Critical Path Institute

CRITICAL PATH PUBLIC PRIVATE PARTNERSHIPS

CRITICAL PATH INSTITUTE

ADVANCING STANDARDS AND METHODOLOGIES TO GENERATE REAL WORLD EVIDENCE FROM REAL WORLD DATA THROUGH A NEONATAL PILOT PROJECT

ARIZONA CENTER FOR EDUCATION AND RESEARCH ON THERAPEUTICS

STRENGTHEINING THE OPERATING FRAMEWORK AND FURTHERING THE OBJECTIVES OF CFAST

ESTABLISHMENT OF A RARE DISEASE CLINICAL OUTCOME ASSESSMENT CONSORTIUM

COLLABORATIVE CARDIOVASCULAR DRUG SAFETY AND BIOMARKER RESEARCH PROGRAM

COLLABORATIVE DRUG SAFETY TESTING RESEARCH

DEVELOPMENT OF A QUALIFICATION PLAN FOR THE VIRTUAL REALITY FUNCTIONAL CAPACITY ASSESSMENT TOOL - SHORT LIST (VRFCAT-SLX) (DDT COA #000004) - ABSTRACT NEARLY 7 MILLION PEOPLE IN THE UNITED STATES ARE LIVING WITH ALZHEIMER’S DISEASE (AD). AS PEOPLE WITH AD PROGRESS THROUGH THE STAGES OF THIS DISEASE, THEIR ABILITY TO FUNCTION INDEPENDENTLY AND CARRY OUT ACTIVITIES OF DAILY LIVING (E.G., HOUSEHOLD CHORES AND PERSONAL CARE) DECREASES DUE TO COGNITIVE IMPAIRMENT PROGRESSING TO DEMENTIA, LEADING TO INCREASED BURDEN ON CAREGIVERS AND THE US HEALTHCARE SYSTEM. HOWEVER, A PSYCHOMETRICALLY SOUND, PUBLICLY AVAILABLE MEASURE OF COGNITION-DEPENDENT DAY-TO-DAY FUNCTIONING FOR PERSONS WITH AD HAS NOT BEEN RECOGNIZED BY FDA AS FIT-FOR-PURPOSE FOR USE IN EARLY-STAGE AD DRUG DEVELOPMENT. WE PROPOSE THE PREPARATION AND SUBMISSION OF A QUALIFICATION PLAN (QP) TO SUPPORT THE QUALIFICATION OF THE VIRTUAL REALITY FUNCTIONAL CAPACITY ASSESSMENT TOOL-SHORT LIST (VRFCAT-SLX) AS A PERFORMANCE OUTCOME (PERFO) MEASURE OF COGNITION-DEPENDENT DAY-TO-DAY FUNCTIONING IN PEOPLE DIAGNOSED WITH BIOMARKER-POSITIVE, CLINICAL STAGES 2 AND 3 AD. A MEASURE OF DAY-TO-DAY FUNCTIONING WAS ACCEPTED INTO THE CENTER FOR DRUG EVALUATION AND RESEARCH’S (CDER’S) CLINICAL OUTCOME ASSESSMENT (COA) QUALIFICATION PROGRAM UNDER DDT #000004 ON OCTOBER 12, 2016. THE PRO CONSORTIUM’S COGNITION WORKING GROUP SELECTED THE VRFCAT-SLX AS THE MEASURE FOR QUALIFICATION AS IT HAS HAS QUALITATIVE EVIDENCE SUPPORTING ITS CONTENT VALIDITY. A CONFIRMATORY QUALITATIVE STUDY IS UNDERWAY IN PEOPLE WITH BIOMARKER-POSITIVE, CLINICAL STAGES 2 AND 3 AD. NEXT, A QUANTITATIVE EVIDENCE STRATEGY WILL BE PREPARED, SUPPORTED BY A STUDY PROTOCOL AND STATISTICAL ANALYSIS PLAN (SAP) USED TO DEVELOP A QUALIFICATION PLAN (QP). THE NEXT STEP IN THE QUALIFICATION PROCESS WILL BE SUBMISSION OF THE QP TO FDA TO SUPPORT QUALIFICATION OF THE VRFCAT-SLX FOR USE IN AD DRUG DEVELOPMENT. OUR APPROACH INCLUDES 4 AIMS. FOR AIM 1, WE WILL CONVENE AN ADVISORY PANEL OF CLINICIANS AND PATIENT PARTICIPANTS TO PROVIDE RECOMMENDATIONS ON STUDY DESIGN TO INCREASE THE FEASIBILITY OF OUR PROPOSED STRATEGY AND TO REVIEW THE STUDY PROTOCOL AND OTHER STUDY DOCUMENTS. FOR AIM 2, WE WILL PREPARE A DESCRIPTION OF THE PROPOSED QUANTITATIVE EVIDENCE GENERATION STRATEGY (INCLUDING DEVELOPMENT OF A PROTOCOL AND SAP) DESIGNED TO ASSESS THE VRFCAT-SLX’S MEASUREMENT PROPERTIES. FOR AIM 3, WE WILL DEVELOP THE QP BY COMPILING THE EVIDENCE FROM LITERATURE AND QUALITATIVE DATA FROM TWO COGNITIVE INTERVIEW STUDIES AND USING THE PROTOCOL AND SAP TO COMPLETE THE RELEVANT SECTIONS OF THE QP, FOLLOWING FDA’S COA QP CONTENT OUTLINE. AIM 4 WILL INVOLVE COMPILING AND SUBMITTING THE QP WITH ALL NECESSARY APPENDICES AND ATTACHMENTS. THE GOAL OF THIS PROJECT WILL BE A PUBLICLY AVAILABLE PERFO MEASURE FOR ASSESSING COGNITION-DEPENDENT DAY-TO-DAY FUNCTIONING IN CLINICAL TRIALS FOR PEOPLE WITH BIOMARKER-POSITIVE, CLINICAL STAGE 2 AND 3 AD. QUALIFYING THE VRFCAT-SLX WILL FILL A CRITICAL GAP IN THE MEASUREMENT OF DAY-TO-DAY FUNCTIONING IN AD TREATMENT TRIALS.

