There is a very high need for improving health care for the management of pain, which is the scope of this Topic. As acute and persistent pain of different origin represent common medical, social, and economic burden, and its pharmacotherapy is still an unresolved issue. In order to achieve an optimised management of pain patients and to support the process of decision making in clinical practise, objective assessments of the treatment success are needed. Successful novel approaches for patient stratification could reduce the still high number of non-responders. Developing new analgesics is challenging because promising preclinical data are often not reproduced in the clinic, and often without knowing the reason. Improved pharmaco-dynamic biomarkers could define whether an intended target is adequately engaged, greatly reducing the risk in clinical development of a new drug. Finally, for many pain indications, there are no adequate preclinical models available, precluding preclinical investigations and leaving affected patients with little hope of relief. The goal of this Topic is to make advances in three pain areas in a complementary manner. These three Subtopics, each of which addresses a specific scientific challenge, together offer significant opportunities for cross-fertilisation:
Subtopic 3A: using Patient Reported Outcome Measures to improve the management of acute and chronic pain (PROMs);
Subtopic 3B: improving the translatability of pharmacodynamic biomarkers in pain pathways of healthy subjects and preclinical species (BIOM);
Subtopic 3C: improving translation in chronic pelvic pain (CPP).
Stage 1 short proposals from Applicants should address only one of these Subtopics. Applicants can submit a proposal to any of the subtopics and are not obliged to apply for all.
Whilst contributions to each subtopic will require mobilization of specialist expertise, it is a key objective of this Topic to create a research platform for pain that will contribute significantly to reduce fragmentation and generate highest impact on the whole area. Thus, to maximise cross-learnings and full data sharing while insuring economy of scale, it is envisaged that a single full proposal is submitted at stage 2. This full proposal will include activities covering all three subtopics, as well as overarching joint activities such us overall governance, communication and dissemination, and data and knowledge management.
Thus at Stage 2, the full proposal will be submitted by the consortium created by the merger of the winning Applicant Consortia of all subtopics (3A+3B+3C) with the Industry consortium.
Stage 1 short proposals from Applicants should address only one of the Subtopics. Applicants can submit a proposal to any of the subtopics and are not obliged to apply for all.
Whilst contributions to each subtopic will require mobilization of specialist expertise, it is a key objective of this Topic to create a research platform for pain that will contribute significantly to reduce fragmentation and generate highest impact on the whole area. Thus, to maximise cross-learnings and full data sharing while insuring economy of scale, it is envisaged that a single full proposal is submitted at stage 2. This full proposal will include activities covering all three subtopics, as well as overarching joint activities such as overall governance, communication and dissemination, and data and knowledge management.
Subtopic 3A PROMs:
The scope of the PROMs Subtopic will be to establish operational benchmarks in the management of post-operative and other acute pain conditions, and in the prevention of its chronification, as well as in the management of chronic pain conditions such as neuropathic pain and chronic pelvic pain (CPP). In particular, these will allow identification of risk factors for the transition of acute into chronic neuropathic post-surgical pain, and thus enable novel therapeutic mitigations to be developed. The results are expected to provide motivation for all stakeholders involved in pain management (e.g. HCPs, patients, scientific societies, and policy makers) that the use of PROMs to monitor post-operative and other pain conditions in daily clinical practice, together with their documentation into a readily accessible database, is of benefit for assuring the success of treatments and aimed at preventing pain chronification.
Subtopic 3B BIOM:
The scope of the BIOM Subtopic is to generate valid clinical pharmacodynamic biomarkers of peripheral, spinal and central neuronal activities, and to develop detailed PK/PD models for drugs which target these compartments in healthy subjects. The PD read-outs should include threshold tracking, quantitative pharmaco-EEG, laser-evoked event-related potentials (ERPs), pharmaco- or evoked-pain fMRI, and will be compared to pain ratings assessed by visual analogue scales.
The clinical biomarkers will be back-translated into rodents to investigate the effect of comparable pharmacological exposures. As with the clinical studies, preclinical PK/PD models will be generated, and the results compared to more classical pain model outcomes to gain understanding of potential PD efficacy relationships
Subtopic 3C CPP:
Despite the high incidence of chronic pelvic pain, understanding of the pathological conditions leading to it is sparse, and diagnostic tools such as biomarkers are unspecific or do not exist at all. Consequently the scope of the subtopic CPP is to improve this unsatisfactory situation by thorough analysis of patient phenotypes. This should identify specific clinical and molecular markers which would permit a patient stratification which increases the chances for selecting effective therapies. Back-translation of clinical biomarkers into preclinical models is sought, as well as the subsequent refinement of these models to more adequately reflect clinical disease phenotypes. Such refined models will generate new opportunities to evaluate the clinical potential of novel therapeutics.
The overall key impact of the execution of this topic, via its three components as indicated in the subtopics, will be to improve and standardise different patient-centric treatments for the management of acute and chronic pain, ostensibly the most burdensome disease in terms of patient suffering and healthcare costs. In particular, it is anticipated that new tools and methods will pave the way to the identification of improved treatments which are able to reduce both the disease intensity of acute and chronic pain and the risk of chronification of post-surgical and other acute pain conditions, thus assuring a better quality of life for pain patients. Another impact will be that by deepening the disease understanding, stratification and enrichment markers will be identified and refined, helping to enable precision medicine.
In addition, it is expected that better understanding of the successful translation from preclinical into clinical studies, and of back-translation from the clinic into improved preclinical models, will reduce attrition rates in drug discovery, and enhance the feasibility and speed of the development of novel drugs.