Starts:

Thursday, September 22nd
4:30pm-6:00pm EDT

Category:

Topical Workshop

Tracks:

Assessment, Diagnosis & Measurement of Pain

Room

715 B

Utilization of Pain Biomarkers as the Basis for Decisions in the Therapeutic Development Process and in Clinical Practice: New Approaches from INTEGRATE-Pain

The workshop will open with an introduction to the INTEGRATE-Pain consortium, which seeks to improve the understanding and treatment of pain through transatlantic R&D. It will also provide an overview of different categories of biomarkers and how each type can be integrated into the therapy development process and clinical practice. The session will then feature presentations from three biomarker researchers who will describe their progress and lessons learned when developing functional preclinical biomarkers for target engagement, clinical patient stratification biomarkers for chronic pelvic pain, and a clinical biomarker signature to facilitate treatment decisions in adolescents with high-impact musculoskeletal pain. The INTEGRATE-Pain consortium includes NIH staff who are affiliated with the National Institutes of Health (NIH ) Helping to End Addiction Long-term (HEAL) InitiativeSM , the NIH Pain Consortium and members of the Innovative Medicine Initiative (IMI) PainCare consortium, a public-private partnership for health between the European Union and European pharmaceutical companies. INTEGRATE-Pain promotes U.S./European cross-fertilization on pain biomarkers. Upon completion of this workshop, the audience will be informed on INTEGRATE-Pain’s efforts to advance the field of biomarkers, will gain an understanding of the biomarker development process and will know about several exciting biomarker signatures under development.

Presentations

Time
4:30pm EDT6:00pm EDT

Back Translation of Functional, Pharmacodynamic Pain Biomarkers into Rodents

Tracks: Assessment, Diagnosis & Measurement Of Pain
Categories: Topical Workshop
Presented By: Dr. Tony Blockeel

As part of the BioPain subtopic of IMI-PainCare, multiple pharmacodynamic (PD) biomarkers of nociceptive system function are being back translated from humans to rodents and their translatability assessed, specifically in relation to the effects elicited by the administration of three model compounds (lacosamide, pregabalin & tapentadol). Four primary assays are being utilized in this project: peripheral nerve excitability testing (threshold tracking), ii) somatosensory-evoked, spinal potentials (N13 response), (iii) EEG ± laser-evoked potentials (LEPs) and (iv) functional magnetic resonance imaging (fMRI). Here we will provide an overview of this effort, with a specific focus on comparisons between human and rodent LEPs. In brief, our work demonstrates that LEPs with features comparable to those recorded in humans can be reliably recorded in awake, freely-moving rats. Administration of the three model compounds significantly reduces their amplitude, with a temporal profile consistent with each drugs PK profile. The compounds also modulate concurrently recorded resting state spectral power and auditory evoked potential amplitude, providing additional insights into non-specific effects of the compounds on CNS function (e.g. sedation). With the aid of extensive PK and PD profiles generated for each compound (including within-subject PK & PD), we will present the PK-PD relationships describing these pharmacological effects.

4:30pm EDT6:00pm EDT

Deep Phenotyping to Improve our Understanding of Chronic Pelvic Pain

Tracks: Assessment, Diagnosis & Measurement Of Pain
Categories: Topical Workshop
Presented By: Prof. Katy F. Vincent

Chronic pelvic pain is common, affecting almost one quarter of women worldwide, with a significant impact on quality of life and high associated financial cost. The diagnosis of underlying pathology is difficult and frequently requires multiple surgical procedures often under different specialists. It is perhaps unsurprising therefore that the focus of biomarker research in this field has been non-invasive diagnostic tests. The TRiPP subproject of IMI-PainCare is taking a different approach, aiming to use biomarkers to identify underlying pain pathways rather than the presence of disease. This multi-site study integrates detailed phenotypic data with genomics and plasma proteomics and metabolomics in a cohort of almost 800 woman (556 with pelvic pain and 230 pain-free controls) and expands this data-set with additional questionnaires and psychophysical assessments in a subset. Additionally, our design allows us to specifically explore associations of endometriosis and of bladder symptoms. We will present results from integrative analyses of this rich dataset, determining key pathways underlying pain in women with pelvic pain and identifying clinically meaningful subgroups and associated biomarkers. Ultimately we hope this strategy will identify novel therapeutic targets, inform a more personalised approach to treatment and allow refinement of preclinical models to optimise drug discovery.

4:30pm EDT6:00pm EDT

Integration of Pain Biomarkers into the Therapeutic Development Process and into Clinical Practice

Tracks: Assessment, Diagnosis & Measurement Of Pain
Categories: Topical Workshop

Development of novel pain therapeutics continues to present significant challenges, demonstrated by data showing only a 2% probability of drug approval for Phase I candidate pain therapeutics compared to an overall 10% probability in other disease areas.  One reason for the low probability of clinical success is the lack of biomarkers that can facilitate dose selection and clinical trial design.  It has been shown that patient selection biomarkers can improve clinical success by as much as 17.5%.  This presentation provides an overview of the different uses for biomarkers and how each type of biomarker is utilized in the therapeutic development process.  Evidentiary criteria for biomarker validation will also be discussed, followed by a brief overview of how biomarker development has been integrated into the therapeutic development programs supported by the HEAL initiative. The NIH HEAL Initiative supports the development of biomarkers for pain with funding opportunities that encourage a rigorous, milestone-driven approach aligned with FDA standards. Further, HEAL offers separate opportunities to develop biomarkers in conjunction with therapeutic development and clinical testing as part of its Early Phase Pain Investigation Clinical Network (EPPIC-Net) and the HEAL Therapeutic Development Program.

4:30pm EDT6:00pm EDT

Signature for Pain Recovery IN Teens (SPRINT): Biomarker Signature Detection in a Multivariate Dataset Leveraging Supervised Machine Learning algorithms

Tracks: Assessment, Diagnosis & Measurement Of Pain
Categories: Topical Workshop
Presented By: Dr. Laura Simons

Up to 5% of adolescents suffer from debilitating, chronic musculoskeletal (MSK) pain affecting quality of life, school attendance, mood, and family function, and posing a significant economic burden. Only 40%-60% of adolescents with chronic MSK pain sustain significant improvements in clinical endpoints of pain severity and functional disability. Discovery of robust markers differentiating recovery versus persistence is essential to develop more resource efficient and patient-specific treatment strategies and to conceive novel approaches that benefit patients. Signature for Pain Recovery IN Teens (SPRINT), integrates four major domains: blood (immune markers), psychophysiologic (QST), imaging (brain structure and function), and patient report (demographic, physical, psychological) metrics. These selected metrics have robust associations with pain and function but have been limited by sample size, single metric assessment, and moderate effect sizes. This study represents the largest cohort of adolescents with chronic MSK pain deeply characterized to derive a prognostic biological signature of pain and functional recovery leveraging  a multivariate computational analysis pipeline which includes cross-validation, for the extraction of reliable results from this multilayered and complex dataset.

Presenters

Prof. Katy F. Vincent

Associate Professor, Senior Fellow in Pain in Women
University of Oxford

Dr. Tony Blockeel

Research Fellow
School of Physiology, Pharmacology & Neuroscience, University of Bristol, England

Dr. Mary Ann Pelleymounter

Program Director
NINDS/NIH

Dr. Laura Simons

Professor
Stanford University