PSYCHOMETRIC ANALYSES AND QUANTITATIVE STUDY REPORT FOR QUALIFICATION OF THE CHRONIC HEART FAILURE SYMPTOM SCALE (CHF-SS) (DDT COA #000112) - ABSTRACT HEART FAILURE IS A MAJOR WORLDWIDE HEALTH PROBLEM, WITH A PREVALENCE OF OVER 6.2 MILLION IN THE UNITED STATES (US), AND OVER 26 MILLION WORLDWIDE. HEART FAILURE IS ASSOCIATED WITH SIGNS AND SYMPTOMS SUCH AS BREATHLESSNESS WITH EXERTION, SHORTNESS OF BREATH, FATIGUE, TIREDNESS OR WEAKNESS, DIFFICULTY BREATHING WHEN LYING DOWN, SLEEPING PROBLEMS, SWOLLEN LEGS OR ANKLES, AND WEIGHT GAIN, WHICH CAN NEGATIVELY IMPACT HEALTH-RELATED QUALITY OF LIFE AND PHYSICAL FUNCTION. ALTHOUGH MULTIPLE CLINICAL OUTCOME ASSESSMENTS (COAS), SPECIFICALLY PATIENT-REPORTED OUTCOME (PRO) MEASURES, HAVE BEEN DEVELOPED TO ASSESS HEART FAILURE SYMPTOMS, TESTED AGAINST THE SCIENTIFIC PROCESSES OF THEIR TIME, AND WIDELY USED IN EVALUATING HEART FAILURE INTERVENTIONS, THEY EACH PRESENT THEIR OWN LIMITATIONS WITH RESPECT TO RECENT US FOOD AND DRUG ADMINISTRATION (FDA) COA-RELATED GUIDANCES. A NEW MEASURE OF CHF SYMPTOM SEVERITY WAS ACCEPTED INTO THE CENTER FOR DRUG EVALUATION AND RESEARCH’S (CDER’S) COA QUALIFICATION PROGRAM UNDER DDT #000112 ON MAY 3, 2019. AS REQUESTED BY FDA IN THE LETTER OF INTENT RESPONSE, A QUALIFICATION PLAN (QP) WAS PREPARED AND SUBMITTED TO FDA ON MARCH 24, 2023, THAT DOCUMENTS THE DEVELOPMENT OF AND CONTENT VALIDITY EVIDENCE SUPPORTING THE CHF-SS, ALONG WITH THE CHF WORKING GROUP’S RESEARCH PLAN FOR OBTAINING THE QUANTITATIVE EVIDENCE NECESSARY TO SUPPORT QUALIFICATION OF THE MEASURE FOR A LIMITED CONTEXT OF USE IN CHF DRUG DEVELOPMENT. A REVIEWABILITY ASSESSMENT MEMO WAS SUBSEQUENTLY RECEIVED, INDICATING THAT THE QP WAS DETERMINED TO BE REVIEWABLE BY FDA ON OCTOBER 2, 2023. AN AMENDED STATISTICAL ANALYSIS PLAN (SAP) WAS SUBMITTED TO FDA ON MARCH 20, 2024, TO REFLECT THE EVOLUTION IN OUR APPROACH TO THESE ANALYSES IN LIGHT OF RECENT FDA FEEDBACK ON OTHER QUALIFICATION SUBMISSIONS AND CURRENT THINKING REGARDING THE BEST PRACTICES IN OUR FIELD. ONCE FDA FEEDBACK ON THE QP IS RECEIVED, ADDITIONAL MODIFICATIONS TO THE SAP MAY BE NECESSARY. OUR APPLICATION INCLUDES 3 AIMS. FOR AIM 1, WE WILL FINALIZE THE SAP FOR CROSS-SECTIONAL ANALYSES IN RESPONSE TO FDA FEEDBACK. FOR AIM 2, WE WILL ANALYZE THE AVAILABLE CROSS-SECTIONAL DATASET CONTAINING CHF-SS DATA, IN ACCORDANCE WITH THE QP AND THE FINAL SAP INCORPORATING FDA FEEDBACK. FOR AIM 3, WE WILL PREPARE A QUANTITATIVE STUDY REPORT FOR THE CHF-SS FOR FUTURE SUBMISSION WITH THE CHF-SS FULL QUALIFICATION PACKAGE. THE LONG-TERM RESULT OF THIS PROJECT WILL BE TO QUALIFY THE CHF-SS FOR THE ASSESSMENT OF SYMPTOM SEVERITY IN CHF TREATMENT TRIALS ACCORDING TO THE MOST RECENT, RIGOROUS STANDARDS AND BEST PRACTICES TO DEVELOP FIT-FOR-PURPOSE COAS FOR REGULATORY DECISION MAKING.

THERAPEUTIC AREA DATA STANDARD FOR CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA

