NEW EVIDENTIARY APPROACHES TO OLD CHALLENGES IN TMD/TMJ ARTHROPLASTY - PowerPoint PPT Presentation

Lisa Torosyan, CDRH/FDA MDEpiNet, Oct 20, 2017 NEW EVIDENTIARY APPROACHES TO OLD CHALLENGES IN TMD/TMJ ARTHROPLASTY 1

TMD/TMJ Arthroplasty Biomarkers: Narrowing the Gap between Currently Available and Urgently Needed Ø Poor predictability of treatment outcomes as a main challenge: Ø Inter-individual variability of TMD severity and clinical manifestations Ø Patient’s sex and other treatment outcome modifiers Ø The need for diagnostic and prognostic TMJ Arthroplasty biomarkers: Ø Intention-to-Treat (ITT) subpopulation for TMJ replacement Ø Predictive assessment of real-world device performance Ø Prevention and diagnostic/therapeutic management of adverse outcomes Ø The promise of new (in silico) evidentiary approaches for facilitating Precision/Stratified Medicine applications to TMD/TMJ Arthroplasty 2

TMJ – not just another joint: genes involved in TMJ Abnormal Morphology and Osteoarthritis are also associated with Neurological Functions TMJ Morphology & Inflammation Neurological Functions Image created using Ingenuity Pathway Analysis 3

TMD Heterogeneity: a major factor that complicates treatment choices Degenerative and ankylotic changes as indications for TMJ REPLACEMENT TMJ Osteoarthritis TMDs (eg, chronic pain – nociceptive, neuropathic, etc.) 4

Patient-Procedure-Device Impacts on TMJ Arthroplasty Outcomes: faulty device or individual susceptibility ? Patient Procedure ? Device ? 5

The Great Promise of ‘Omic Research for TMD/TMJ Arthroplasty applications q GWAS hold great promise for advancing our understanding of the genetic contributions …, risk factors for susceptibility and prognosis, and the development of individualized dental [and craniofacial] medicine. q …however, we are still in the early stages of the translation of genomics to clinic [and regulatory] practice (Kim et al 2012). 6

Demographic Challenges in TMD Biomarker Discovery, or why pharmacogenetics needs pharmacoepidemiology High C • “A SNP in PTGS1 (rs3842803) showed the strongest association with global psychological symptoms. However, … the SNP remained strongly associated only in African-Americans.” 7

Biomarker-based Evidentiary Approaches to TMD/TMJ Arthroplasty ü Biological and clinical plausibility of study endpoints and biomarkers : ü Better understanding of molecular/mechanistic underpinnings ü Improved pre-selection of biomarker candidates for qualification and validation steps ü Clinical and regulatory relevance of putative TMD/TMJ Arthroplasty biomarkers: ü New druggable targets for different TMDs ü Well-defined target subpopulations ( eg , ITT for TMJ Replacement) ü Proactive surveillance of adverse events in TMJ Arthroplasty ü Less burdensome and more effective preclinical testing of TMJ devices ü Cost/time-efficient solutions for TMD-related Precision Medicine applications (eg, biomarkers for individuals and sex/race-stratified subpopulations) ü The guiding role of EPIDEMIOLOGIC EVIDENCE for effective discovery of biomarkers applicable to various subpopulations with TMD/TMJ Arthroplasty 8

Pharmacoepidemiologic Promise of Registry-based Networks for TMD/TMJ Arthroplasty 9