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Research Paper

Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting

Pogatzki-Zahn, Esther M.a,*; Liedgens, Hiltrudb; Hummelshoj, Lonec; Meissner, Winfriedd; Weinmann, Claudiad; Treede, Rolf-Detlefe; Vincent, Katyf; Zahn, Peterg; Kaiser, Ulrikeh; the IMI-PainCare PROMPT consensus panel

Author Information
doi: 10.1097/j.pain.0000000000002254

1. Introduction

More than 300 million surgeries are performed worldwide each year, and pain is one postoperative symptom that is still not managed well.17,18 The impact of postoperative pain is not only important for ethical reasons; pain can lead to impaired physical recovery,26 contributes to postoperative complications in general,46 might result in chronification of pain,16,20 and contributes to opioid dependency.5,32 Thus, adequate management of pain after surgery is one major goal during the perioperative period.

One main reason for suboptimal management of postoperative pain is a flaw in designing randomized controlled trials in this field. Common study endpoints unlikely to reliably show relevant treatment effects, and a heterogeneity of outcome assessment considerably hampers comparative effectiveness research related to perioperative pain management.19,44 More homogeneous and relevant outcome assessment, unbiased outcome reporting, and reporting of safety are important in postoperative trials and should follow certain standards.19,38

In general, outcome assessment in clinical trials is crucial to identify whether an intervention is effective and safe.49 Thus, it is important to choose relevant outcome parameters for the health condition, the intervention assessed, and for all stakeholders to be involved (including patients).50,51 As suggested, a core set of outcome measures is assumed to improve effectiveness research.49,50 Core outcome sets (COSs) consist of a minimum of outcome domains (concepts to be measured, a further specification of an aspect of health37) and corresponding measurement instruments to be assessed (outcome measures50). Developing COSs comprising of both outcome domains and thereafter measurement instruments is a multifaceted process, consisting of systematic research and consensus processes. Standards have been set and advanced during the past years by Core Outcome Measures in Effectiveness Trials [COMET];50). The first step comprises identification of outcome domains characterized by a structured procedure (eg, guided by the COMET handbook), transparency (eg, guided by the COS Star guidelines of reporting COS studies), and inclusion of relevant stakeholders and patient representatives.1 Within a setting comprising different modalities of treatment (here, surgical procedures and pain management), clarifying the scope of a COS is an essential prerequisite for reliable outcome assessment. As described in detail earlier,25 no such COS for perioperative pain management has been established so far.

The aim of this study was to develop a COS of domains referring to perioperative pain management after breast surgery (BS), sternotomy (ST), total knee arthroplasty (TKA), and endometriosis surgery (ES) in clinical trials, observational studies, and clinical practice by involving all relevant stakeholders, including patients. Because treatment aims and outcome assessment might be different across different surgical procedures, we chose 4 clinically relevant but different procedures (regarding type of tissue injury, body parts, and patient characteristics). The Delphi process is part of the EU-funded Innovative Medicines Initiative PainCare subproject Providing Standardized Consented PROMs for Improving Pain Treatment (PROMPT) (www.imi-paincare.eu), dedicated to achieve—at the end—a consensus on a COS of PROMs for assessing effectiveness of perioperative pain management of acute pain after surgery.

2. Methods

2.1. General considerations

The rationale and design for the consensus process within the PROMPT project are guided by the COMET recommendations 50 (Fig. 1), referring to postoperative pain in adult patients undergoing BS, TKA, ST, and ES and receiving perioperative pain management (scope), consisting of 2 arms—one for identifying core outcome domains and another for core outcome measurement instruments. Both arms start with systematic research and lead to different forms of consensus processes. Reporting of the processes will be based on the COS Star guidelines.29 The protocol for the complete process has been published elsewhere a priori.25 Four different surgical procedures were considered as relevant for identifying core outcome domains of perioperative pain management because outcome domains and measurement instruments might differ depending on the procedure, type of intervention, and patient population (also compare www.postoppain.org). The 4 surgeries, in particular, were chosen for several reasons such as (1) the differences in type and extent of tissue injury (soft tissue, bone/joint/visceral; inpatient vs outpatient), (2) the differences in patient populations (eg, young vs old patients; cancer vs noncancer patients, preoperative pain, or none), (3) the frequency of performance worldwide, (4) the reasonable and in part problematic occurrence of severe acute postoperative pain in a number of patients, (5) the potential of chronification, and (6) the differences in treatment options. Thus, the chosen procedures represent relevant issues of postoperative pain, including different treatment approaches (eg, regional vs systemic analgesics), several different surgical injuries (bone, visceral, and others), divergent patient populations (age, sex, and chronic pain patients such as those with endometrioses), and different surgical situations (eg, inpatient and outpatient surgery; Table supplement digital content 1, available at http://links.lww.com/PAIN/B320). Finally, as discussed earlier,25 by selecting a broad spectrum of surgeries and different requirements of perioperative pain management relevant for these procedures, we wanted to stress the question of developing either separate COS for perioperative pain management after each surgical procedure or an overarching COS comprising all.

Figure 1.
Figure 1.:
Agenda of IMI PROMPT consensus on core outcome domain and measurement set for perioperative pain management after the 4 indicated surgeries. The first part is related to domains and will lead to voting for a final core outcome domain set (COS domains, present article). The second part is related to measurement instruments related to the consented domains and will lead to voting for a final core outcome measurement set (COS measurements, next step). BS, breast surgery; ES, endometriosis surgery; PROMPT, Providing Standardized Consented PROMs for Improving Pain Treatment, subproject of the IMI Pain Care; ST, sternotomy; TKA, total knee arthroplasty.

To ensure comprehensiveness of a future COS for specific health conditions, theoretical frameworks should guide decision-making about the importance of core outcome domains. The framework recommended by OMERACT matches the purpose and need of PROMPT and was originally applied for arranging and structuring relevant outcome domains into relevant core areas.37 The focus on therapy aims as a prerequisite for deriving relevant outcome domains was chosen to facilitate discussion and enable greater focus of participants. Therapy aims have been understood as general objectives of acute pain management related to surgery (including BS, TKA, StS, and ES) to restore function (eg, physical and/or psychological) and reduce suffering from postoperative pain considering a patient-centered approach as well as the risks and benefits associated with the intervention within the first weeks after surgery. Thus, treatment aims and outcome domains should be considered closely related. Only aspects of health changed by a specific intervention should be reasonably taken into account as outcomes because this change is intended and supposed to be investigated by effectiveness studies. A domain was defined as a concept to be measured, a further specification of an aspect of health37 categorized within a core area.

2.2. Participants

For perioperative pain management, a considerable variety of stakeholders needs to be considered, especially regarding the latest acceleration in treatment development and multiprofessionality in this field.

