionally, we assessed the adverse effects of these treatment modalities. We also evaluated the reporting of the recently defined core outcome set of actinic keratoses (complete clearance, treatment percentage of actinic keratoses cleared, severity of adverse events, patient perspective on effectiveness, patient‐reported future treatment preferences and recurrence rates) 11 …”

“…Evidence on the efficacy of treatment options is sparse and relies on case series and pooled summaries 9,10 . Recently core outcome sets were defined for actinic keratosis, to be reported in clinical studies and categorized in three levels (the core outcome set, outcomes when long‐term follow‐up is possible, and important but not required outcomes) 11 …”

Treatment Motivations and Expectations in Patients with Actinic Keratosis: A German-Wide Multicenter, Cross-Sectional Trial

“…Besides, these factors are important to improve the acceptability of and compliance to treatment regimens [11,12]. Surprisingly, the patient-centered motives and expectations towards AK treatment have received little attention until now but can represent a major barrier for treatment adherence [13][14][15]. Here, we report the results of a German-wide, multicenter, cross-sectional study to gain insight into the management of AK by investigating patient attitudes, expectations, and motives.…”

Use of complete clearance for assessing treatment efficacy for 5-fluorouracil interventions in actinic keratoses: how baseline lesion count can impact this outcome

“…An international core outcome set for all clinical trials on AK treatment has been recently published by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative and the Cochrane Skin Group Core Outcomes Set Initiative (CSG-COUSIN). Core outcome set parameters included percentage of AKs cleared, complete clearance of AKs, severity of adverse events, patient perspective on effectiveness, patient-reported future treatment preference, and rate of occurrence [ 18 ]. The international experts and patients recognized the importance of including the efficacy endpoint ‘percentage of AKs cleared’ in their core outcome set.…”