Background and Aim: Harmonizing outcome assessment in clinical trials is a challenge but would much enhance comparative effectiveness research and future allocation of patients to suiting treatments. A core outcome set (COS) should help to harmonize outcome assessment and should therefor consist of most critical, patient relevant outcome domains to be assessed in each single clinical trial. A COS comprises of defined outcome domains (WHAT to measure) and referring measurement instruments (HOW to measure). VAPAIN works on a Core Outcome Set (COS) for Interdisciplinary Multimodal Pain Therapy (IMPT)a,b.
Method: A multifaceted procedure was applied, comprising systematic reviewsc and consensus processes (see fig 1 and 2). In a first step, outcome domains had been proposed by an international panel regarding IMPT effectiveness and providing definitions alongsidea,b. This step followed common guidelinesd (COMET handbook, fig. 1).
In a subsequent step it was supposed to identify relevant measurement instruments and to investigate their psychometric soundness. COSMIN guidelines had been appliede
Ethics and Dissemination: The methods and procedure of the study are developed in compliance with the ethical principles of the Helsinki Declaration and Good Epidemiologic Practice.
Results: No matching instruments have been identified for all VAPAIN domains for several reasons (except patient perception of treatment goal achievement and health related quality of life- still under investigation):
1. Definition of the VAPAIN domain was not suitable for further operationalization for the domains pain intensity, pain frequency, emotional wellbeing
2. Identified instruments did not provide any definition for the domains productivity, physical activity, satisfaction with social roles and activities
3. Identified instrument provided definition but not matching the consented VAPAIN definition regarding the domains productivity, physical activity, satisfaction with social roles and activities
4. There had been no single patient reported outcome according to the definition of Cochrane for the domains productivity, physical activity, satisfaction with social roles and activities
5. Content validity has not been investigated in any of the identified instruments for productivity, physical activity, satisfaction with social roles and activities
Implications: VAPAIN has been successful in recommending 8 core outcome domains for assessing the effectiveness of interdisciplinary pain management approaches.
For identifying relevant measurement instruments there have been considerable barriers. An unexpected main barrier was the insufficiency of definitions of common constructs in pain management (such as emotional well being) which hampered completely either estimation of content validity or, in case of instrument development, operationalization of construct into items. A surprising amount of measurement instruments lacked any definition at all. Validity, especially content validity, is therefore not to be estimated.
At this stage no measurement instrument could be recommended when referring to common methodological standards.

* VAPAIN (Validation and Application of a patient relevant core outcome set to assess effectiveness of multimodal PAIN therapy) is funded by the German Ministry of Education and Research (01GY1326).  Contact: vapain@uniklinikum-dresden.de

a Kaiser U, Kopkow C, Deckert S, Sabatowski R, Schmitt J. Validation and application of a core set of patient-relevant outcome domains to assess the effectiveness of multimodal pain therapy (VAPAIN): a study protocol. BMJ open. 2015;5(11):e008146.
b Kaiser U, Kopkow C, Deckert S, Neustadt K, Jacobi L, Cameron P, et al. Developing a core outcome domain set to assessing effectiveness of interdisciplinary multimodal pain therapy: the VAPAIN consensus statement on core outcome domains. Pain. 2018;159(4):673-83
c Deckert S, Kaiser U, Kopkow C, Trautmann F, Sabatowski R, Schmitt J. A systematic review of the outcomes reported in multimodal pain therapy for chronic pain. Eur J Pain. 2016;20(1):51-63.
d Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. Trials. 2017;18(Suppl 3):280
e https://www.cosmin.nl/

FROM WHAT TO MEASURE TO HOW TO MEASURE - EXPERIENCES FROM THE VAPAIN INITIATIVE