To be eligible for the PROMPT consensus panel, participants had to be experts experienced in perioperative pain management (clinicians and researchers) after the 4 types of surgeries or having experienced such procedure themselves (patient representatives). For endometriosis, inclusion was extended to individuals experienced in unspecified treatment of endometriosis. Furthermore, pharma representatives, representatives of health technology assessment agencies, and regulators (experienced in drug development) were identified as important stakeholders in the field of perioperative pain management and thus were included. Because PROMPT is embedded into a larger project, and other processes will be based on future results from PROMPT, the panel was extended to include corresponding working group members of the IMI-PainCare project, of whom all are experts in the field of pain/pain research. All participants were recruited by official, established, and acknowledged scientific organizations in Europe. Stakeholder groups are provided in Table 1 along with involved scientific and patient self-help organizations as well as countries of heritage information on the stakeholder level (age, gender, experiences in consensus processes, and other factors) are provided as supplemental material (see table, supplement digital content 2-6, available at http://links.lww.com/PAIN/B320).

Table 1 - IMI PROMPT panel participants disposition.
Nominated by Invited Participation Years of experience [MD (range)] Years with experience in pain management and/or research Expertise Previous experience in consensus processes
No Yes
Anesthesiologists
Pain Specialists
IMI group (clinical)
Surgeons
Clinical psychologists
Physiotherapists
HTA/PRO experts and regulatory experts
Pain nurses
IMI-EFFPIA (pharmacists)
ESA, ESRA
EFIC
IMI
EFIC, IMI
EFIC, IMI
EFIC, IMI
IMI

EFIC, IMI
IMI
4
4
4
4
4
4
4

4
4
0
0
1
0
0
0
0

0
1
4
4
3
4
4
4
4

4
3
20 (6-42) 16.5 (6-40) 56.7% with expertise in clinic and research 55.3% experience with consensus processes
Nominated by Invited Participation Years of chronic pain (MD [range]) Years engaged as a patient representative (MD [range])
No Yes
Patient representatives EFIC, IMI 4 0 4 17.5 (0-34) 12 (5-23)
Invited Participation Age Gender
No Yes
Final number of participants 40 2 38 36.8% aged between 40 and 49 50% female
Delegee participated: Country
Austria Australia Belgium Germany Denmark Finland France Greece Island Norway The Netherlands Poland United Kingdom Sum
No 0 0 0 2 0 0 0 0 0 0 0 0 0 2
Yes 2 1 2 11 2 1 4 2 1 2 6 1 3 38
Overall participants/country invited 2 1 2 13 2 1 4 2 1 2 6 1 3 40
ESA, European Society of Anaesthesiologists; EFIC, European Pain Federation; ESRA, European Society of Regional Anesthesia and Pain Therapy; IMI-Group, IMI-PainCare Consortium.

For the consensus meeting, the following 3 different groups were created:

  • (1) The stakeholder group consisting of representatives of a specific stakeholder—eg, patients and clinical psychologists, etc.—ensures engagement in discussions as stakeholder representatives, not as individuals.
  • (2) The surgery group consisting of representatives of each stakeholder group—eg, BS with one of each stakeholder groups—ensures comprehensiveness in perspectives;
  • (3) The plenary group consisting of all panel members ensures transparency and legitimacy of processes and results.

2.3. Information sources and initial list of outcomes

According to the COMET data source (http://www.comet-initiative.org/) and to the best of our knowledge, no COS initiative is so far engaged in perioperative pain management in general or for the chosen procedures TKA, BS, and ST. In the field of endometriosis, several initiatives with different scopes addressed aspects or complete COS, either published as a report or a study protocol15,24,47,48 or not published yet but provided to IMI PainCare representatives [personal communication with Prof. Katy Vincent, Nuffield, United Kingdom: Email correspondence between 6th and 10th June 2018]. Yet to note, none is particularly dedicated to pain after surgery regarding endometrioses.

The consensus process on COS domains was prepared by 2 different arms (step 1, Fig. 1), regarding the different situations in COS development so far:

  • (1) An initial list of outcome domains considered in clinical trials, considering effectiveness/efficacy of perioperative pain management after TKA, BS, and ST, were created from 3 systematic reviews (registered in the PROSPERO database [CRD42018093838, CRD42018095142, and CRD42018095137] and final manuscripts of the SLRs are in preparation). Only explicitly indicated outcome domains by authors were considered to avoid interpretation bias by the IMI PROMPT steering committee.
  • (2) For endometriosis, previous results15,24,34,47,48 of other initiatives were provided to the panel. A scope into the literature revealed only few studies regarding our scope and not supporting a SLR in this field.

The complete initial list of outcomes for all surgery groups is provided in Table 2, grouped according to the OMERACT Filter 2.0 framework into 4 core areas (death, life impact, resource use/economic impact, and pathophysiological manifestations) and the area of adverse events (AE)37 as advised in preparation of the subsequent COS developmental process.1,3

