NGS Strategy Effectiveness in Molecular Diagnosis

The coming out of Next Generation Sequencing (NGS) technologies, with documented advantages and reduced costs respect to Sanger sequencing, has provided new appealing approaches to diagnostic testing. Despite this, its use for routine diagnostic purposes requires certification in terms of reliability, as well as a cost-effectiveness evaluation.

To test the feasibility of using the Ion Torrent Personal Genome Machine (PGM) in clinical diagnosis, we assessed its performance to detect point mutations and big rearrangements previously identified with standard techniques. The diagnostic accuracy and the cost-effectiveness will be evaluated by Health Technology Assessment (HTA) analyses.

Study Overview

• Status: Completed
• Conditions: Osteogenesis Imperfecta; Multiple Osteochondroma
• Intervention / Treatment: Diagnostic test: NGS molecular screening

• Study Type: Observational
• Enrollment (Actual): 400

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 400 DNA samples coming from MO and OI patients (including either dominant and recessive forms) will be included in the study (250 affected by MO and 150 by OI).

Description

Inclusion Criteria:

• Clinical diagnosis of Multiple Osteochondroma
• Clinical diagnosis of Osteogenesis Imperfecta

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MO patients	Diagnostic test: NGS molecular screening
OI patients	Diagnostic test: NGS molecular screening

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the accuracy of the Ion Torrent PGM platform for genetic variant detection (Diagnostic sensitivity evaluation)	The accuracy of the Ion Torrent Personal Genome (PGM) to identify disease-causing mutations in patients affected by Multiple Osteochondromas (MO) and Osteogenesis Imperfecta (OI) needs to be validated for its routine diagnostic clinical use. To asses this, we will compare results obtained with the new NGS approach with those previously obtained with standard techniques (DHPLC/Sanger + MLPA) in a number of MO and OI patients.	at 30 months
HTA analysis to assess the cost-effectiveness, organizational and social implications of a screening strategy based on the IonPGM platform	To demonstrate the pertinence in the use of this innovative technology in health care, we will examine the medical, social and economic implications according with Health Technology Assessment (HTA), a multi-disciplinary field of policy analysis applied to many different health care technologies before their diffusion and use. HTA aims at evaluating the real effectiveness of medical interventions, their proper use, access criteria and qualitative improvements, the clinical and organizational benefits, therefore suggesting how to manage, promote and discourage them.	at 36 months

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli
• Collaborators: Catholic University of the Sacred Heart; Regione Emilia-Romagna

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 18, 2018
• Last Update Submitted That Met QC Criteria: June 14, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Neoplastic Syndromes, Hereditary; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Bone Diseases, Developmental; Osteochondrodysplasias; Collagen Diseases; Exostoses; Hyperostosis; Osteogenesis Imperfecta; Osteochondroma; Exostoses, Multiple Hereditary; Osteochondromatosis
• Other Study ID Numbers: PRUA1GR-2013-00000177

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan

Drug and device information, study documents

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