Acne Core Outcomes Research Network

NIAMS 1U01 AR065109-01

Diane Thiboutot, Alison Layton, Jerry TanAnne Eady, Marc Frey, Kathryn Gilliland, Mary Margaret Chren

Developing Standardized Outcome Measures for Acne Clinical Trials: Rationale

Many different grading scales are used in clinical trials for acne

This doesn’t allow for comparison of data across drug trials

Having a standard set of outcome measures (grading scales, QoL) will allow these comparisons to be made without having to do costly head-to-head studies

ACORN Project Aims

Develop an online training module for acne lesion counting including a standardized way to present trial data Standardized Instrument for Lesion Counting in Acne

(SILCA)

Develop a comprehensive acne quality of life instrument Comprehensive Acne Quality of Life (CompAQ)

Develop and evaluate standardized scale (s) for global assessment of acne

Evaluate novel technologies to assess acne

ACORN working groups Team Harrogate (UK)

Alison Layton, MD

Anne Eady, PhD

Martin Bland, PhD (statistician consultant)

Team Penn State (USA)

Me

Kathy Gilliland

John Quiring, PhD (statistician consultant)

Andrea Zaenglein, MD

Esther Delll, MS (librarian)

Team Windsor (Canada)

Jerry Tan

Marc Frey, PhD candidate

UCSF

Meg Chren, MD

Other US and international members

www.acnecoreoutcomes.org

Concept of core sets of outcomes & measures

Core set – universally agreed and adopted

All outcomes – what is being measured

O M

All instruments – ways of measuring different outcomes

Core outcome measure sets in practice

Minimum set of outcomes that should be measured and reported in all late phase clinical trials

Whenever a core outcome is included in a trial, it should be measured by all investigators using the same standardised method or validated instrument The core set of outcome measures will not include

more than one way of measuring the same thing If other outcomes are included in an acne RCT, they too

should ultimately be measured in a standardised way (e.g. sebum secretion) Not an immediate goal of ACORN but part of the

ACORN concept of a toolbox of validated measures

The HOME roadmap

Key features

Global stakeholder representation and involvement

Consensus-derived

Evidence-based

Universally applicable

1. Identification of essential domains (what will be measured) – essentially outcomes of interest

2. Identification (via systematic reviews) or development de novo of validated instruments to measure the core domains

Summary of HOME roadmap

Define scope

Identify & involve stakeholders

Identify core set of outcome domains

Develop core set of validated measurement methods

Disseminate materials

Monitor adoption

YEAR

1

1 - 3

1 - 5

3 - 10

4 - 12

4 onwards

ACORN toolbox

ACORN’s scope & stakeholders

SCOPE Acne vulgaris but not

acne scarring Clinical studies

including RCTs and, where appropriate, routine clinical care

Universal (global) adoption

STAKEHOLDERS People with acne

Patients (1ary and 2ary care) Patients (private

practitioners, aestheticians) Those who self-treat

Regulatory agencies in each region

Industry (pharma, cosmetic companies, device manufacturers)

Acne researchers

Main stages of the HOME roadmap I

IDENTIFY CORE DOMAINS (WHAT TO MEASURE)• Symptoms and signs

• Impacts

• Changes expected in each

Assess the relative importance of each Derive minimum set of outcome domains • Using consensus-based methods

• Involving all types of stakeholder

• Internationally representative

MIXED METHODS APPROACH: systematic reviews, surveys/questionnaires, Delphi exercises, consultation with experts

Report from Harrogate siteActivities to date

Progress to date

Development of SILCA (Standardisation of Lesion Counting in Acne) aims:- Web-based teaching and evaluation modules Training videos available via YouTube Hard copy manual

Processes to underpin the development of SILCA A systematic review of acne RCTs

Patient reported outcomes question Professional survey

Methods of data analysis

Why focus on lesion counts? Most widely used outcome measure in acne RCTs

Can justify inclusion in core outcome measure set on basis of universal adoption

Have additional patient data from Acne PSP to support this decision

Can fast-track through roadmap

Conduct, analysis and reporting not standardised Zarchi & Jemec (Curr Derm Rep 2012;1:131-6) found lesion counts had

been reported in 25 different ways in a snapshot of 18 trials published in 2011.