IMPROVED DATA STANDARDS FOR ANIMAL EFFICACY STUDIES AND NATURAL HISTORY STUDIES FOR ANIMAL RULE APPLICATIONS

THERAPEUTIC AREA DATA STANDARD FOR TREATMENT OF HIV

PSYCHOMETRIC ANALYSES AND QUANTITATIVE STUDY REPORT FOR QUALIFICATION OF THE PEDIATRIC ASTHMA DIARY-CHILD (PAD-C) AND THE PEDIATRIC ASTHMA DIARY-OBSERVER (PAD-O) (DDT COA #000099) - ABSTRACT ASTHMA IS ONE OF THE MOST COMMON CHILDHOOD CHRONIC CONDITIONS WORLDWIDE. IN THE UNITED STATES (US), ASTHMA PRESENTS IN 8.3% OF CHILDREN UNDER 18 YEARS OF AGE AND 9.5% OF CHILDREN BETWEEN THE AGES OF 5 THROUGH 11. FOR U.S. CHILDREN, ASTHMA IS ONE OF THE LEADING CAUSES OF SCHOOL ABSENTEEISM AND THE THIRD RANKING CAUSE OF HOSPITALIZATION. DEVELOPMENT OF BETTER TREATMENTS FOR CHILDREN UNDER 12 YEARS OLD IS NEEDED TO IMPROVE SYMPTOM CONTROL AND REDUCE THESE BURDENS. PEDIATRIC ASTHMA CLINICAL TRIALS FACE CHALLENGES DUE TO THE POOR RELIABILITY OF THE TRADITIONAL ENDPOINT BASED ON LUNG FUNCTION ASSESSMENT IN YOUNG CHILDREN, HIGHLIGHTING A NEED FOR NOVEL METHODS FOR TRIALS IN CHILDREN UNDER 12 YEARS OLD. TO ASSESS CLINICAL BENEFIT, A POSITIVE EFFECT OF A TREATMENT ON HOW CHILDREN WITH ASTHMA FEEL AND FUNCTION, CLINICAL OUTCOME ASSESSMENTS (COAS) FOR SELF-REPORT (PATIENT- REPORTED OUTCOME [PRO] MEASURES) AS WELL AS OBSERVER REPORT FOR CHILDREN UNDER AGE 8 NEED TO BE DEVELOPED FOLLOWING RIGOROUS PATIENT-FOCUSED DRUG DEVELOPMENT APPROACHES SPECIFICALLY TO SUPPORT ENDPOINTS IN PEDIATRIC ASTHMA CLINICAL TRIALS. THE CENTER FOR DRUG EVALUATION AND RESEARCH’S (CDER’S) COA QUALIFICATION PROGRAM ACCEPTED A LETTER OF INTENT (LOI) TO QUALIFY THE PEDIATRIC ASTHMA DIARY-CHILD (PAD-C) AND THE PEDIATRIC ASTHMA DIARY-OBSERVER (PAD-O) TO ASSESS SEVERITY OF ASTHMA SYMPTOMS AND SIGNS UNDER DDT #000099 ON JUNE 9, 2017. A QUALIFICATION PLAN (QP) WAS PREPARED AND SUBMITTED TO FDA ON DECEMBER 15, 2022. THE QP INCLUDES THE PEDIATRIC ASTHMA WORKING GROUP’S RESEARCH PLAN FOR OBTAINING THE QUANTITATIVE EVIDENCE NECESSARY TO SUPPORT QUALIFICATION OF THE MEASURES FOR A LIMITED CONTEXT OF USE IN PEDIATRIC ASTHMA DRUG DEVELOPMENT. THE QP DETERMINATION LETTER WAS RECEIVED ON NOVEMBER 22, 2023, INDICATING THAT THE QP HAD BEEN ACCEPTED. IT INCLUDED A REQUEST FOR SIGNIFICANT REVISIONS TO THE STATISTICAL ANALYSIS PLAN (SAP). A SAP, VERSION 2.0, WAS SUBMITTED FOR FDA REVIEW AND CONFIRMATION ON APRIL 15, 2025, ADDRESSING THE CONCERNS RAISED IN THE QP DETERMINATION LETTER AND INCLUDING MODIFICATIONS TO REFLECT BEST PRACTICES IN OUR FIELD SINCE THE SAP WAS ORIGINALLY PREPARED IN 2022. ONCE FDA FEEDBACK ON THE QP IS RECEIVED, ADDITIONAL MODIFICATIONS TO THE SAP MAY BE NECESSARY AND ANALYSES CAN PROCEED. OUR APPLICATION INCLUDES 4 AIMS. FOR AIM 1, WE WILL FINALIZE THE SAP FOR CROSS-SECTIONAL ANALYSES IN RESPONSE TO FDA FEEDBACK. FOR AIM 2, WE WILL CONDUCT MISSING DATA SIMULATION ANALYSES PER THE FINALIZED SAP. FOR AIM 3, WE WILL REVIEW PAD-C AND PAD-O QUANTITATIVE ANALYSIS RESULTS TO ENSURE THEY REFLECT THE ANALYSES PROPOSED IN THE FINALIZED SAP, ARE OF HIGH QUALITY, AND CAN BE USED TO DRAW ACTIONABLE CONCLUSIONS. FOR AIM 4, WE WILL REVIEW AND REVISE A QUANTITATIVE STUDY REPORT DOCUMENTING THE PAD-C AND PAD-O QUANTITATIVE PILOT STUDY METHODS, RESULTS, AND INTERPRETATION FOR FUTURE SUBMISSION WITH THE PAD-C AND PAD-O FULL QUALIFICATION PACKAGE. THE LONG-TERM RESULT OF THIS PROJECT WILL BE TO QUALIFY THE PAD-C AND PAD-O FOR THE ASSESSMENT OF SYMPTOM AND SIGN SEVERITY IN PEDIATRIC ASTHMA TREATMENT TRIALS, ACCORDING TO THE MOST RECENT, RIGOROUS STANDARDS AND BEST PRACTICES TO DEVELOP FIT-FOR-PURPOSE COAS FOR REGULATORY DECISION MAKING.

DEVELOPMENT OF A FULL QUALIFICATION PACKAGE FOR THE PROMIS SHORT FORM V1.0?FATIGUE-MULTIPLE SCLEROSIS 8A (DDT COA #000069) - ABSTRACT OVER 1 MILLION PEOPLE IN THE UNITED STATES ARE LIVING WITH MULTIPLE SCLEROSIS (MS), AND THE MAJORITY OF PEOPLE WITH MS ARE LIKELY TO EXPERIENCE SEVERE, DEBILITATING FATIGUE AT SOME POINT. HOWEVER, A PSYCHOMETRICALLY SOUND, PUBLICLY AVAILABLE MEASURE OF FATIGUE SEVERITY OPTIMIZED FOR PERSONS WITH MS FROM THE PATIENT PERSPECTIVE HAS NOT YET BEEN RECOGNIZED BY FDA AS FIT-FOR-PURPOSE FOR USE IN DRUG DEVELOPMENT. WE PROPOSE THE PREPARATION AND SUBMISSION OF A FULL QUALIFICATION PACKAGE (FQP) TO SUPPORT THE QUALIFICATION OF THE PROMIS SHORT FORM V1.0—FATIGUE-MULTIPLE SCLEROSIS 8A (PROMIS FATIGUEMS—8A) AS A PATIENT-REPORTED OUTCOME (PRO) MEASURE OF FATIGUE SEVERITY IN INDIVIDUALS DIAGNOSED WITH ALL FORMS OF MS. A MEASURE OF FATIGUE SEVERITY WAS ACCEPTED INTO THE CENTER FOR DRUG EVALUATION AND RESEARCH’S (CDER’S) CLINICAL OUTCOME ASSESSMENT (COA) QUALIFICATION PROGRAM UNDER DDT #000069 ON JUNE 21, 2017. THE PRO CONSORTIUM’S MS WORKING GROUP SELECTED THE PROMIS FATIGUEMS— 8A AS THE FATIGUE MEASURE FOR QUALIFICATION AS IT HAS BEEN OPTIMIZED FOR USE IN PERSONS WITH MS. AT FDA’S REQUEST, AN INITIAL BRIEFING PACKAGE WAS SUBMITTED ON OCTOBER 18, 2019, DOCUMENTING THE DEVELOPMENT OF AND CONTENT VALIDITY EVIDENCE SUPPORTING THE PROMIS FATIGUEMS—8A. NEXT, A QUALIFICATION PLAN (QP) WAS SUBMITTED TO FDA ON AUGUST 31, 2020; REVISED VERSIONS WERE RESUBMITTED ON MAY 7, 2021, AND NOVEMBER 15, 2021. THE QP ADDRESSED THE MS WORKING GROUP’S RESEARCH PLAN FOR OBTAINING THE QUANTITATIVE EVIDENCE TO SUPPORT QUALIFICATION OF THE MEASURE. AFTER FDA ACCEPTS THE QP, THE NEXT STEPS WILL BE TO ANALYZE CROSS-SECTIONAL AND LONGITUDINAL DATASETS TO GENERATE QUANTITATIVE EVIDENCE AND TO PREPARE AND SUBMIT AN FQP. OUR APPROACH INCLUDES 3 AIMS. FOR AIM 1, WE WILL ANALYZE AVAILABLE CROSS-SECTIONAL AND LONGITUDINAL DATASETS CONTAINING THE PROMIS FATIGUEMS—8A IN ACCORDANCE WITH THE ACCEPTED QP AND REVISED STATISTICAL ANALYSIS PLAN TO DOCUMENT ITS VALIDITY, RELIABILITY, AND RESPONSIVENESS AS AN OUTCOME MEASURE IN PEOPLE WITH ALL FORMS OF MS. FOR AIM 2, WE WILL PREPARE AN FQP FOR THE PROMIS FATIGUEMS—8A USING THE CDER COA FQP CONTENT OUTLINE AND INTEGRATE ALL EVIDENCE SUPPORTING THE MEASURE, INCLUDING RESULTS OF THE COMPLETED QUALITATIVE AND QUANTITATIVE RESEARCH. AIM 3 WILL INVOLVE THE SUBMISSION OF THE FQP WITH ALL NECESSARY APPENDICES AND ATTACHMENTS, INCLUDING A USER MANUAL AND THE ASSOCIATED ANALYTIC DATASETS AND PROGRAMMING CODE. THE GOAL OF THIS PROJECT WILL BE A PUBLICLY AVAILABLE AND ACCESSIBLE PRO MEASURE FOR ASSESSING FATIGUE SEVERITY IN MS CLINICAL TRIALS FOR PEOPLE WITH ALL FORMS OF MS. AS SUCH, QUALIFYING THE PROMIS FATIGUEMS—8A WILL FILL A CRITICAL GAP IN THE MEASUREMENT OF FATIGUE SEVERITY IN MS TREATMENT TRIALS.

