Clinical trial NCT02244450: Generalized Neonatal Screening of Severe Combined Immunodeficiencies
Official title: Evaluation of the Clinical Utility and Cost Effectiveness Ratio of Generalized Neonatal Screening for Severe Combined Immunodeficiencies (SCID) by Quantification of TRECs on Guthrie Cards
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Combined Immunodeficiency, Atypical
Keywords: Neonatal screening
severe combined immunodeficiency
T-cell Receptor Excision Circle
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2014-09-19
Enrollment: 190539
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Severe combined Immunodeficiencies ( SCID ) are a group of inherited diseases of the immune system by characterised profound abnormalities of T cell development . Infants with SCID require prompt clinical response to Prevent life -threatening infection and studies show significantly improved survival in babies Diagnosed at birth as a result of previous family history . SCID follows criteria for population -based newborn screening since it is asymptomatic at birth and fatal within the first year of life, the confirmation of the disease is easy, there is a curative treatment , and it is known that early stem cell transplantation improves survival . Quantification of TRECs (T- cell receptor excision circles ) in DNA extracted from Guthrie samples is a sensitive screening test for Specific and SCID .

The investigators propose in this study to perform a neonatal screening of SCID , in a population of 200,000 babies over a period of two years .

The investigators propose to study the clinical utility and cost effectiveness ratio, and SCID screening to demonstrate that could result in a broad benefit to Individuals detected , making screening relatively cost-effective in spite of the low incidence of the disease .

Detailed description: The project proposes to study the feasibility and cost-effectiveness ratio ( time management and life expectancy to 10 years) of generalized neonatal screening for SCID children by offering this screening to 200 000 children (100 000 children per year) over the entire territory. Prospective control group consists of children diagnosed with SCID out of 700,000 annual births who do not benefit from screening.

The protocol will be leant against the existing newborn screening , that is to say two more drops of blood are placed on a second Guthrie card when current screening (72 hours of life ) is performed after parents' information and consent. Eleven newborn screening regional associations will be involved with the inclusion of children in about 50 maternity hospitals. The card drawn for the protocol will follow the usual network except that the test for quantifying TRECs will be realized in two laboratories instead of eleven laboratories assigned to RA . Investigative Regional Associations (RAs) represent nearly 600,000 births / year and the amount of 200,000 children will be achieved in two years (duration of inclusion) . All children born in the participating maternity may be included if they meet the inclusion criteria. The result of the screening test for SCID will be available within 21 days after birth, provided that there is no need to request a new sample.

At each of eleven RA is associated a pediatrician referent for immune deficiencies, member of the french reference center (CEREDIH) and who will be responsible to call the parents, offer them a consultation and further exploration if the result of screening is assumed positive.

Analysis of cards from 200,000 children will give the following information:

* Number of children with a presumptive positive screening , requiring a call by the referent pediatrician, consultation and exploration of lymphocyte subpopulations
* Number of children with a negative screening
* Number of children with an inconclusive screening (lack of TRECs and lack of amplification of the reference gene) and requiring a new card,

A micro- costing study will be conducted to assess the cost of testing .

This group of 200,000 children is the experimental group to assess the cost of screening , acceptability by parents (participation rate), the recall rate for abnormal or inconclusive result, the rate of follow-up time for results , the incidence of disease . It will also allow to calculate the specificity of the method .

At the end of the inclusions, the vital status at 18 months with cause of death will be sought for the 200 000 children included , with the CESP ( Centre de Recherche en Epidemiologie et Santé des Populations) via RNIPP (Répertoire National d'Identification des Personnes Physiques) and CepiDc ( Centre d'Epidémiologie sur les causes médicales de décès) . This will establish whether there are SCID in this population which were not detected at birth. Furthermore, the investigators include in the study SCID children diagnosed without screening by pediatricians local referents DIP (including Necker main transplant center) . This will enable to approach the sensitivity of the method . All these data allow the calculation of the predictive values of the test.

In this experimental group will be isolated a group of individuals who screened positive and diagnosed as true SCID . Clinical data for these patients will be collected in an electronic CRF ( CRF ) by the pediatrician referral protocol (Dr Thomas C ) , including:

* The dates and results of explorations : lymphocyte subpopulations , blood count, determination of immunoglobulin levels
* The diagnosis made with identification of the genetic defect
* The date of care before curative treatment ( protected area isolation , anti -infective drugs )
* , Bacterial , fungal anti -viral treatments , and other
* The date of transplant, type of transplant or other treatment ... ...

Eligibility criteria: Inclusion Criteria:

* Screening Group: Newborn on day 3 of birth (premature and non premature)
* Control group: Patients diagnosed with SCID without screening at participating centers

Exclusion Criteria:

* Lack of parental consent
* Children whose parents are adults under guardianship,
* Children without health insurance, for the screening group:
* The early exit of the child from the maternity hospital