Table 2 - List of initial outcomes derived from preparing systematic literature reviews, provided during the consensus finding (step 5).
Core areas as advised by OMERACT filter 2.0 Outcome domain Outcome subdomain Level 1 Outcome subdomain Level 2 (operationalization) TKA BS ST ES Definition and reference
Death x Reporting of number of deaths occurred within a clinical trial10
Life impact
Pain/Pain (incl level/degree/scale/score/incidence) x x x x* Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described for such damage (IASP terminology 2017).
*IMMPACT Recommendation13,45: 11-point (0-10) NRS of pain intensity, use of rescue analgesics, categorical rating of pain intensity in circumstances in which numerical ratings may be problematic
At rest x x x
During activity x x x
During coughing x
During deep breath x
Minimum x
Maximum x
Average x
Quality/Hyperalgesia (by self-report) x x x
Pain relief x x
Pain control x x
Percentile pain reduction x
Occurrence of unacceptable pain x
Localisation x
Tension x
Dysmenorrhea, dyspareunia, (nonmenstrual) pelvic pain, dyschezia, and abdominal pain x
Postoperative pain x
Overall pain x
Back pain x
Aggregate pain x
Lateral menstrual pain x
Painless first stage of labor x
Rectal pain x
Shoulder pain x
Thigh pain x
Voiding pain x
[Pain severity] [Not further specified]
At rest x
During activity x
Pain intensity x x x x [How much a patient hurts, reflecting] the overall magnitude of the pain experience [regarding the sensory aspect of pain] (adapted from10,45)
At rest x x x
At rest [Crosses in TKA,BS, ST] During Activity [Crosses in TKA, BS, ST] x x x
During coughing x
During deep breath x
Minimum x
Maximum x
Average x
Difference in time x
Pain Interference x x Consequences of pain on relevant aspects of a patient's life and may include the impact of pain on social, cognitive, emotional, physical, and recreational activities10
Quality of life x x x x* Health-related quality of life is the functional effect of a medical condition and/or is consequent therapy on a patient. It is thus subjective and multidimensional, encompassing physical and occupational function, psychological state, social interaction, and somatic sensation8,43
Physical function x x x x* Ability to carry out activities that require physical actions, ranging from self-care (activities of daily living) to more complex activities that require a combination of skills, often within a social context7
*IMMPACT Recommendation13,45: either measure; multidimensional Pain Inventory Interference Scale; Brief Pain Inventory interference items
Time to ambulation x
Mobilization x
Muscle strength/motor power x
Tension x x
Psychological function x x Impact on patient’s levels of anxiety, depression, anger, or other types of psychological distress. Anxiety refers to fear, extreme worrying and hyperarousal symptoms. Depression refers to negative mood, loss of self-confidence, loss of motivation and enjoyment. Anger refers to irritability and frustration.10
Fatigue x
Relaxation x
Emotional distress x [not further specified]
Anxiety x
Agitation x
Cognitive function x x Patient's levels of attention, memory, concentration, and perception. Attention refers to the ability to focus on tasks, and memory refers to the ability to recall information, concentration to the ability to sustain attention, and perception to the ability to interpret information10
[Social function] Impact on patient's ability to interact with people in a contextually and socially appropriate manner (eg, showing consideration and esteem when appropriate, responding to the feeling of others), to create and maintain close relationships with others (excluding members of the family), to engage in desired aspects of community social life (eg, charitable organizations, service clubs, or professional social organizations)10
Work Ability x x Worker ability to meet physical and/or psychological work demands10
[Sleep functioning] Sleep functions such as onset, maintenance, quality, amount of sleep, and functions involving the sleep cycle. This domain should also include the impact on perceptions of alertness and sleepiness during usual waking hours10
Quality of sleep/sleep disturbance because of pain x x x [not further specified]
Rescue medication/medication intake A medicine administered to relieve an acute exacerbation of a condition (eg, asthma and migraine) that is normally controlled with prophylactic medicine (https://medical-dictionary.thefreedictionary.com/rescue+medication; last access: 18/06)
Sedation x x
Analgesic requirements x [not further specified]
Analgesia (use) x x
Consumption of rescue analgesia x x x
Analgesic efficacy x
Cumulative analgetic consumption x x
Postoperative opioid analgesia x
Morphine consumption x x x
Infused anaesthetic volume x
Time to first analgesia/duration of analgesia/first analgesic requirement x x
Amount of supplemental pain medication x
Amount of demanding dose x
Frequency of additional NSAID administration x
Intraoperative anesthetic agent requirements x
Intraoperative opioid requirements x
Frequency of narcotic administration x
Number of regional anesthesia bolus top-ups x
Total bolus volume x
Morphine equivalent dose x
Infused anesthetic volume x
Quality of analgesia x x
Satisfaction x x x Patient's satisfaction with care received, including treatment and care providers10
Participants ratings of global improvement and satisfaction with treatment x
Patient Comfort x [not further specified]
Resource use/Economical impact Economic impact of health conditions both on society and on the individual. Both the presence of a health condition and its treatment incur resource use4
Cost x [not further specified]
Hospital stay x x x [not further specified]
PACU stay x
Length intervention x
Length of stay in the ICU (discharge from the ICU and readiness of discharge from the ICU) x
Duration of analgesia x
Pathophysiological manifestations … whether or not the effect of the intervention specifically targets the pathophysiology of the health condition. […] this area also encompasses all biomarkers and surrogate outcomes4
Discomfort General x [not further specified]
Chest x
Physiologic response x x [not further specified]
Hyperalgesia (by QST) x
Vital signs x
Pulmonary complications x
Spontaneous respiratory rates x
Time to ventilation weaning/time of extubation x
Duration of mechanical ventilation x
Oxidative stress x
Stress hormone plasma concentration x
Troponin I/CK-MB/pBNP levels x
Time to eye opening x
Side effects x x x Unintended negative features or consequences of an option. These can be temporary or permanent and major or minor. Descriptions of harms and side effects should include how severe the negative effect will be, how long it might last, and how often someone can expect to experience the negative effect. An example of harm is the development of breast cancer from taking estrogen and progesterone. An example of a side effect is upset stomach from taking an antibiotic pill37
Adverse events x* *IMMPACT Recommendation13,45: passive capture of spontaneously reported adverse events and symptoms and use of open-ended prompts
Surgical adverse events x
Medical adverse events x
Motor dysfunction (eg, motor block) x
Sensory dysfunction (eg, nerve or sensory block) x x
[renal dysfunction](eg, creatine clearance/serum creatine) x
Other domains:
Participant Disposition x*
Concentration of local anesthetics or opioid plasma level x
Subfertility x
Complications x x
BS, breast surgery; ES, endometriosis surgery; ST, sternotomy; TKA, total knee arthroplasty.
*IMMPACT recommendations had been assumed appropriate for standardizing outcome assessment for endometriosis, partially by indicating IMMPACT recommendations of outcome measures.

2.4. General information for participants

All participants received a written handbook with introductory texts regarding the aim, scope, and agenda for the meeting, definition, and explanation of the relevant terminology of COS development (core outcome set, COMET, OMERACT, patient-reported outcome, and similar ones) along with the definition of the identified outcome domains by SLR a priori to the meeting. Definitions and abbreviations of the most important constructs and initiatives are presented in supplement digital content 7, available at http://links.lww.com/PAIN/B320.

At the meeting, introductory lectures were given in accordance with the handbook and aim of the meeting. Because the patient representatives were experienced with the processes and terminologies, a specific patient preparation meeting was not scheduled. Throughout the meeting, 3 issues were on display, ensuring participants kept these in mind:

  • (1) The scope of the meeting (see the Introduction).
  • (2) The understanding of therapy aims (lay definition): as general objectives of acute pain management related to surgery focusing on restoration of impaired (psychological and/or physical) function and the reduction of suffering because of postoperative pain considering a patient-centered approach, as well as the risks and benefits associated with the interventions within the first weeks after surgery.
  • (3) The rules of the meeting: the aim is to achieve a consensus on the WHAT TO MEASURE for the above-described scope speaking as a representative of a stakeholder group, not an individual person.

2.5. Performing the consensus process

The consensus process (step 2, Fig. 1) was held during a 1-day face-to-face meeting (June 2018, Berlin). The meeting schedule is provided in Figure 2, displaying a flexible approach consisting of plenary group sessions (all panel members) and breakout groups (surgery-related groups), introduced by a small exercise to establish an understanding as a representative of a specific stakeholder group. The process was facilitated by 2 members of the steering committee (E.P.Z. and U.K.) during plenary group discussions and by 4 other members of the steering committee for breakout groups (W.M., P.Z., H.L., and C.W.). The 2 plenary meetings in between, reporting on preliminary results of surgery group discussions, should enhance transparency of the process between the breakout groups, information flow, and preparing a plenary group consensus discussion.

Figure 2.
Figure 2.:
IMI PROMPT schedule for recommending the core outcome set of domains for perioperative pain management after surgery. The consensus process was performed within a 1 day meeting and facilitated by the steering committee members. Thirty-eight stakeholders (9 stakeholder groups and patient representatives) participated in the consensus process. The main part of the meeting consisted of a specific stakeholder group session (not shown), world café (surgery related groups), and breakout sessions (discussing and prioritizing therapy aims [“balloons”], and domains [“puzzles”] and mapping of therapy aims to domains) as well as plenary group sessions in between. The final plenary session decided on those domains taken into voting; voting was performed at the end of the meeting. Details of the complete process conduction are reported in the Method section. PROMPT, Providing Standardized Consented PROMs for Improving Pain Treatment.