PREPARATION AND SUBMISSION SUPPORT OF A FULL QUALIFICATION PACKAGE (FQP) FOR THE DIARY FOR IRRITABLE BOWEL SYNDROME SYMPTOMS—DIARRHEA (DIBSS-D) (DDT #000148) - ABSTRACT IRRITABLE BOWEL SYNDROME (IBS) IS A CHRONIC, OFTENTIMES DISABLING GASTROINTESTINAL DISORDER CHARACTERIZED BY RECURRENT ABDOMINAL PAIN ASSOCIATED WITH ALTERATIONS IN BOWEL HABITS (DIARRHEA AND/OR CONSTIPATION). THREE SUBTYPES OF IBS HAVE BEEN DEFINED BASED ON STOOL PATTERNS: IBS WITH PREDOMINANT DIARRHEA (IBS-D), IBS WITH PREDOMINANT CONSTIPATION (IBS-C), AND ALTERNATING OR MIXED IBS (IBS-M). APPROXIMATELY 10% TO 15% OF ADULTS IN THE UNITED STATES ARE AFFECTED BY IBS, WITH IBS-D ESTIMATED TO ACCOUNT FOR ROUGHLY A THIRD OF THE CASES. DUE TO THE DISRUPTIVENESS OF THE ABDOMINAL AND BOWEL MOVEMENT-RELATED SYMPTOMS IN THEIR DAILY LIVES, IBS IS AMONG THE TOP 10 REASONS PEOPLE CONSULT A PRIMARY CARE PHYSICIAN. ALTHOUGH SEVERAL GLOBAL AND SYMPTOM-SPECIFIC PRO MEASURES HAVE BEEN USED TO SUPPORT APPROVAL OF TREATMENTS FOR IBS, FDA ENCOURAGED THE DEVELOPMENT OF COMPREHENSIVE SUBTYPE- SPECIFIC SYMPTOM SEVERITY MEASURES THAT MEET ITS REGULATORY EXPECTATIONS. THE PRO CONSORTIUM FORMED THE IBS WORKING GROUP TO MEET THIS UNMET MEASUREMENT NEED. TO BEGIN THE DEVELOPMENT OF THE DIARY FOR IRRITABLE BOWEL SYNDROME SYMPTOMS–DIARRHEA (DIBSS-D) AND MEASURES FOR THE 2 OTHER SUBTYPES, THE IBS WORKING GROUP REVIEWED THE LITERATURE AND CONDUCTED CONCEPT ELICITATION INTERVIEWS TO IDENTIFY A COMPREHENSIVE SET OF SYMPTOMS EXPERIENCED BY PEOPLE WITH IBS. BASED ON THESE RESULTS AND INPUT FROM A PATIENT REPRESENTATIVE AND ADVISORY PANELISTS, A SET OF IBS SYMPTOMS WAS IDENTIFIED, AND DRAFT ITEMS WERE GENERATED TO ASSESS THE CORE SYMPTOMS OF EACH SUBTYPE. THEN, 3 ROUNDS OF COGNITIVE INTERVIEWS WERE CONDUCTED WITH 16 PARTICIPANTS WITH IBS-D TO ENSURE THAT THE DIBSS-D ADDRESSED THE IBS SYMPTOMS OF GREATEST IMPORTANCE TO PARTICIPANTS AND TO OPTIMIZE THE ITEM WORDING AND RESPONSE SCALES. THE DEVELOPMENTAL DIBSS-D WAS SUBSEQUENTLY TESTED IN A CROSS-SECTIONAL OBSERVATIONAL STUDY CONDUCTED AT 10 CLINICAL SITES ACROSS THE US THAT INCLUDED 133 PARTICIPANTS WITH IBS-D. AIM 1 OF THIS PROPOSED PROJECT IS TO ANALYZE THE DATA COLLECTED FROM PARTICIPANTS WITH IBS-D IN OUR CROSS-SECTIONAL OBSERVATIONAL STUDY IN ACCORDANCE WITH THE QP AND ITS ACCOMPANYING STATISTICAL ANALYSIS PLAN CURRENTLY UNDER QRT REVIEW. AIM 2 IS TO PREPARE A FULL QUALIFICATION PACKAGE (FQP) IN ACCORDANCE WITH THE MOST CURRENT VERSION OF FDA’S COA FQP CONTENT OUTLINE, AND AIM 3 IS TO SUBMIT THE DIBSS-D FQP TO FDA. THE INTENDED RESULT OF THIS PROJECT WILL BE A QUALIFIED, PUBLICLY AVAILABLE PRO MEASURE FOR THE ASSESSMENT OF ABDOMINAL AND BOWEL- MOVEMENT-RELATED SYMPTOM SEVERITY IN PERSONS WITH IBS-D. QUALIFYING THE DIBSS-D WILL FILL A CRITICAL GAP IN THE MEASUREMENT OF PATIENT-REPORTED CLINICAL BENEFIT IN IBS-D TREATMENT TRIALS.

