Lifetime Impact Study for Achondroplasia (LISA)

Lifetime Impact Study for Achondroplasia (LISA)

Observational study looking at the burden of illness in achondroplasia subjects aged 3 and above. The study will include a 3 year review of historical clinical data as well as a single point collection of questionnaire data to look at the impact on the following in individuals with achondroplasia versus a normative population:

• Quality of life
• Clinical burden
• Healthcare resource use
• Socio-economic burden
• Psychosocial burden

Up to 175 subjects will be enrolled in sites in Argentina, Colombia and Brazil.

Study Overview

• Status: Completed
• Conditions: Achondroplasia

Detailed Description

This is a multinational, epidemiological, observational, retrospective, cross-sectional study of individuals with achondroplasia (subjects). This study will be conducted at up to approximately 4 sites in Latin American Countries - Brazil, Argentina and Colombia.

Subjects will be identified for participation in the study via three routes:

1. During routine hospital visits
2. From clinic lists of those previously treated but no longer followed at the study site.
3. Through collaboration of the Investigator with Achondroplasia patient organizations, other Achondroplasia-related organizations, other healthcare professionals in their country and Achondroplasia-related social media sites. A recruitment flyer will be provided to these organizations, healthcare professionals and distributed to potential subjects.

Data will be collected over a minimum of the three years prior to the date of enrolment. Clinical and healthcare resource use data will be collected from medical records. For each subject enrolled, data from medical records will be collected and entered onto an electronic case report form (eCRF) at each site. Data collection from medical records will be supplemented by records provided by the subject and, if necessary, confirmed by the family Doctor.

Data about QoL, mobility, psychosocial burden, socio-economic burden and healthcare resource use will be collected via a booklet of validated and structured questionnaires.

Characteristics of subjects with achondroplasia (QoL scores, healthcare resource use, educational level, family status, employment status) will be compared with those of the general population, where available.

As this is an observational study, participation will not affect the subject/Investigator relationship, nor influence Investigator's treatment, therapeutic or other management of the subject.

Subject participation onto the study will be voluntary, without financial support to the subject.

• Study Type: Observational
• Enrollment (Actual): 173

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital de Pediatría "Prof. Dr. Juan P. Garrahan"
• Brazil
  • Rio de Janeiro, Brazil
    • Instituto Nacional Fernandes Figueira (IFF), Fundacao Osvaldo Cruz
  • São Paulo, Brazil
    • Centro de Pesquisa Clínica do Instituto da Criança HC - FMUSP
• Colombia
  • Bogotá, Colombia
    • Fundación Cardioinfantil-Instituto de Cardiología

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 98 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with a diagnosis of Achondroplasia aged 3 years or older in Argentina, Brazil and Colombia

Description

Inclusion Criteria:

1. Individual with a documented diagnosis of achondroplasia based on:

   1. Genetic confirmation of achondroplasia and/or
   2. Clinical diagnosis of achondroplasia (clinical examination and/or radiological assessment)
2. ≥ three years of age at the time of enrollment
3. Has the cognitive and linguistic capacities necessary to complete questionnaires in the language of his/her country (and/or parents/legally acceptable representatives, as applicable)

4. Agrees to participate in the study and has read, understood, completed and signed:

   1. Informed Consent Form (ICF) - for adult subjects
   2. Informed Assent Form (IAF) - for minor subjects, accompanied by a parental ICF completed by their parents/legally acceptable representatives. The age at which the minor subjects sign the IAF will be subject to local requirements.
5. Has medical records available for the three years prior to the date of enrollment.

Exclusion Criteria:

1. Currently participating, or participated in the last six months, in

   1. a clinical trial of a medicinal product or medical device or
   2. other non-clinical or low interventional studies
2. Currently participating or has participated in any BioMarin study at any time.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort
Cohort 1; Includes age group 3-5 with a cap at 20 subjects. This is a retrospective, observational study
Cohort 2; Includes age group 6-10 with a cap at 30 subjects. This is a retrospective, observational study
Cohort 3; Includes age group 11-15 with a cap of 30 subjects. This is a retrospective, observational study
Cohort 4; Includes age group 16-20 with a cap of 20 subjects. This is a retrospective, observational study
Cohort 5; Includes age group 21-30 with a cap at 20 subjects. This is a retrospective, observational study
Cohort 6; Includes age group 31-40 with a cap at 20 subjects. This is a retrospective, observational study
Cohort 7; Includes age group 41 and over with a cap at 35 subjects. This is a retrospective, observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healthcare resource use	Healthcare resource use will be collected from medical records and through patient questionnaires. Data collection from medical records will be supplemented by records provided by the subject and, if necessary, confirmed by the family doctor. Healthcare resource use will be collected via validated and structured questionnaires	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Socio-economic burden	Data about socio-economic burden will be collected via validated and structured questionnaires specifically the Work and Productivity and Activity Impairment (WPAI-SHP)	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Pediatric Functional Independence Measure (WeeFIM)	The WeeFIM measures the need for assistance and the severity of disability in children between six months and seven years of age. The instrument consists of 18 items covering three domains: self-care, mobility, and cognition. The mean total score within each domain and the overall total score will be summarized. The study will be assessing subjects aged from 3 to 17 years	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Adolescent Pediatric Pain Tool (APPT)	The APPT is an instrument for self-reporting of pain by children and adolescents aged 8-17 years. Five subscale scores will be summarized on the analysis population	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Pediatric Quality of Life Inventory (PedsQL)	The PedsQL is comprised of four dimensions: Physical, Emotional, Social, and School Functioning. The overall score for each dimension is defined as the mean score for each item involved in the dimension. The overall score for each dimension and the mean total score across dimensions will be summarized for each report.	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Quality of Life Short Stature Youth (QoLiSSY) Questionnaire	The QoLISSY Questionnaire for children and adolescents consists of the core QOL dimensions: Physical, Social and Emotional, and three predictors of quality of life: Coping, Beliefs and Treatment. The QoLISSY total score is calculated by the sum of the means in the physical, social and emotional sub-scales divided by 3.	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Nottingham Health Profile(NHP) Questionnaire	The NHP is a generic quality of life survey used to measure subjective physical, emotional, and social aspects of health. The NHP total score is calculated by averaging the six domain scores.	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Brief Pain Inventory-Short Form (BPI-SF) Questionnaire	The BPI-SF is used to assess clinical pain. A mean severity score and mean interference score will be calculated and summarized for the analysis population	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Questionnaire	EQ-5D-5L questionnaire has 5 dimensions: "Mobility", "Human Autonomy," "Current Activities", "Pain / Discomfort", "Anxiety / Depression" and all dimensions are described by 5 problem levels corresponding to patient response choices. A quality of life score is obtained according to the answers to the questionnaires.	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Child Behaviour Checklist (CBCL)	The CBCL questionnaire is completed by the parent to assess the child behavioral and emotional problems. The questions are grouped into eight categories which focus on different aspects of behavior: aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, somatic complaints, social problems, thought problems and withdrawn/depressed.	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020
Understanding the Impact of Achondroplasia on Quality of Life Questionnaire	Impact on anxiety, depression, sleep disturbance and impact on relationships with others (spouse/partner family members, friends), social life and activities, perception of health, self-esteem, plans/ambitions for the future.	Once at start of study per subject through completion of questionnaires and via retrospective review of historical data. These will be assessed at end of study with the final Clinical Study Report, May 2020

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Height	Height measurements will be collected from retrospective data where available for standing and sitting height measurements. The height data will be measured in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment
Measurement of Weight	Weight will be collected from retrospective data collected and will be entered in kilograms.	Retrospective data will be collected for 3 years prior to date of enrolment
Body Mass Index (BMI)	Body Mass Index is calculated using height and weight. Body Mass Index (BMI) will be measured in kg/m2	Retrospective data will be collected for 3 years prior to date of enrolment
Head Circumference	Head Circumference will be collected from retrospective data collected and will be entered in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment
Upper and Lower Arm Length	Upper and Lower Arm Length will be collected from retrospective data collected and will be entered in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment
Iliac Height (hip to floor)	Iliac Height (hip to floor) will be collected from retrospective data collected and will be entered in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment
Subischial Length	Subischial Length will be collected from retrospective data collected and will be entered in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment
Thigh Length	Thigh Length will be collected from retrospective data collected and will be entered in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment
Knee Height	Knee Height will be collected from retrospective data collected and will be entered in centimetres.	Retrospective data will be collected for 3 years prior to date of enrolment

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2019
• Primary Completion (Actual): February 6, 2021
• Study Completion (Actual): February 6, 2021

Study Registration Dates

• First Submitted: January 16, 2019
• First Submitted That Met QC Criteria: March 11, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 5, 2021
• Last Update Submitted That Met QC Criteria: April 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Bone Diseases, Developmental; Osteochondrodysplasias; Achondroplasia
• Other Study ID Numbers: 111-502

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No