COA regulatory submissions and support

Appropriate clinical outcome assessment (COA) label claims rely on robust instrument selection, development and validation to a standard that meets current regulatory expectations. Regulatory approval is dependent on assessment of relevant and important outcomes (the ‘concept of interest’) in the right population (‘context of use’) to capture the true treatment benefit.

Our team brings years of experience in helping to deliver regulatory success through strategic consulting, development of dossiers and briefing books, regulatory meeting support and attendance, Drug Development Tool (DDT) qualification and more. We are highly experienced in developing COA dossiers and other regulatory briefing books that are in line with the expectations of the Food and Drug Administration (FDA) Division of Clinical Outcome Assessment (DCOA), European Medicines Agency (EMA) and other international regulatory agencies and reimbursement authorities; facilitating efficient and productive regulatory interactions, and ultimately helping clients to gain approval for targeted label claims.

“The concept elicitation research is complete and adequately explores the areas of pain…”

“The sample for concept elicitation was adequate… The FDA concurs with the proposed recall period and reporting frequency.”

“Does the Agency concur with the proposed plans for psychometric evaluation? ‘Overall, yes. FDA appreciates the Sponsor’s discussion of ensuring the instruments’ ability to detect change.’”

“We agree with the sponsor’s plan to employ a mixed methods approach using Rasch analysis in addition to other methods to establish content validity.”

“The Sponsor’s work demonstrates the content validity of the items and domain.”

“In general, we have found your qualitative work to date complete, well-executed and carefully analysed.”

“Your proposal to use the composite strategy for your primary estimand appears reasonable”

“These instruments have demonstrated adequate evidence of content validity and cross-sectional measurement properties.”

Regulatory success

COA

Rinvoq (upadacitinib) for adolescents and adults with moderate to severe atopic dermatitis (EMA 2021; FDA 2022)

Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain (FDA and EMA)
Atopic Dermatitis Impact Scale (ADerm-IS) Sleep domain (EMA only)
Worst Pruritis NRS (FDA and EMA)

Rinvoq (upadacitinib) for adolescents and adults with moderate to severe Ulcerative Colitis (FDA 2022)

Abdominal Pain Diary Item (FDA)
Bowel Urgency Diary Item (FDA)

NUCALA for the treatment of chronic rhinosinusitis with nasal polyps (FDA 2021; EMA 2022)

Nasal obstruction VAS (FDA & EMA)
Loss of smell VAS (FDA & EMA)
Nasal discharge VAS (FDA only)
Mucus in throat VAS (FDA only)
Facial pain VAS (FDA only)
Overall VAS score (EMA only)
Composite VAS score (EMA only)
SNOT-22 total score (EMA only)

Adbry® for the treatment of moderate-to-severe atopic dermatitis in adult patients (2021)

Worst Daily Pruritus NRS

Arcalyst (rilonacept) for adolescents and adults with recurrent pericarditis (FDA 2021)

Pericarditis Pain NRS

Dupixent (dupilumab) for children 6-11 years old with moderate to severe asthma (FDA 2021)

Asthma Control Questionnaire-7-Interviewer Administered (ACQ-7-IA)
Pediatric Asthma Quality of Life Questionnaire with Standardized Activities Interviewer Administered (PAQLQ(S)-IA)

Xywav oral solution for treating idiopathic hypersomnia in adultsIdiopathic hypersomnia for adults (FDA 2021)

Epworth sleep scale
PGIC
Idiopathic Hypersomnia Scale

Botox® for satisfaction in the appearance of facial lines (2017)

Facial Line Satisfaction Questionnaire (FLSQ)

Humira® (adalimumab) for hidradenitis suppurativa (2016)

Hidradenitis Suppurative Clinical Response (HiSCR)

Nothera® (droxidopa) for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about the black out” in adult patients with symptomatic neurogenic orthostatic hypotension (2014)

Orthostatic Hypotension Symptom Assessment (OHSA)

Cosentyx® (secukinumab) for moderate to severe plaque psoriasis (2015)

Psoriasis symptom diary (PSD)

Kybella® (deoxycholic acid) for the improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults (2015)

Clinical Reported Submental Fat Rating Scale (CR-SMFRS)
Patient Reported Submental Fat Rating Scale (PR-SMFRS)
Patient Reported Submental Fat Impact Scale (PR-SMFIS)

Jakafi® (ruxolitinib) for myelofibrosis (2011)

Myelofibrosis Symptom Assessment Form version 2.0 diary (MF-SAF v2.0 diary)

Regulatory success and COA

Rinvoq (upadacitinib) for adolescents and adults with moderate to severe atopic dermatitis (EMA 2021; FDA 2022)

Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain (FDA and EMA)
Atopic Dermatitis Impact Scale (ADerm-IS) Sleep domain (EMA only)
Worst Pruritis NRS (FDA and EMA)

Rinvoq (upadacitinib) for adolescents and adults with moderate to severe Ulcerative Colitis (FDA 2022)

Abdominal Pain Diary Item (FDA)
Bowel Urgency Diary Item (FDA)

NUCALA for the treatment of chronic rhinosinusitis with nasal polyps (FDA 2021; EMA 2022)

Nasal obstruction VAS (FDA & EMA)
Loss of smell VAS (FDA & EMA)
Nasal discharge VAS (FDA only)
Mucus in throat VAS (FDA only)
Facial pain VAS (FDA only)
Overall VAS score (EMA only)
Composite VAS score (EMA only)
SNOT-22 total score (EMA only)

Adbry® for the treatment of moderate-to-severe atopic dermatitis in adult patients (2021)

Worst Daily Pruritus NRS

Arcalyst (rilonacept) for adolescents and adults with recurrent pericarditis (FDA 2021)

Pericarditis Pain NRS

Dupixent (dupilumab) for children 6-11 years old with moderate to severe asthma (FDA 2021)

Asthma Control Questionnaire-7-Interviewer Administered (ACQ-7-IA)
Pediatric Asthma Quality of Life Questionnaire with Standardized Activities Interviewer Administered (PAQLQ(S)-IA)

Xywav oral solution for treating idiopathic hypersomnia in adultsIdiopathic hypersomnia for adults (FDA 2021)

Epworth sleep scale
PGIC
Idiopathic Hypersomnia Scale

Botox® for satisfaction in the appearance of facial lines (2017)

Facial Line Satisfaction Questionnaire (FLSQ)

Humira® (adalimumab) for hidradenitis suppurativa (2016)

Hidradenitis Suppurative Clinical Response (HiSCR)

Nothera® (droxidopa) for the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about the black out” in adult patients with symptomatic neurogenic orthostatic hypotension (2014)

Orthostatic Hypotension Symptom Assessment (OHSA)

Cosentyx® (secukinumab) for moderate to severe plaque psoriasis (2015)

Psoriasis symptom diary (PSD)

Kybella® (deoxycholic acid) for the improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults (2015)

Clinical Reported Submental Fat Rating Scale (CR-SMFRS)
Patient Reported Submental Fat Rating Scale (PR-SMFRS)
Patient Reported Submental Fat Impact Scale (PR-SMFIS)

Jakafi® (ruxolitinib) for myelofibrosis (2011)

Myelofibrosis Symptom Assessment Form version 2.0 diary (MF-SAF v2.0 diary)

Additionally, Adelphi Values in collaboration the Critical Path institute and a consortium of pharmaceutical sponsors led the development and validation of the Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) for the assessment of the severity of core defining asthma symptoms among adolescent (12-17 years) and adult patients. These measures are among the first COAs to be qualified by FDA as part of the Drug Development Tool (DDT) Qualification Program.