DEVELOPMENT OF A FULL QUALIFICATION PACKAGE (FQP) FOR THE PROMISNQ SHORT FORM V2.0 - PHYSICAL FUNCTION - MULTIPLE SCLEROSIS 15A (DDT COA #000123) - ABSTRACT OVER 1 MILLION PEOPLE IN THE UNITED STATES ARE LIVING WITH MULTIPLE SCLEROSIS (MS), A DISEASE THAT HAS SIGNIFICANT IMPACTS ON PHYSICAL FUNCTIONING AND, CONSEQUENTLY, HEALTH-RELATED QUALITY OF LIFE. HOWEVER, A PSYCHOMETRICALLY SOUND, PUBLICLY AVAILABLE MEASURE OF PHYSICAL FUNCTION OPTIMIZED FOR PERSONS WITH MS DEVELOPED FROM THE PATIENT PERSPECTIVE HAS NOT BEEN RECOGNIZED BY FDA AS FIT- FOR-PURPOSE FOR USE IN DRUG DEVELOPMENT. WE PROPOSE THE PREPARATION AND SUBMISSION OF A FULL QUALIFICATION PACKAGE (FQP) TO SUPPORT THE QUALIFICATION OF THE PROMIS / QUALITY OF LIFE IN NEUROLOGICAL DISORDERS™ (NEURO-QOL™) PHYSICAL FUNCTION MEASURE FOR MULTIPLE SCLEROSIS (PROMISNQ PFMS—15A) AS A PATIENT-REPORTED OUTCOME (PRO) MEASURE OF PHYSICAL FUNCTION IN PEOPLE DIAGNOSED WITH ALL FORMS OF MS. A MEASURE OF PHYSICAL FUNCTION WAS ACCEPTED INTO THE CENTER FOR DRUG EVALUATION AND RESEARCH’S (CDER’S) CLINICAL OUTCOME ASSESSMENT (COA) QUALIFICATION PROGRAM UNDER DDT #000123 ON JUNE 21, 2017. THE PRO CONSORTIUM’S MS WORKING GROUP SELECTED THE PROMISNQ PFMS—15A AS THE PHYSICAL FUNCTION MEASURE FOR QUALIFICATION AS IT HAS BEEN OPTIMIZED FOR USE IN PERSONS WITH MS AND HAS QUALITATIVE EVIDENCE SUPPORTING ITS CONTENT VALIDITY. NEXT, A QUALIFICATION PLAN (QP) WAS SUBMITTED TO FDA ON NOVEMBER 29, 2021. THE QP ADDRESSED THE WORKING GROUP’S RESEARCH PLAN FOR OBTAINING QUANTITATIVE EVIDENCE TO SUPPORT QUALIFICATION OF THE MEASURE. AFTER FDA ACCEPTANCE OF THE QP, THE NEXT STEPS WILL BE TO ANALYZE CROSS-SECTIONAL AND LONGITUDINAL DATASETS FROM THE UNITED KINGDOM MS REGISTER STUDY AND THE UNIVERSITY OF WASHINGTON MS PSYCHOMETRIC EVALUATION STUDY TO GENERATE QUANTITATIVE EVIDENCE AND TO PREPARE AND SUBMIT AN FQP. OUR APPROACH INCLUDES 3 AIMS. FOR AIM 1, WE WILL ANALYZE AVAILABLE CROSS-SECTIONAL AND LONGITUDINAL DATASETS THAT INCLUDE THE PROMISNQ PFMS—15A IN ACCORDANCE WITH THE ACCEPTED QP AND STATISTICAL ANALYSIS PLAN TO DOCUMENT ITS VALIDITY, RELIABILITY, AND RESPONSIVENESS AS AN OUTCOME MEASURE IN PEOPLE WITH ALL FORMS OF MS. FOR AIM 2, WE WILL PREPARE AN FQP FOR THE PROMISNQ PFMS—15A USING THE CDER COA FQP CONTENT OUTLINE AND INTEGRATE ALL EVIDENCE SUPPORTING THE MEASURE, INCLUDING RESULTS OF THE COMPLETED QUALITATIVE AND QUANTITATIVE RESEARCH. AIM 3 WILL INVOLVE THE SUBMISSION OF THE FQP WITH ALL NECESSARY APPENDICES AND ATTACHMENTS, INCLUDING A USER MANUAL AND THE ASSOCIATED ANALYSIS DATASETS AND PROGRAMMING CODE. THE GOAL OF THIS PROJECT WILL BE A PUBLICLY AVAILABLE AND ACCESSIBLE PRO MEASURE FOR ASSESSING PHYSICAL FUNCTION IN MS CLINICAL TRIALS FOR PEOPLE WITH ALL FORMS OF MS. AS SUCH, QUALIFYING THE PROMISNQ PFMS—15A WILL FILL A CRITICAL GAP IN THE MEASUREMENT OF PHYSICAL FUNCTION IN MS TREATMENT TRIALS.