Quality of studies using manual lesion counts highly variable Conducting a systematic review to demonstrate this

Automated methods under development but none yet sufficiently developed for universal adoption Standardisation is still relevant

Review of RCTs - Take-home messages Lesion counting is almost universally used as an

outcome measure Methods used to analyse and report counts are

not standardised Validates designation of lesion counting as a

core outcome measure and development of SILCA to harmonise methods Patient endorsement would be a ‘nice to have’

Outcomes question:Acne Priority Setting Partnership

Embedded the following question in the online survey to identify acne treatment uncertainties: “Please tell us in your own words how you decide if your

treatment has been effective.”

Obtained 710 usable responses 84.6% female 47% aged 16-24 1 in 5 non-white 1 in 4 lived outside the UK

Symptom or impact-related outcomes

Number of respondents

Reduced number of spots

Less pain/discomfort

Clear skin

Improved overall appearance

Reduced oiliness of skin

Improved condition of skin

Fewer areas of skin involved

0 50 100 150 200 250

Conduct of counts:aspects where there is consensus

Position of the patient Types of patient to exclude from efficacy

RCTs Use of a facial template showing areas to

count Counting PA, PU, OC and CC separately – but

not often reported this way and requires more training

How to identify nodules Exclusion of macules from IL count

Developing standardized assessments for acne clinical trials - and your input is greatly appreciated. https://www.surveymonkey.com/s/Acne_lesion_counting_survey

Conduct of counts – aspects requiring standardisation Lighting Preparation of the subject Whether and when to use a magnifying lens Whether to stretch the skin Whether to include macrocomedones in

lesion counts What to do about lesions on the nose Recording of counts

Analysis of initial results from online survey of clinical investigators

Developing standardized assessments for acne clinical trials - your input is greatly appreciated. https://www.surveymonkey.com/s/Acne_lesion_counting_survey

Methods of data analysis and presentation Consulting with expert statisticians underway Preliminary findings are:

Always report median and mean ± SD Include absolute and % change from baseline Report results of ITT and PP analyses Use LOCF for missing values if N≤50 per arm and

multiple imputation if N>50 ANCOVA is the method of choice for significance

testing - apply appropriate test for skewness before using If counts are positively skewed, use rank based

method

Report from Windsor siteActivities to date

Delphi processonline small sample survey technique

PATIENTS

In what ways has acne affected you and your life?

DERMATOLOGISTS In what ways has acne

affected your patients and their lives?

Purpose:

1. compare treatment expectations between patients and experts

2. assist patients in determining treatment options that meet their

personal needs.

3. inform future measures that target the quality of life aspects

related to acne. 

COMPAQComprehensive acne quality of life instrument

QoL impact of acne at face and torso Representation:

Age Gender Phototype

Report from Penn siteActivities to date

Progress to date: A group effort!

Systematic review of acne impacts (100 articles extracted)

Early draft of the SILCA module prepared Photo selection in progress

Video segments to be filmed June 2015

Statistical consultations in progress

Evaluation of acne lesion counting computer algorithm 6/34 subjects enrolled

Challenges with higher phototype skin

Next Steps: Expanding the network and building international consensus

Would like to engage your participation in our activities Delphi processes and surveys Assistance with systematic reviews Contribution of content to our website Participation in working groups/meetings

Interested? Sign up at www.acnecoreoutcomes.org

ACORN meeting at the World Congress of Dermatology Vancouver

SAVE THE DATE: Monday June 8, 2015, 10.00 – 13.00 Location: Vancouver International Film Center, World Congress

of Dermatology, Vancouver, BC

  To register, please visit: www.physicianresources.org/invites/ACORN

Acknowledgements: ACORN partners

Valeant Pharmaceutical North America LLCgenerously provided data

www.acnecoreoutcomes.org