Initially, after introducing all participants to the aim, rules, and background of the meeting (Fig. 2), patient representatives and all other stakeholder groups were invited to align on a shared perception of their roles as a stakeholder before discussing content. The results were presented to the plenary group to set expectations, fears, and wishes obvious to everyone and to create an open minded and respectful atmosphere. Throughout all steps, the IMI PROMPT consensus panel was encouraged to structure therapy aims or domains either into general regarding perioperative pain management or into more specific regarding perioperative pain management of the 4 surgeries.

Identification and prioritization of therapy aims for perioperative pain management, the first step of the consensus process (Fig. 2, preparation of material), was discussed and supported by several visualization techniques (world café for introduction and ensuring multiple perspectives, guided group discussion by decision scale and providing theoretical framework, and OMERACT filter 2.0). During the consolidation process (world café), all surgery groups attended each surgery wall, discussing and leaving as much input as they considered necessary to be comprehensive in identifying relevant therapy aims later and establishing a hierarchy.

Finally, the surgery groups were advised to prioritize the a priori defined therapy aims, completed by a presentation and discussion in the plenary group.

During the second part (Fig. 2: identification and voting), initial outcome domains for each of the surgeries were mapped to the prioritized therapy aims. The surgery groups were invited to map the aims with outcome domains indicated by the a priori conducted systematic reviews. In case of missing outcome domains from the systematic search, the participants were advised to form new ones. The results of the discussions were displayed on pin walls analogous to the previous steps, whereby the OMERACT filter 2.0 core areas were replaced by the main aim areas from the preceding discussions.

A small group meeting (presentation and discussion of all small-group results after each step) ensured transparency between the groups and comparison of the different perspectives. Feedback was then taken back into the surgery plenary group discussions.

In the case of complete disagreement with a single outcome domain, when achieving a unanimous opinion against a decision of other stakeholder groups, patient representatives were able to veto. If another stakeholder group consistently disagreed with a panel decision, it was invited to advise the panel to discuss the issue again. In the case of disapproval of discussing an outcome domain again, further discussion was planned to be dismissed, and the group was invited to move forward to the next outcome domain.

2.6. Scoring of outcome domains

Scoring for outcome domains was not applied because of the quality of reporting outcome domains.

Prioritization was supported by the OMERACT 2.0 filter37 in providing core areas, and a scale from 1 to 3 (not important), 4 to 6 (important but not critical), and 7 to 9 (critical) displayed on pin walls throughout the meeting. All therapy aims and outcome domains were provided on cards to be sorted to both the core area and the importance according to the 1 to 9 scale. The panel members were advised to find at least one outcome domain for each of the core areas. In the case of no relevant outcome domain for one core area, they had to explain why they would like to omit that specific core area. During the presentation of each surgery in the plenary group, an overall perspective (general aims and/or outcome domains) was supported simultaneously and displayed in the same way by the facilitators. In case of competing outcome domains within one therapy aim, the panel approved the outcome domain most frequently mapped and dropped the less important outcome domain.

Inclusion of outcome domains required an outcome domain to be rated as at least a 7 on the 1 to 9 rating scale for further consideration.

2.7. Consensus definition

Consensus on outcome domains (presence meeting) was defined as at least ≥70% voting for 7 to 9 and ≤20% voting for 1 to 3 rating (meaning that most of the panel felt that the specific outcome domain was important to include) by the complete panel to include an outcome into future COS (Table 3). Exclusion was defined as 70% of voting for 1% to 3% and 20% voting for 7 to 9 for a certain outcome domain. All other cases were considered no consensus, which meant that there was uncertain evidence about the importance of the specific outcome domain to be included into future COS.

Table 3 - Definition of consensus for PROMPT consensus on outcome domains and measurement instruments regarding perioperative pain management in patients after surgery (BS, TKA, ST, and EM).23
Consensus classification Description Definition
Consensus “in” Consensus that either outcome domain should be included into COS for perioperative pain management after surgery (BS, TKA, ST, and EM) 70% or more participants scoring 7-9 and 20% or less participants scoring 1-3
Consensus “out” Consensus that either outcome domain should not be included into COS for perioperative pain management after surgery (BS, TKA, ST, and EM) 70% or more participants scoring 1-3 and 20% or less participants scoring 7-9
No consensus Uncertain about importance of outcome Anything else

2.8. Ethics and consent

The methods and procedures of the study were developed in compliance with the ethical principles of the Declaration of Helsinki and Good Epidemiologic Practice and were approved by the Ethical Committee of TU Dresden (EK 261052019). The process is described as a consensus process, including patients who were nominated by representatives of official organizations (self-help organizations) and therefore represent the interests of those organizations. No treatment was offered, and patients were not harmed. All data of all participants were gathered and analyzed completely anonymously and at a group level.

3. Results

Relevant therapy aims for postoperative pain management after 4 specific types of surgeries.

Key issues during the discussion of therapy aims referred to functional aspects as well as to pain-related and, surprisingly, self-management–related aspects and led to a list of most relevant therapy aims for the specific surgical procedure (Table 4). The unsorted list of indications from the world café is provided as supplementary material (see Table, supplement digital content 8, available at http://links.lww.com/PAIN/B320).

Table 4 - Prioritization of therapy aims for perioperative pain management for the 4 surgeries (TKA, ST, BS, and ES) and in general (Gen).
Rating criteria OMERACT Core Areas [4,37]
Life impact Pathophysiological manifestations
TKA ST BS ES Gen TKA ST BS ES Gen
9 {Acceptable/manageable pain at movement} {Functional impairment} {Aspects of Quality of life} well informed empowered patients {Restoration of function [dot]} {↓ pain}   {To facilitate early mobilization} {Low-pain Intensity} {Severe adverse events from pain intervention} {Pain relief [dot]} {↑function: -visceral, -physical, -sleep}
8 {Acceptable/manageable pain at rest}   {Empowering the patient to self-management [dot]} {↓ psycho-social distress (anxiety, catastrophizing, fear)}   {Restore activity of daily living*} *relevant for the first two weeks   {Prevention of chronic pain}
7 {Minimize emotional distress}   {Pain*}     {Promote quality + duration of sleep}   {Function* procedure specific}
6 {↑self-care/man[a]gement} {self-management}
5 {To facilitate early discharge}
4
3
2
1
Issues to consider Quality of life within 2 weeks after surgery postoperative recovery (scale) Systematic documentation of date Tailored provision of information to set realistic expectations Predictive factors of C[hronic] P[ain] Follow-up after discharge of symptoms, pain, and side effects
Rating criteria
Resource use/Economical impact Death Adverse effects
TKA ST BS ES Gen TKA ST BS ES Gen TKA ST BS ES Gen
9   [actively crossed out]         [actively crossed out]     {to reduce postop[erative] complications/adverse events/costs}   {minimize side effects + adverse effects [dot]} {↓ adverse effects}  
8 [actively crossed out] [actively crossed out]
7     [actively crossed out]       {low death rate} [actively crossed out]             {Adverse events*}
6 {Cost-effectiveness}
5
4 {↓Hospital stay}
3
2
1
Issues to consider Rational/appropriate analgesic use Death needs to be reported, not to be an outcome to consider different approaches in high/low pain responders benefits vs risks surgery vs P[ostoperative] P[ain] M[anagement] complications
Results from the break out groups: TKA: total knee arthroplasty, BS: breast surgery, ST: sternotomy, ES: endometriosis surgery. Results from the plenary group: Gen general outcomes. {…} complete entities indicated by participants. […] within one word: additions of abbreviations by the authors. [dot] indicated as most important by participants.
*Subsumed domains introduced after discussing results from the break out groups (common denominator suggested by participants).