DEVELOPMENT OF A QUALIFICATION PLAN FOR AN ACTIVITY MONITOR-BASED ENDPOINT MEASURE IN CHRONIC HEART FAILURE (DDT COA #000114) - ABSTRACT CHRONIC HEART FAILURE (CHF) RESULTS WHEN THE HEART CANNOT PUMP ENOUGH BLOOD TO MEET THE BODY’S NEEDS. APPROXIMATELY 6.5 MILLION PEOPLE IN THE UNITED STATES AND 26 MILLION PEOPLE WORLDWIDE HAVE HEART FAILURE. SPECIFIC CHF SYMPTOMS, SUCH AS SHORTNESS OF BREATH, CHEST PAIN, AND FATIGUE, ARE CONTRIBUTING FACTORS TO REDUCED ACTIVITY AND LIMITATIONS IN ABILITY TO PERFORM DAILY ACTIVITIES. HENCE, IN CONJUNCTION WITH THE ASSESSMENT OF PATIENT-REPORTED SYMPTOMS AND IMPACTS OF CHF, REGULATORS AND SPONSORS HAVE EXPRESSED INTEREST IN NOVEL MEASURES OF DAILY ACTIVITY THAT LEVERAGE WEARABLE DEVICES. TO HELP ADDRESS THIS MEASUREMENT OPPORTUNITY, THE CHF WORKING GROUP’S PROPOSED ACTIVITY MONITOR-BASED ENDPOINT MEASURE WAS ACCEPTED INTO THE CENTER FOR DRUG EVALUATION AND RESEARCH’S COA QUALIFICATION PROGRAM (DDT #000114) ON MAY 3, 2019. IT IS INTENDED TO ASSESS ASPECTS OF OBJECTIVELY MEASURED PHYSICAL ACTIVITY THAT REFLECT A PERSON WITH CHF’S ABILITY TO PERFORM MEANINGFUL DAILY ACTIVITIES. TO FURTHER THIS QUALIFICATION EFFORT, THE PROPOSED PROJECT WILL RESULT IN THE DEVELOPMENT AND SUBMISSION OF A QUALIFICATION PLAN (QP). A CONCEPT ELICITATION STUDY WAS CONDUCTED TO GENERATE QUALITATIVE EVIDENCE REGARDING THE DAY-TO- DAY PHYSICAL ACTIVITIES THAT BRING PURPOSE AND MEANING TO THE LIVES OF PERSONS WITH CHF. ACTIVITIES FREQUENTLY REPORTED INVOLVED LIGHT TO MODERATE PHYSICAL ACTIVITY (E.G., CLEANING, COOKING, DOING LAUNDRY, AND GARDENING) AND WALKING (E.G., SHOPPING AND GOING TO APPOINTMENTS). THE NEXT STEP WILL BE TO FORM AN ADVISORY PANEL, COMPOSED OF INDIVIDUALS WITH EXPERTISE IN THE IDENTIFICATION OF CLINICALLY MEANINGFUL ACTIVITY MONITOR-BASED OUTCOMES, TO REVIEW THE QUALITATIVE STUDY FINDINGS AND GAIN CONSENSUS ON THE EXISTING (OR PROPOSED NOVEL) ACTIVITY MONITOR METRIC(S) THAT BEST REFLECT/CAPTURE THE MEANINGFUL ASPECT OF HEALTH REPRESENTED BY THESE ACTIVITIES. ONCE THERE IS AGREEMENT ON THE SPECIFIC ACTIVITY MONITOR-BASED METRIC(S) TO BE EVALUATED FURTHER, WE WILL PROCEED WITH DEVELOPMENT OF THE QP. THE COMPILED QP WILL ADDRESS THE CHF WORKING GROUP’S RESEARCH PLAN FOR GENERATING THE QUANTITATIVE EVIDENCE NECESSARY TO SUPPORT QUALIFICATION OF THE ACTIVITY MONITOR-BASED ENDPOINT MEASURE FOR USE IN CHF DRUG DEVELOPMENT. OUR APPROACH INCLUDES TWO AIMS: (1) CONVENE AN ADVISORY PANEL TO PROVIDE CRITICAL INPUT REGARDING THE RESULTS OF THE QUALITATIVE STUDY AND GAIN CONSENSUS ON THE SPECIFIC ACTIVITY MONITOR METRIC(S) THAT WILL BE THE FOCUS OF THE QP, AND (2) PREPARE AND SUBMIT A QP FOR THE ACTIVITY MONITOR-BASED ENDPOINT MEASURE. THE LONG-TERM RESULT OF THIS PROJECT WILL BE A QUALIFIED, PUBLICLY AVAILABLE ACTIVITY MONITOR-BASED ENDPOINT MEASURE, WHICH WILL FILL A CRITICAL GAP IN THE ASSESSMENT OF PHYSICAL ACTIVITY IN CHF TREATMENT TRIALS FOR EMERGING INNOVATIVE THERAPIES.

DEVELOPMENT OF A QUALIFICATION PLAN FOR THE PROMIS SHORT FORM V2.1?PHYSICAL FUNCTION-MULTIPLE SCLEROSIS 15A (DDT COA #000123)

DEVELOPMENT OF A QUALIFICATION PLAN FOR THE SYMPTOMS OF MAJOR DEPRESSIVE DISORDER MOMENTARY ASSESSMENT (DDT COA #000109)

PRELIMINARY RESEARCH TO SUPPORT QUALIFICATION OF AN ACTIVITY MONITOR-BASED ENDPOINT MEASURE TO EVALUATE PHYSICAL ACTIVITY IN PERSONS WITH CHRONIC HEART FAILURE FOR DDT COA #114

SAMPLE COLLECTION AND ANALYSIS TO SUPPORT THE QUALIFICATION PLAN FOR DRUG INDUCED SKELETAL MUSCLE INJURY BIOMARKER PANEL FOR DDT-BMQ-000081. - ABSTRACT THIS PROJECT SEEKS TO INCREASE OUR UNDERSTANDING OF THE SENSITIVITY OF THE FOUR PROPOSED SKELETAL MUSCLE INJURY BIOMARKERS TO DETECT DRUG-INDUCED SKELETAL MUSCLE INJURY (DIMI), WHICH WILL ADDRESS AN UNMET NEED IN DRUG DEVELOPMENT FOR DETECTING AND MONITORING DIMI. THE EVIDENCE GENERATED BY THIS PROJECT IS NECESSARY TO SUPPORT THE QUALIFICATION OF FOUR SKELETAL MUSCLE SPECIFIC PROTEINS (SKELETAL TROPONIN I (TNNI2), MYOSIN LIGHT CHAIN 3 (MYL3). FATTY ACID BINDING PROTEIN 3 (FABP3), AND CREATINE KINASE MM (CKM)) AS BIOMARKERS OF SKELETAL MUSCLE INJURY BY THE FOOD AND DRUG ADMINISTRATION’S (FDA’S) BIOMARKER QUALIFICATION PROGRAM (BQP). THIS QUALIFICATION EFFORT IS BEING LED BY THE PREDICTIVE SAFETY TESTING CONSORTIUM’S SKELETAL MUSCLE INJURY WORKING GROUP, FOR WHICH THESE FOUR BIOMARKERS SERVE AS SAFETY BIOMARKERS TO DETECT DIMI WAS ACCEPTED INTO THE BIOMARKER QUALIFICATION PROGRAM. IN ORDER TO PROGRESS TO THE NEXT STAGE OF QUALIFICATION, THE SKELETAL MUSCLE INJURY WORKING GROUP MUST PREPARE A QUALIFICATION PLAN WHICH SUMMARIZES THE PERFORMANCE OF THESE FOUR BIOMARKERS IN THE LEARNING PHASE STUDIES AND PROPOSES THE CONFIRMATORY STUDIES TO SUPPORT THE PROPOSED CONTEXT OF USE UNDER CONSIDERATION BY THE BIOMARKER QUALIFICATION PROGRAM. TO DATE, THE SKELETAL MUSCLE INJURY WORKING GROUP HAS LIMITED CLINICAL DATA IN DIMI OR MUSCLE INJURY POPULATIONS. TO ADDRESS THIS GAP, THE CRITICAL PATH INSTITUTE (C-PATH) PROPOSES THE FOLLOWING RESEARCH AIM. SPECIFIC AIM 1 WILL CONDUCT A STUDY TO DETERMINE THE SENSITIVITY OF THE PROPOSED DRUG-INDUCED MUSCLE INJURY BIOMARKERS (TNNI2, MYL3, FABP3, AND CKM). THE STUDY WILL COLLECT SINGLE SAMPLES FROM 125 SUBJECTS AT THE UNIVERSITY OF MICHIGAN HOSPITAL WITH ADJUDICATED SKELETAL MUSCLE INJURY DUE TO DIMI, SKELETAL MUSCLE INJURY, OR SKELETAL MUSCLE DISEASE AND 125 HEALTHY SUBJECTS. THIS STUDY WILL SUPPORT THE FUTURE SUBMISSION OF A QUALIFICATION PLAN FOR DDT# DDTBMQ000081 BY DEFINING THE SENSITIVITY OF THE PROPOSED DRUG-INDUCED MUSCLE INJURY BIOMARKERS IN MUSCLE INJURY PATIENTS.