Primary outcomes:
measure: cost / efficiency ratio of the implementation of the generalized neonatal screening of SCID at birth
timeFrame: 18 months
Secondary outcomes:
measure: Cost / efficiency ratio of the implementation of the generalized neonatal screening of SCID at birth
timeFrame: 10 years
measure: The cost of care during the first 18 months of life per child enjoying an early curative treatment in the first 4 months of life.
timeFrame: 18 months
measure: Length of hospitalization of children with SCID in the first 18 months of life
timeFrame: 18 months
measure: number of avoided deaths
timeFrame: 18 months
measure: number of detected SCID patients
timeFrame: 18 months
measure: number of patients detected with other T lymphopenia (SCID variants , DiGeorge , severe T lymphopenia non SCID ... )
timeFrame: 18 months
measure: number of false negative and false positive results
timeFrame: 18 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers Private Hospital Clinique de l'Anjou
city: Angers
country: France
facility: Angers University Hospital
city: Argenteuil
country: France
facility: Argenteuil Hospital
city: Aulnay-sous-Bois
country: France
facility: Aulnay-sous-Bois Hospital CHI Robert Ballanger
city: Bordeaux
country: France
facility: Bordeaux Maison de Santé Protestante Bordeaux Bagatelle
city: Bordeaux
country: France
facility: Bordeaux Private Hospital Polyclinique Bordeuax Nord Aquitaine
city: Bordeaux
country: France
facility: Bordeaux University Hospital
city: Corbeil Essonnes
country: France
facility: Corbeil Essonnes Hospital Sud Francilien
city: Créteil
country: France
facility: Créteil Hospital
city: Dijon
country: France
facility: Dijon University Hospital
city: Grenoble
country: France
facility: Grenoble University Hospital
city: Le Blanc Mesnil
country: France
facility: Le Blanc Mesnil Private Hospital
city: Lens
country: France
facility: Lens Hospital
city: Libourne
country: France
facility: Libourne Maternity Hospital
city: Lille
country: France
facility: Lille University Hospital
city: Lormont
country: France
facility: Lormont Maternity Hospital Rive Droite
city: Lyon
country: France
facility: Lyon Maternity Hospital
city: Lyon
country: France
facility: Lyon University Hospital
city: Marseille
country: France
facility: Marseille Saint-Joseph Hospital
city: Marseille
country: France
facility: Marseille University Hospital La Conception
city: Marseille
country: France
facility: Marseille University Hospital Nord
city: Marseille
country: France
facility: Marseille University Hospital
city: Meaux
country: France
facility: Meaux Hospital
city: Montreuil
country: France
facility: Montreuil Hospital CHI André Grégroie
city: Nantes
country: France
facility: Nantes University Hospital
city: Nantes
country: France
facility: Nantes Private Hospital Clinique Jules Verne
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: Paris Hospital Saint-Joseph
city: Paris
country: France
facility: Paris Necker University Hospital
city: Paris
country: France
facility: Paris University Hospital Armand-Trousseau
city: Paris
country: France
facility: Paris University Hospital Bichat
city: Paris
country: France
facility: Paris University Hospital Bicêtre
city: Paris
country: France
facility: Paris University Hospital Béclère
city: Paris
country: France
facility: Paris University Hospital Jean Verdier
city: Paris
country: France
facility: Paris University Hospital La Pitié Salpétrière
city: Paris
country: France
facility: Paris University Hospital Louis Mourier
city: Paris
country: France
facility: Paris University Hospital Necker
city: Poissy
country: France
facility: Poissy Hospital CHI Poissy-Saint-Germain
city: Pontoise
country: France
facility: Pontoise Hospital René Dubos
city: Rennes
country: France
facility: Rennes Private Hospital Clinique Mutualiste La Sagesse
city: Rennes
country: France
facility: Rennes University Hospital
city: Rennes
country: France
facility: Saint-Grégoire Private Hospital
city: Roubaix
country: France
facility: Roubaix Hospital
city: Saint-Herblain
country: France
facility: Saint-Herblain Private Hospital Polyclinique de l'Atlantique
city: Saint-Mande
country: France
facility: Saint-Mande Army Hospital Begin
city: Saint-Martin d'Hères
country: France
facility: Saint-Martin-d'Hère Private Hospital Clinique Belledonne
city: Strasbourg
country: France
facility: Strasbourg Private Hospital Clinique Adassa
city: Strasbourg
country: France
facility: Strasbourg University Hospital
city: Toulouse
country: France
facility: Toulouse Private Hospital Clinique Sarrus Teinturiers
city: Toulouse
country: France
facility: Toulouse University Hospital P. DE VIGUIER
city: Toulouse
country: France
facility: Toulouse University Hospital
Study officials:
affiliation: Nantes University Hospital
name: Caroline THOMAS, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Marie AUDRAIN, MD
role: STUDY_DIRECTOR
affiliation: Nantes University Hospital
name: Sophie MIRALLIE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thomas C, Durand-Zaleski I, Frenkiel J, Mirallie S, Leger A, Cheillan D, Picard C, Mahlaoui N, Riche VP, Roussey M, Sebille V, Rabetrano H, Dert C, Fischer A, Audrain M. Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results. Clin Immunol. 2019 May;202:33-39. doi: 10.1016/j.clim.2019.03.012. Epub 2019 Apr 1.
citation: Audrain MAP, Leger AJC, Hemont CAF, Mirallie SM, Cheillan D, Rimbert MGM, Le Thuaut AM, Sebille-Rivain VA, Prat A, Pinel EMQ, Divry E, Dert CGL, Fournier MAG, Thomas CJC. Newborn Screening for Severe Combined Immunodeficiency: Analytic and Clinical Performance of the T Cell Receptor Excision Circle Assay in France (DEPISTREC Study). J Clin Immunol. 2018 Oct;38(7):778-786. doi: 10.1007/s10875-018-0550-7. Epub 2018 Sep 24.