To enhance decision-making, a scale from 1 (not important) to 9 (critical) was displayed together with the OMERACT filter 2.0 core areas. For the core area life impact, the main aims for the surgery groups consisted of pain-related constructs, functional aspects, self-management, and empowerment, as well as emotional factors such as distress. The need for systematic documentation, the choice of the appropriate time span for assessment, the consideration of quality of life aspects, and the patient-centered information (tailored and need specific) were important aspects that the panel wanted to share.

For the core area pathophysiological manifestations, both functional aspects (restoration of functioning and enabling of early mobilization) and pain-related aspects (pain relief, prevention of chronic pain, and avoiding side effects from pain medication) were emphasized. For the core area resource use/economical impact, very few aims were suggested (primarily, hospital stay and cost-effectiveness), as were the same with the core area death with only one nomination (low death rate) rated as being critical. One surgery group had actively crossed out the core areas of resource use/economical impact and death, indicating that they did not consider either core area of importance in their field of interest. The domain adverse events was highly praised for relevance in perioperative pain management studies throughout the groups.

During the plenary group discussion, the participants prioritized on 4 main areas of therapy aims regarding perioperative pain management after the 4 specific surgeries: function, pain, AEs, and self-management. Those areas were taken to the next step in identifying, discussing, and advising relevant outcome domains for the future core outcome set by each surgery group. Finally, the plenary group decided that the core area death was not a relevant core area for investigating perioperative pain management after surgery. Other issues were highlighted for further considerations in designing clinical trials (sometimes motivated by therapeutic perspectives) containing the definition of an appropriate time span, considering predictive factors for developing chronic pain, a more detailed understanding of rational or appropriate analgesic use, and different approaches regarding high-pain or low-pain responders to sufficiently consider those aspects in future clinical trials. The careful balancing between benefits and risks of perioperative pain management interventions for correct representation of AEs was raised as well.

3.1. Mapping therapy aims and outcome domains

The summary of the surgery groups and the general agreement is shown in Table 5. Regarding the main aim area AEs, all groups rated aligned outcome domains as of highest importance (≥7 on the rating scale). Two groups emphasized again that only AEs related to pain management should be considered. For pain, pain intensity was consistently recommended as the highest priority, whereas the operationalization of the outcome domain differed between the groups. Function as a main aim area was consistently operationalized as physical function (of highest priority), highlighted by the necessity to assess function specifically for the affected body location of the surgery, eg, functional impairment because of pain. Emotional or psychological aspects of function (emotional distress and emotional and cognitive function) were rated with slightly subordinate relevance voting as critical, and others rated those outcome domains of importance but not of critical relevance. Sleep was mentioned as well as important but rather less relevant than the domains described above. For self-management, it was obvious that the groups were challenged deriving an outcome from the previously therapy aims identified earlier. Although self-management was strongly discussed, the lack of outcome domains from the systematic research significantly hampered finding a suitable construct. Several aspects were discussed, and the groups differed in detailed operationalization from therapy aim to outcome domain (Table 5). Coping, (pain) expectations, health literacy (reported as knowledge/being and the status of being well informed), and skills/strategies and self-efficacy were taken into account and finally advised to be considered further. The plenary group finally decided to vote for one overarching core outcome set because they, early in the process, realized that the most important outcome domains are similar for all 4 surgery groups regarding the perioperative pain management in clinical trials. A general COS was, therefore, aimed for, but already having in mind, that the operationalization of the future measurement must be condition-specific for the underlying impairment because of the form of surgery.

Table 5 - Therapy aims and outcome domain mapping domains and operationalisation from the therapy aim prioritization in step 4.
Rating criteria TKA ST BS ES Gen
Adverse events
9 Complications side effects Adverse events during study Side effects potentially related to pain management Symptoms and adverse events—side effects of pain medication Postoperative complications
8 Adverse events
7 Side effects
6
5
4
3 Complications from surgery (Death needs to be reported, not to be an outcome)
2 Participants disposition (incl adherence, withdrawal) Benefits vs risks
1 Surgery vs P[eri] O[perative] P[ain]M[anagement]
Issues to consider Quality of life within 2 wk after surgery; postoperative recovery (scale) Systematic documentation of date Tailored provision of information to set realistic expectations Predictive factors of C[hronic] P[ain]
Pain*
9 Pain intensity during activity (trajectory) Acceptability of the pain
Pain intensity + quality
Pain intensity at rest + during activity during a certain time span in surgical area related Pain
intensity
Location
Impact/interference
Temporal pattern
Pain quality (eg, nociceptive and neuropathic)
Pain intensity
8 Pain intensity at rest (trajectory) Pain characteristics Pain intensity during activity condition specific
7 Consumption/need of rescue analgesics   Pain intensity at rest
6 Consumption of rescue analgesia Acceptability of pain
5 Opioid consumption Pain quality
4
3
2
1
Issues to consider Follow-up after discharge of symptoms, pain, and side effects
Function*
9 Physical function for knee (early) mobilization [Function] Physical psychological social Restoration of physical function (upper limp) daily activities Functioning physical functioning
Daily activities
Sleep
Mobility
Organ/visceral function
Physical function (procedure specific)
8 Psychological function
Emotional + cognitive f[un]ct[ion]
Emotional distress Emotional distress
7 Sleep function (duration + quality) Emotional function
6
5 Satisfaction concerning pain treatment sleep function Psychological function Emotional functioning
Catastrophizing
Fear
Anxiety/stress
Body image/self esteem
4  
3
2
1
Issues to consider Reconsider self (care) management maybe a process variable
Self-management
9 Fully informed consent (really empowered patient) Self-management may include knowledge skills self-efficacy*
[restoration of function]*
Pain self-management + strategies—self efficacy—coping
8 Pain expectations/knowledge
[Acceptable/manageable pain at movement]*
Social support [↓ psychosocial distress (anxiety, catastrophizing, and fear)]* Self-efficacy
7 [Empowering the patient to self-management]* [↑self care/man[a]gement]* Pain expectations
6
5 [To facilitate early discharge]* Cost-effectiveness [↓Hospital stay]*
4
3
2
1
Issues to consider To consider different approaches in high/low-pain responders But how to measure in a standardized way?
Health-related quality of life*
Rational/appropriate analgesic use Death needs to be reported, not to be an outcome
Results from the break out groups: TKA, total knee arthroplasty; ST, sternotomy; BS, breast surgery; ES, endometriosis surgery. Results from the plenary group: Gen general outcomes. […] within one word or otherwise in the table: additions of abbreviations by the authors. 1-3 not important, 4-6 important but not critical, 7-9 critical.
*Therapy arms with no mapping outcome domain from SLR.