SAMPLE COLLECTION AND ANALYSIS TO EXPAND DEMOGRAPHICS DIVERSITY OF REFERENCE RANGE FOR THE FINAL QUALIFICATION PACKAGE FOR GLDH ACTIVITY AS A BIOMARKER OF DRUG INDUCED LIVER INJURY (DDT-BMQ-000050) - ABSTRACT THIS PROJECT SEEKS TO INCREASE OUR UNDERSTANDING OF THE NORMAL REFERENCE RANGE OF GLUTAMATE DEHYDROGENASE (GLDH) IN PEDIATRIC, GERIATRIC, AND EXPANDED ETHNIC NORMAL HEALTHY POPULATIONS, WHICH WILL ADDRESS AN UNMET NEED IN DRUG DEVELOPMENT FOR DETECTING AND MONITORING DRUG-INDUCED LIVER INJURY (DILI). THE EVIDENCE GENERATED BY THIS PROJECT IS NECESSARY TO SUPPORT THE QUALIFICATION OF GLDH BY THE FOOD AND DRUG ADMINISTRATION’S (FDA’S) BIOMARKER QUALIFICATION PROGRAM (BQP). THIS QUALIFICATION EFFORT IS BEING LED BY THE PREDICTIVE SAFETY TESTING CONSORTIUM’S HEPATOTOXICITY WORKING GROUP, FOR WHICH GLDH AS A SAFETY BIOMARKER TO DETECT DILI WAS INTO THE BIOMARKER QUALIFICATION PROGRAM. IN ORDER TO PROGRESS TO THE NEXT STAGE OF QUALIFICATION, THE HEPATOTOXICITY WORKING GROUP MUST PREPARE A FINAL QUALIFICATION PACKAGE WHICH SUMMARIZES THE PERFORMANCE OF GLDH IN THE CONFIRMATORY STUDIES TO SUPPORT THE PROPOSED CONTEXT OF USE UNDER CONSIDERATION BY THE BIOMARKER QUALIFICATION PROGRAM. TO DATE, THE HEPATOTOXICITY WORKING GROUP HAS NOT DEFINED THE NORMAL REFERENCE RANGE OF GLDH IN THESE POPULATIONS, NOR HAS IT BEEN FOUND IN THE PUBLISHED LITERATURE. TO ADDRESS THIS GAP, THE CRITICAL PATH INSTITUTE (C-PATH) PROPOSES THE FOLLOWING RESEARCH AIMS. SPECIFIC AIM 1 WILL CONDUCT A STUDY TO COLLECT SAMPLES FROM HEALTHY INDIVIDUALS SPANNING ADDITIONAL AGE GROUPS UNDER-REPRESENTED IN THE ORIGINAL STUDIES IN 100 NORMAL HEALTHY VOLUNTEERS (BOTH MALE AND FEMALE; 50 PEDIATRIC AND 50 GERIATRIC), FROM THE UNITED STATES (US). THE STUDY WILL COLLECT SINGLE SAMPLES FROM SUBJECTS AT THE UNIVERSITY OF MICHIGAN HOSPITAL FOR ROUTINE VISITS. IN ADDITION, SPECIFIC AIM 2 IS TO CONDUCT A STUDY TO COLLECT SAMPLES FROM HEALTHY INDIVIDUALS TO EXPAND ETHNICITIES UNDER-REPRESENTED IN THE ORIGINAL STUDIES, WHICH WILL SUPPORT THE FUTURE SUBMISSION OF A QUALIFICATION PLAN FOR DDT# DDTBMQ000050 IN ORDER TO FURTHER THE UNDERSTANDING OF GLDH IN VARIOUS POPULATIONS.

QUALIFICATION PLAN PREPARATION TO SUPPORT DDT COA #000069 PROMIS FATIGUE SHORT FORM FOR INDIVIDUALS WITH MULTIPLE SCLEROSIS

