Assessing outcome in postoperative pain trials: are we missing the point? A systematic review of pain-related outcome domains reported in studies early after total knee arthroplasty

Abstract

The management of acute postoperative pain remains suboptimal. Systematic reviews and Cochrane analysis can assist with collating evidence about treatment efficacy, but the results are limited in part by heterogeneity of endpoints in clinical trials. In addition, the chosen endpoints may not be entirely clinically relevant. To investigate the endpoints assessed in perioperative pain trials, we performed a systematic literature review on outcome domains assessing effectiveness of acute pain interventions in trials after total knee arthroplasty. We followed the Cochrane recommendations for systematic reviews, searching PubMed, Cochrane, and Embase, resulting in the screening of 1590 potentially eligible studies. After final inclusion of 295 studies, we identified 11 outcome domains and 45 subdomains/descriptors with the domain “pain”/“pain intensity” most commonly assessed (98.3%), followed by “analgesic consumption” (88.8%) and “side effects” (75.3%). By contrast, “physical function” (53.5%), “satisfaction” (28.8%), and “psychological function” (11.9%) were given much less consideration. The combinations of outcome domains were inhomogeneous throughout the studies, regardless of the type of pain management investigated. In conclusion, we found that there was high variability in outcome domains and inhomogeneous combinations, as well as inconsistent subdomain descriptions and utilization in trials comparing for effectiveness of pain interventions after total knee arthroplasty. This points towards the need for harmonizing outcome domains, eg, by consenting on a core outcome set of domains which are relevant for both stakeholders and patients. Such a core outcome set should include at least 3 domains from 3 different health core areas such as pain intensity, physical function, and one psychological domain.

Reply to Karlsen et al. Consensus on a core outcome set: a panel decision

“…The point you raised in your letter was an (in your view) missing outcome domain, namely, “opioid consumption.” We agree that this outcome domain is used very frequently in postoperative pain effectiveness and efficacy trials; as shown by us in our systematic literature research on domains assessed in pain studies after TKA and sternotomy, 1,5 analgesic consumption (as an umbrella term for opioid or analgesic consumption or rescue analgesia, among others) was the second most assessed outcome domain (assessed by more than 80% of the studies). The domain analgesic consumption was therefore certainly discussed by the panel during the consensus face-to-face meeting.…”

“…We are grateful for the letter from Karlsen et al, 4 that raised a very interesting point related to our previously published articles in PAIN. 1,6 Within these articles (and another one published recently by us as well 5 ), we systematically investigate outcome domains assessed in prospective interventional clinical trials regarding pain management after total knee arthroscopy (TKA 1 ) and sternotomy. 5 These data were consecutively used to develop a Core Outcome Set (COS) of domains referring to perioperative pain management after surgery in clinical trials, observational studies, and clinical practice by involving all relevant stakeholders, including patients.…”

“…The letter is directly related to the publication Bigalke et al, 2021. 1 The publication Pogatzki-Zahn et al, 2021 6 is part of the project IMI PainCare. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [777500].…”

Opioid consumption as a core outcome domain in postoperative pain management

“…Second, the Delphi process by Pogatski et al did not include representatives from sites in North or South America or Asia, although a major portion of analgesic trials is conducted there. 1,4 In recent years, the United States has focused on the opioid crisis, and had Americans been included in the Delphi process, the consensual core outcome set may have looked different. Third, Bigalke et al state that “analgesic consumption varies widely between patients without showing a clear association to the quality of pain management” with reference to a cross-sectional study investigating the association between pain intensity and desire for opioids.…”

“…We read with interest the article by Bigalke et al, 1 which is a review of reported outcomes in 295 trials on postoperative pain management after total knee arthroplasty. Along with 3 similar reviews on other types of surgery, this formed the list of potential outcomes in a subsequent Delphi process by Pogatski-Zahn et al, 5 leading to a core outcome set in postoperative pain management.…”