Thirteen outcome domains (displayed in Table 5 under General, rated between 7 and 9) were finally taken into voting on a COS for perioperative pain management.

3.2. Consensus on outcome domains

The results from the final voting are presented in Figure 3. Participants of all stakeholder groups (N = 35) voted for the COS for perioperative pain management.

Figure 3.
Figure 3.:
Final voting on core outcome domains for perioperative pain management by the IMI PROMPT panel participants across all surgeries. Rating scale: 1 to 3 not important; 4 to 6 important, but not critical; and 7 to 9 critical. Inclusion into the core outcome set: 70% or more of the panel rated the domain between 7 and 9 and less than 20% rated the same domain between 1 and 3; Exclusion from core outcome set consideration: 70% or more if the panel rated the domain between 1 and 3, and less than 20% rated the same domain between 7 and 9. The vertical red line indicates the cutoff for inclusion, and the finally included domains are highlighted in the dark box. PROMPT, Providing Standardized Consented PROMs for Improving Pain Treatment.

Five outcome domains were rated as core outcome domains (according to the consensus rules): physical function (100% agreement), pain intensity during activity (84% agreement and 0% disagreement), AEs (80% agreement and 0% disagreement), pain intensity (77% agreement and 3.5% disagreement), pain intensity at rest (73% agreement and 0% disagreement), and self-efficacy (70% agreement and 13% disagreement).

After defining consensus on COS domains, the steering committee has aligned on definitions (especially for self-efficacy because this domain was not provided by the initial list of outcomes) and necessary adaptations of all definitions for the future context of use. The final definition of those outcome domains is summarized in Table 6. Although the core domains are considered relevant to any perioperative pain management intervention after any surgery, the assessment must consider condition-specific aspects when measurement instruments will be defined, eg, for physical function.

Table 6 - Definitions of the final IMI PROMPT COS domains.
Domain Definition of domain
Pain intensity Pain intensity is defined as how much a person hurts, considering the overall magnitude of the [sensoric aspect of the] pain experience (modified according to10)
Pain intensity at rest after surgery is defined as how much a person hurts, considering the overall magnitude of the [sensoric aspect of the] pain experience during no activity after surgery (eg, lying in bed); (modified according to10 and44)
Pain intensity during activity after surgery is defined as how much a person hurts, considering the overall magnitude of the [sensoric aspect of the] pain experience that is brought on or aggravated by a defined activity (modified according to10,44)
Pain-related physical function after surgery … is defined as one's ability to carry out various activities that require physical capability while experiencing acute postoperative pain (adapted from7)
Pain-related self-efficacy after surgery …is defined as the extent or strength of one's belief in one's own ability to complete tasks while experiencing acute postoperative pain (adapted from2)
Adverse events (adverse reaction; synonyms: adverse drug reaction (ADR), Suspected adverse (drug) reaction, adverse effect, and undesirable effect) A response to a medicinal product which is noxious and unintended [DIR 2001/83/EC Art 1(11)1].
Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility (see Annex IV, ICH-E2A guideline).
Adverse reactions may arise from the use of the product within or outside the terms of the marketing authorization or from occupational exposure [DIR 2001/83/EC Art 101(1)]. Conditions of use outside the marketing authorization include off-label use, overdose, misuse, abuse and medication errors.
See also adverse event, serious adverse reaction, unexpected adverse reaction, off-label use, overdose, misuse of a medicinal product, abuse of a medicinal product, and occupational exposure to a medicinal product14

3.3. Deviations of IMI PROMPT panel recommendations regarding common outcome assessment of effectiveness of perioperative pain management

Besides the endorsement of common outcome domains for comparative research in perioperative pain management and acute postoperative pain (pain intensity, physical function, and AEs; refer to Table 2) a new outcome domain had been identified, critical for inclusion into a COS for perioperative pain management. This process might need some further explanation. Starting with brainstorming in step 4 (world café, see Table, supplement digital content 8, available at http://links.lww.com/PAIN/B320), psychological aspects have been initially indicated, such as psychological function, self-management, empowerment, fear of movement and other anxieties, self-care, or well-informed patients. In discussion about relevant therapy aims within the surgical breakout groups, some of these variables were highly prioritized by 7 to 9 (on a scale 1-3 not important, 4-6 important but not critical, and 7-9 critical), including emotional distress, empowerment to self-management, psychosocial distress (anxiety, catastrophizing, and fear), restoration of activity of daily living, and aspects of quality of life (Table 4). It was apparently in contrast to the initial list of outcomes (Table 2), where few psychological aspects were assessed in clinical trials at this stage, comprising fatigue, relaxation, emotional distress, anxiety, agitation, and cognitive function. By discussing existent outcome domains from the initial list and their mapping to therapy aims (Table 5), the idea of a sufficient self-management of the patient after the specific surgery remained in the lists of all surgery breakout groups for patient empowerment (as completely consented); self-management including knowledge, skills, and self-efficacy; and pain self-management strategies and coping. The underlying idea was a patient returning to a minimum of self-management after surgery in maintaining daily and self-care activities, supported in feeling self-efficient, and therefore, less helpless, anxious, and dependent. Initially brought into discussion by nurses and patients, other stakeholders supported these aspects throughout all steps of this consensus process, forming self-efficacy out of different aspects of psychological variables. The importance of psychological parameters for comparative effectiveness research in perioperative pain management and acute postoperative pain was highlighted by 4 additional outcome domains recommended for final voting (Fig. 3; such as emotional function, pain expectations, acceptability of pain, and emotional distress), all missing the rules of being voted out (Fig. 3). Especially emotional distress, the only psychological variable also included into the initial list of outcomes (Table 2) only closely missed the rule of being included into the final COS. This much refers to the fact that perioperative pain management rather enables patients to be confident to return to their previous activities in controlling the pain (self-efficacy), compared with emotional distress which might be addressed rather by clear psychological interventions.

4. Discussion

The aim of this project was to develop a core outcome set of domains for effectiveness and efficacy in clinical trials, observational studies, and clinical practice regarding perioperative pain management in adult patients undergoing TKA, ST, BS, and ES. A panel of 10 stakeholder groups, including patient representatives, recommended 5 overarching outcome domains for perioperative pain management, in general, comprising physical function (condition-specific), pain intensity at rest and during activity, AEs, and self-efficacy. All 5 domains received more than 70% agreement with less than 20% disagreement, indicating that they were relevant to most invited stakeholders and should therefore be considered the core outcome domain.