C-PATH GLOBAL IMPACT CONFERENCE - ABSTRACT CRITICAL PATH INSTITUTE (C-PATH) IS AN INDEPENDENT, NONPROFIT PUBLIC-PRIVATE PARTNERSHIP (PPP) WITH THE U.S. FOOD AND DRUG ADMINISTRATION (FDA), WITH A MISSION TO IMPROVE THE EFFICIENCY AND SAFETY OF MEDICAL PRODUCT DEVELOPMENT. THE PURPOSE OF THE 4-DAY INTERDISCIPLINARY CONFERENCE, TITLED “C-PATH GLOBAL IMPACT CONFERENCE” IS TO SHOWCASE THE WORK DONE BY SEVERAL C-PATH PUBLIC PRIVATE PARTNERSHIPS (PPPS) IN GENERATING ACTIONABLE SOLUTIONS TO ACCELERATE DRUG DEVELOPMENT. ADDITIONALLY, THIS CONFERENCE WILL FEATURE C-PATH CONSORTIA CURRENT CONTRIBUTIONS TOWARDS THE DEVELOPMENT OF NOVEL THERAPEUTICS FOR CHALLENGING CONDITIONS IN NEUROLOGY, RARE AND ORPHAN CONDITIONS, AND PEDIATRIC POPULATIONS. THIS CONFERENCE WILL BE THE LARGEST AND BROADEST REACHING CONFERENCE ORGANIZED BY C-PATH DURING THE ORGANIZATION’S NEARLY 20-YEAR HISTORY. THE C-PATH GLOBAL IMPACT CONFERENCE WILL BRING TOGETHER AND CAPITALIZE ON THE STRONG EXISTING PRE-COMPETITIVE RELATIONSHIPS BETWEEN C- PATH AND DIVERSE STAKEHOLDERS - INCLUDING REGULATORY AGENCIES (U.S. FOOD AND DRUG ADMINISTRATION [FDA], EUROPEAN MEDICINES AGENCY [EMA], JAPANESE PHARMACEUTICALS AND MEDICAL DEVICES AGENCY [PDMA]), PHARMACEUTICAL INDUSTRIES, ACADEMIC RESEARCHERS, NON-PROFIT ORGANIZATIONS, AND PATIENT GROUPS - TO HOLD PRODUCTIVE DIALOGUE AMONG THE CONFERENCE ATTENDEES AND ADVANCE EFFORTS TO PRODUCE PUBLICLY AVAILABLE DRUG DEVELOPMENT TOOLS TO OPTIMIZE THE EVALUATION OF THE EFFICIENCY AND SAFETY OF NOVEL THERAPEUTICS. THIS CONFERENCE WILL ADVANCE SCIENCE AND CLINICAL PRACTICE THROUGH THE INTERACTIVE DISCUSSIONS BETWEEN STAKEHOLDERS, SUCH AS INDUSTRY, ACADEMIA, REGULATORY AGENCIES, AND PATIENT GROUPS. BY SPURRING FURTHER PRODUCTIVE DIALOGUE REGARDING DATA SHARING, STANDARDIZING METHODOLOGIES, AND THE GENERATION OF ACTIONABLE SOLUTIONS FOR DRUG DEVELOPMENT ACROSS CHALLENGING THERAPEUTIC AREAS, THIS CONFERENCE WILL POSITION C-PATH’S PPPS TO FURTHER ACCELERATE THE DEVELOPMENT AND APPROVAL OF NEW THERAPIES, IMPROVE CLINICAL TRIAL EFFICIENCY, AND ENHANCE PATIENT OUTCOMES.

C-PATH SCIENTIFIC BREAKTHROUGH CONFERENCE: ADDRESSING UNMET NEEDS AND CHALLENGES IN UNDERSERVED DRUG DEVELOPMENT AREAS THROUGH COLLABORATIVE PARTNERSHIPS - ABSTRACT THIS THREE-DAY SCIENTIFIC CONFERENCE; “C-PATH SCIENTIFIC BREAKTHROUGH CONFERENCE: ADDRESSING UNMET NEEDS AND CHALLENGES IN UNDERSERVED DRUG DEVELOPMENT AREAS THROUGH COLLABORATIVE PARTNERSHIPS” WILL BRING TOGETHER REPRESENTATIVES FROM AN INTERDISCIPLINARY TEAM OF INDUSTRY AND ACADEMIC RESEARCHERS, PATIENT GROUPS, AND REGULATORY AGENCIES – TO DISCUSS DRUG DEVELOPMENT CHALLENGES IN NEONATAL MEDICINE, ALPHA-1 ANTITRYPSIN DEFICIENCY (AATD), AND LYSOSOMAL DISEASES (LD), AND BRAINSTORM HOW PRE-COMPETITIVE PUBLIC PRIVATE PARTNERSHIPS (PPPS) CAN HELP ADVANCE DRUG DEVELOPMENT IN THESE UNDERSERVED POPULATIONS. EACH YEAR IN THE U.S., 10% OF NEONATES ARE BORN PRETERM AND THERE IS AN URGENT UNMET NEED TO IMPROVE SURVIVAL AND OUTCOME IN THIS VULNERABLE POPULATION. IN 2015 THE FDA COLLABORATED WITH C-PATH TO CREATE INTERNATIONAL NEONATAL CONSORTIUM (INC), A PPP OF INDUSTRY LEADERS, ACADEMIC RESEARCHERS, REGULATORY AGENCIES, FAMILIES, AND NURSES TO ADVANCE MEDICAL PRODUCT DEVELOPMENT TOOLS FOR ENDORSEMENT BY FDA AND OTHER GLOBAL REGULATORY AGENCIES. AATD IS A CLINICALLY UNDER-RECOGNIZED DISEASE ASSOCIATED WITH AN INCREASED RISK OF CHRONIC LIVER DISEASE IN ADULTS AND CHILDREN AND IS THE LEADING CAUSE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IN ADULTS, OUTSIDE OF SMOKING. UNMET NEEDS IN AATD PERTAIN TO BOTH DIAGNOSIS, EVALUATION, AND TREATMENT OF AATD – FOR BOTH HEPATIC AND PULMONARY MANIFESTATIONS. TO OVERCOME THE LACK OF TOOLS THAT PROVIDE BOTH COMPREHENSIVE AND OBJECTIVE ASSESSMENT OF OUTCOMES IN AATD, THE CRITICAL PATH FOR AATD (CPA-1) HAS INVOLVED STAKEHOLDERS FROM INDUSTRY, ACADEMIA, PATIENT GROUPS, AND REGULATORY AGENCIES, WITH THE OBJECTIVE TO ACHIEVE ACTIONABLE SOLUTIONS OR TOOLS FOR AATD DRUG DEVELOPMENT. LYSOSOMAL DISEASES (LDS) ARE A GROUP OF INHERITED METABOLIC DISORDERS CAUSED BY MUTATIONS IN GENES THAT CODE FOR ENZYMES INVOLVED IN THE BREAKDOWN OF MACROMOLECULES IN LYSOSOMES. CHALLENGES RELATED TO THIS GROUP OF RARE DISEASES RELATE TO EARLY DETECTION, LACK OF EFFECTIVE DIAGNOSTIC TOOLS AND SCREENING PROGRAMS, AND LACK OF EFFECTIVE TREATMENTS. CRITICAL PATH FOR LYSOSOMAL DISEASES (CPLD) IS A PPP COMPRISED OF STAKEHOLDERS FROM PHARMACEUTICAL COMPANIES, ACADEMIC SCIENTISTS WITH AN INTEREST IN LD DRUG DEVELOPMENT, PATIENT GROUPS, AND REGULATORY REPRESENTATIVES. THIS CONFERENCE WILL SHOWCASE THE WORK DONE BY INC, CPA-1, AND CPLD AND CAPITALIZE ON STRONG EXISTING PRE-COMPETITIVE RELATIONSHIPS BETWEEN THE VARIOUS STAKEHOLDERS IN THE DRUG DEVELOPMENT COMMUNITIES TO ADVANCE EFFORTS TO PRODUCE PUBLICLY AVAILABLE DRUG DEVELOPMENT TOOLS AIMING AT IMPROVING THE EFFICIENCY AND SAFETY OF MEDICAL PRODUCT DEVELOPMENT.

CLINICAL/TRANSLATIONAL RESEARCH AWARD FUNDING LEVEL 2 PARTNERING PI OPTION.