Transcript Acne Core Outcomes Research Network

Acne Core Outcomes
Research Network
Diane Thiboutot, Alison Layton, Jerry Tan
Anne Eady, Marc Frey, Kathryn Gilliland, Mary Margaret Chren
NIAMS 1U01 AR065109-01
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
O
M
Core set – universally agreed and adopted
All outcomes – what is being
measured
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
YEAR
1
Define scope
1-3
Identify & involve
stakeholders
1-5
Identify core set of
outcome domains
3 - 10
Develop core set of validated
measurement methods
4 - 12
Disseminate
materials
4 onwards
Monitor adoption
ACORN
toolbox
ACORN’s scope & stakeholders
STAKEHOLDERS
SCOPE
Acne vulgaris but not
acne scarring
People with acne
Patients (1ary and 2ary care)
Patients (private practitioners,
aestheticians)
Clinical studies including
RCTs and, where
Those who self-treat
appropriate, routine
Regulatory agencies in each
clinical care
region
Universal (global)
Industry (pharma, cosmetic
adoption
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 site
Activities 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
Fading of existing spots
Reduced likelihood of acne recurring
Fewer areas of skin involved
Reduced visibility of spots
More confident
Improved condition of skin
Existing spots heal more quickly
Less severe spots
Reduced oiliness of skin
Fewer or less severe breakouts/flares
Reduced number of specific types…
Improved overall appearance
Less (severe) scarring
Improved texture of skin
Clear skin
Fewer new spots
Clearer skin
Less pain/discomfort
Smaller spots
Reduced redness/inflammation
Reduced number of spots
0
50
Number of respondents
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
Developing standardized assessments for acne clinical trials - your input is greatly
appreciated. https://www.surveymonkey.com/s/Acne_lesion_counting_survey
Analysis of initial
results from online
survey of clinical
investigators
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 site
Activities to date
Delphi process
online 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.
COMPAQ
Comprehensive acne quality of life instrument
 QoL impact of acne at face and torso
 Representation:
Age
Gender
Phototype
Report from Penn site
Activities 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 LLC
generously provided data
www.acnecoreoutcomes.org