Starting from the relevant therapy aims, some main clusters of aims of effective perioperative pain management were consistently indicated by all groups of surgical procedures: reduced pain at rest (to enhance for example sleep and wellbeing) and during activity (to improve early mobilization), leading to early and, also later, improvement of physical and emotional function. Furthermore, the enabling of patients towards greater self-empowerment and self-management postoperatively regarding their pain management, and to a reduction of additional medication and side effects and AEs, was felt to be relevant by the participants.

The high relevance of maintained or improved self-management postoperatively was indicated by patients and nurses and consistently followed during all steps, so the inclusion of the domain self-efficacy into the IMI PROMPT domain COS was stringent and logical. Several other psychological domains arose from the first 2 steps (brainstorming and therapy aims), such as satisfaction, emotional functioning, acceptability of pain, and/or emotional well-being. Another psychological construct, emotional distress, closely missed the 70% rule of inclusion into COS. The fact that those concepts were discussed intensively and that almost 2 psychological constructs got advised to be critical by the panel highlights the need for considering psychological aspects also in the setting of perioperative pain management. This implies that psychological variables are more important than considered so far and should complete outcome assessment as secondary outcome beyond a core outcome set in studies. Interestingly, outcome domains for important aims regarding psychological aspects were underreported in previous clinical trials so far, as observed during the systematic reviews before the meeting. This leads to the assumption that such outcome domains, considered of high relevance for patients, have not been acknowledged sufficiently in previous perioperative pain management studies; this aspect in general was suggested by others27 but not yet defined together with patients. Thus, we expect the current COS to be closer to patients' actual needs and expectations of effective perioperative pain management. We defined self-efficacy according to common definitions but are currently realizing (by searching for PROMs able to assess this domain) that the common understanding of self-efficacy is diverse; thus, an important future step will be to ask patients what such terms (eg, self-efficacy and emotional distress) mean in the context of postoperative pain experiences and how it can be assessed by using appropriate PROMs (next step25). Aspects of self-efficacy discussed by the panel rather touched tasks of self-sufficiency, considering the clinical context of perioperative pain management and natural limitation in functionality after surgery.

Also important was a preference for pain intensity during activity compared with pain intensity at rest after surgery, yet both included with a priority of evoked pain after surgery. The inclusion of both aspects of pain intensity (at rest and during activity) follows the considerations by other authors.19,27,44 Currently, different subdomains (pain intensity, pain intensity at rest, pain intensity during activity, and the kind of the inquired activity) are either not described or vary across clinical trials impeding interpretation and comparison of results from clinical trials.44 Clear differentiation between pain intensity at rest and pain intensity during activity as well as the use of validated PROMs to assess both domains will prevent inconsistency in outcome measures, enable differentiation between treatment effects related pain intensity at rest and during activity, and provide the base for evidence synthesis.38

The quality of perioperative pain management needs to control for its benefit and risk, so the domain adverse events was rated as critical and to be included in the future COS in addition to the other 4 domains. Pain after surgery can impair physical function leading to many other consequences such as delayed or even poor recovery.19 However, for example, after TKA, only 50% of clinical trials assessed aspects related to physical function. This Delphi panel voted the domain physical function with the highest priority, supporting that this domain should be assessed with highest priority to assess effectiveness on perioperative pain management. Yet, because of the different surgical procedures and thus the corresponding impaired function of different body parts, different tissues involved, and—most importantly—different secondary aims of sufficient pain management (eg, improved breathing after ST vs improved walking steps after TKA), the need to assess physical function specific to the type of surgery was emphasized.

To the best of our knowledge, most other active COS initiatives focus specifically on the treatment of chronic pain conditions, on the surgical intervention of one of the specific body locations we were addressing, or on the disease without a focus on pain.3,6,12,24,30,31,33,34,39–41,47,48 Our results are partially in line with other recent recommendations for COS in clinical trials investigating treatment effects for complex regional pain syndrome by COMPACT, for standardized endpoints in perioperative medicine by StEP, and for single-dose analgesic efficacy trials in acute pain by IMMPACT.11,22,35 Reasons for discrepancies might be due to a different scope of the COS as well as substantial differences in methods of performing such processes, such as the patient involvement and the stepwise, multifaceted approach as advised by COMET. A gold standard of performing COS consensus processes is still lacking,21,50 and COS recommendations should not be mistaken as a final, unquestionable status instead of being a current and dynamic alignment of protagonists requiring updates and advances.42,50 Furthermore, the inclusion of patients' perspectives obviously shapes future recommendations but are not included in many initiatives.1,9,36,51 Despite the situation, that transparency of stakeholder groups' composition, describing at least a few characteristics of the participants, is recommended,28,29 but unfortunately, it is not always provided. As the broadness of interests and backgrounds enhanced the discussion and brought up many additional aspects (especially, the psychological issues), the indicated aspects obviously depend on experience and background of each participant. Comparison of our results, especially regarding the differences to similar recommendations, is therefore limited because descriptions of other panels have not been reported in detail.35

Harmonizing outcome assessment requires a minimum set of relevant outcome domains, and our consensus process described here is one step towards this process related to acute postoperative pain.25 Five outcome domains are a clear minimum and in line with OMERACT recommendations.4 This enables researchers to add specific outcome domains for their particular study aims, increase acceptance by future consumers, and help in harmonizing outcome assessment on a realistic minimum level. Feasibility might be increased by the fact that the IMI PROMPT core outcome domains were not considered procedure-specific (independently of the condition-specific assessment by future PROMs). Eventually, it should to be determined whether there is a need for more detailed outcome (sub)domains at a lower level. Otherwise, it is, of course, possible to add specific outcome domains according to the detailed aims of clinical trials and their individual purposes. However, improving specification of pain intensity assessments and adding PROMS for physical function and psychological aspects such as self-efficacy in all future studies related to acute pain management will improve clinical relevance of the results, reduce reporting bias in studies, enable comparison between study results, and enhance evidence-based recommendations in the field of acute postoperative pain management.

Several issues arose from the discussions regarding the definition of an appropriate time span, considering predictive factors for developing chronic pain, a more detailed understanding of rational or appropriate analgesic use, and different approaches regarding high-pain or low-pain responders to sufficiently consider those aspects in future clinical trials. In addition, the careful balancing between benefits and risks of perioperative pain management interventions for correct management of AEs was brought up. Despite the fact that those issues do not affect the core outcome set of domains, they need to be considered for identification and/or establishment of a corresponding core outcome measurement set, which constitutes the next step. The relevant time span of future assessment, for instance, will affect sensitivity and the choice of assessment times. The distinction between responders and non-responders might potentially guide the development of measurement instruments to ensure reliable interpretability of assessment results. In addition to the main aim of identifying reliable and valid patient-reported outcome measures, the characteristics of pain, pain-related impairment, and recovery after surgery will be a challenge in both identifying relevant measurement concepts and estimating sensitivity of change by those measurement instruments, respectively.

Conflict of interest statement

E.M. Pogatzki-Zahn: During the last 5 years, E.M. Pogatzki-Zahn received financial support (to the institution) from Mundipharma and Grünenthal for research activities, personal fees for advisory and/or lecture activities and/or travel support from Grünenthal, MSD Sharp & DOHME, Mundipharma, Janssen-Cilag, Fresenius Kabi, Novartis, and AcelRx, and research grants (to the institution) from BMBF, DFG, EU, and Innovationsfond Germany, all outside the submitted work. H. Liedgens: H. Liedgens is an employee of Gruenenthal GmbH. WM: W. Meissner received grants from Pfizer and Mundipharma, grants and personal fees from Grünenthal, and personal fees from TAD, BioQPharm, Bionorica, Kyowa, Northern Swan, and Tilray, all outside the submitted work. K. Vincent: During the last 5 years, K. Vincent received research funding from Bayer Healthcare and Honoraria and travel support for consultancy and/or lectures from Bayer Healthcare, Grunenthal GmbH, AbbVie, and Eli Lilly, all outside the submitted work. R.-D. Treede reports grants from Bayer, personal fees from Grünenthal, GSK, and Bayer Sanofi, and grants from EU, DFG, and BMBF, outside the submitted work. U. Kaiser received lecture fees and travel support from Grünenthal and Mundipharma during the past 5 years and research funding from BMBF, DFG, and Innovationsfonds, all outside the submitted work. The remaining authors have no conflicts of interest to declare.

The statements and opinions presented here reflect the authors' views, and neither IMI nor the European Union, EFPIA, or any associated partners are responsible for any use that may be made of the information contained therein.

Appendix A. Supplemental digital content

Supplemental digital content associated with this article can be found online at http://links.lww.com/PAIN/B320.

Acknowledgments

The authors thank all members of the IMI-PainCare PROMPT consensus panel including (in alphabetical order) Alexander Avian (Medizinische Universität Graz, Institut für Medizinische Informatik, Statistik und Dokumentation, Graz, Austria), Patric Bialas (Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum des Saarlandes, Homburg, Germany), Didier Bouhassira (Inserm U987, APHP, UVSQ, Paris-Saclay University, CHU Ambroise Paré, Boulogne-Billancourt, France), Susan Broekmans (Leuven Center for Algology and Pain Management - Nursing Center of Excellence, University Hospital Leuven, Belgium), Karoline Buhre (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Bonn, Germany), Rebecca Chandler (School of Allied Health, Faculty of Health, Education, Medicine & Social Care. Anglia Ruskin University, Cambridge, United Kingdom), An DeGroef (Department of Rehabilitation Sciences, KU Leuven—University of Leuven, Leuven, Belgium; and Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium), Alaine Delve (Plevic Pain Support Network, United Kingdom), Klaus Döbler (KCQ—Kompetenzzentrum Qualitätssicherung/Qualitätsmanagement, Stuttgart, Germany), Dominique Fletcher (Service d'Anésthesie, Hôpital Ambroise Paré, Boulogne Billancourt, France), Axel Forman (Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark), Manela Glarcher (Paracelsus Medical University, Institute of Nursing Science and Practice, Salzburg, Austria), Hakim Harkouk (Département d‘Anesthésie, INSERM U987, CHU Ambroise Ambroise Paré, Boulogne-Billancourt, France), Lone Hummelshoj (Endometriosis.org, United Kingdom; World Endometriosis Society, Vancover, Canada; World Endometriosis Research Foundation, London, United Kingdom), Magdalena Kocot-Kępska (Department for Pain Research and Treatment, Medical College Jagiellonian University, Krakow, Poland), Albère J.A. Köke (Department of Rehabilitation Medicine/CAPHRI, School for Public Health and Primary Care, Maastricht University, NL; Adelante Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, NL; and Zuyd University for Applied Sciences, Faculty of Health and Technology, Heerlen, NL), Michael Koller (Center for Clinical Studies, University Hospital Regensburg, Germany), Britta Lambers (University of Applied Sciences Fresenius, Dept. Health & Social, Cologne, Germany), Alexandros Makri (Department of Anaesthesiology, Asklepieion Hospital of Voula, Athens, Greece), Tuomo Meretoja (Breast Surgery Unit, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland), Niamh Moloney (THRIVE Physiotherapy, Grande Rue, St. Martins, Guernsey, Channel Islands; and Faculty of Medicine, Health & Human Sciences, Macquarie University, NSW 2109, Australia), Paul Nilges (Johannes Gutenberg-Universität Mainz, Weiterbildungsstudiengang Psychotherapie, Mainz, Germany), Heike Norda (Pain Patient Organisation UVSD SchmerzLOS e.V., Lübeck, Germany), Madelon Peters (Maastricht University), Daniel M. Pöpping (Department of Anesthesiology and Intensive Care, University Hospital Muenster, Germany), Alexander Schnabel (Department of Anesthesiology and Intensive Care, University Hospital Muenster, Germany), Audun Stubhaug (Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway; and Faculty of Medicine, University of Oslo, Oslo, Norway), Regina van Boekel (Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Center, Nijmegen, The Netherlands), Dimitri van Ryckeghem (Institute for Health and Behaviour, Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Experimental Health Psychology and Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands; and Department of Experimental-Clinical and Health Psychology, Ghent University, Ghent, Belgium), Katy Vincent (Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom), Harriet Wittink (Utrecht University of Applied Sciences, Research Centre Health and Sustainable Living, Lifestyle and Health Research Group, Utrecht, NL), and Sigríđur Zoega (Pain Services, Landspítali - The National University Hospital of Iceland, Reykjavík; Iceland). The authors thank Daniel Segelcke, University Hospital Muenster, for creating all figures in this manuscript. The authors thank Marcus Komann for his contribution to meeting organization and discussions. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [777500]. This joint undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA (www.imi.europa.eu; www.imi-paincare.eu).

Author contributions: E.M. Pogatzki-Zahn and H. Liedgens led the project presented here. They, together with U. Kaiser, have developed the aim of the project and drafted the article. P. Zahn, E.M. Pogatzki-Zahn, H. Liedgens, and U. Kaiser have further developed the protocol for the systematic reviews. U. Kaiser and E.M. Pogatzki-Zahn have developed the concrete rationale for the consensus processes. E.M. Pogatzki-Zahn and U. Kaiser have drafted, coordinated, and mainly contributed to the writing of the article. W. Meissner, K. Vincent, L. Hummelshoj, R.-D. Treede and C. Weinmann have contributed to the development and organization of the process and have contributed to the article. E.M. Pogatzki-Zahn and U. Kaiser revised the article, and R.-D. Treede, K. Vincent, and C. Weinmann contributed to the revision. All authors (and panel members) read and commented on the final and revised version of the article.

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      Keywords:

      Perioperative pain management; Core outcome domain set; Patient-reported outcomes; Postoperative pain; Consensus statement

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