Prospect Methodology

Optimal recovery after surgery depends upon effective perioperative pain management. The PROSPECT (PROcedure-SPECific postoperative pain managemenT) initiative, a collaboration of anaesthesiologists and surgeons with broad international representation, provides healthcare professionals with practical, procedure-specific pain management recommendations, formulated in a way that facilitates clinical decision-making across all stages of the perioperative period. Recommendations are based on a systematic review and critical analysis of available procedure-specific evidence.

Methodology updates

In 2019, the PROSPECT methodology was modified to critically analyse the design of each study with regards to its relevance in current perioperative care practice. The process by which the recommendations are formulated was refined to take account of not only the quality of the available procedure-specific evidence, but also critical expert interpretation of the study design. The refined methodology was implemented for all procedure reviews performed from 2016 to August 2023. A detailed description of the methodology was published and is freely accessible: Joshi 2019.

In 2023, the PROSPECT methodology was further refined, as detailed in Joshi 2023. The PROSPECT Working Group (PWG) agreed to address several limitations and to implement new factors with the aim of adding rigour and transparency to developing the procedure-specific pain management recommendations. This update was implemented for PROSPECT reviews started from September 2023 onwards.

The most recent changes to the methodology are italicised in the sections below.

Once the procedure to be reviewed has been identified, a subgroup is selected which consists of at least two members of the PWG (including the subgroup lead). External members (i.e. non-PWG members) are invited to join a subgroup, if they have specific expertise in the surgical procedure to be reviewed. In addition, specialists in literature searches and/or data analysis, and research fellows may also be invited to assist with a particular project.

The subgroup’s role is to:

• Develop the protocol
• (2023) Register the review at an appropriate registry, such as PROSPERO
• Perform the initial literature search
• Review all the manuscripts to identify relevant studies for inclusion
• Assess the quality of included studies
• Create data tables
• Analyse the data and create summary evidence tables
• Evaluate the strengths and limitations of the included RCTs
• Draft the summary recommendations for presentation to the full PWG.
• (2023) For each recommendation, assign the level of evidence and the strength of recommendation using a modified GRADE approach.

The PWG subsequently examines, in detail, each analgesic, anaesthetic or surgical intervention recommended and not recommended by the subgroup. The PWG refines the recommendations, as necessary, and comes to a consensus agreement on all the recommendations, which are subsequently presented on the website.

The processes of performing the systematic review and formulating the recommendations are outlined below. For full details, please access the PROSPECT methodology publication: Joshi 2023.

• PROSPECT is supported by an unrestricted grant from the European Society of Regional Anaesthesia and Pain Therapy (ESRA).
• In the past, PROSPECT has received unrestricted grants from Pfizer Inc. (New York, NY, USA) and Grunenthal (Aachen, Germany).

• A systematic search for literature specific to perioperative pain management for the selected procedure is performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) recommendations.
• Several electronic databases are searched, including EMBASE, MEDLINE, PubMed and Cochrane Databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Abstracts or Reviews of Effects, Cochrane Database of Systematic Reviews).
• Broad search terms are used to reduce the risk of missing relevant publications. Search terms include words or phrases associated with specific procedures, possible interventions and pain-related outcomes.
• Reference lists of the relevant articles are manually screened to identify additional eligible studies that may have been missed in the initial literature search.
• The time period for the literature search for a new review is determined by the PWG, generally the preceding 10 years; for updates the period is usually 3–5 years from the end-date of the previous review.

• A priori defined inclusion/exclusion criteria are used to identify relevant randomised controlled clinical trials (RCTs).
• Review articles (e.g. systematic reviews, meta-analyses and umbrella reviews) assessing analgesic interventions for the relevant procedure are also identified.
  (2023) RCTs included in these publications are scrutinised for inclusion and will be analysed critically according to PROSPECT methodology.
• Criteria for inclusion/exclusion of RCTs:
  • Trials of analgesic, anaesthetic and operative interventions, published in the English language, addressing pain management related to the surgical procedure being reviewed.
  • Trials should report pain scores using a linear scale (e.g. visual analogue scale or verbal or numerical rating scale). For studies that do not include the raw data values of outcomes, data will be extracted from graphs and figures using plot digitisation software.
  • Trials of analgesic interventions should be included if they meet the inclusion criteria, regardless of whether basic analgesics (i.e. paracetamol and NSAIDs or COX-2-specific inhibitors) were administered.
  • Trials that report data pooled from patients undergoing mixed surgical procedures, from which no data tables are obtainable, are excluded.
  • (2023) Placebo-controlled studies in which the analgesic intervention of interest solely is paracetamol, NSAIDs, COX-2-specific inhibitors or opioids will not be included. Studies comparing one drug in a particular class with another in the same class will also not be included.
  • (2023) Studies should be prospectively registered on a publicly accessible clinical trials database and the study design, including the primary outcome in the registration, should coincide with that in the published study. However, if there are compelling reasons, the subgroup may decide to include a study that has not been prospectively registered. In such a situation, the reasons for inclusion must be documented.

• Two reviewers independently screen the titles and abstracts.
• Included studies then undergo full-text review and irrelevant papers are excluded.
• At any stage, in the event of disagreement between the two reviewers, the opinion of a third reviewer is obtained.
• A PRISMA flow chart is used to present the results of the search data, records screened, records excluded with reasons for exclusion, and studies included in the qualitative analyses.

• (2023) The previous approach to assessing the quality of the study and assigning levels of evidence and grades of recommendation will be replaced with the use of the Cochrane Collaboration risk of bias 2 tool (RoB 2) for the quality of reporting of methodology and results (Sterne 2019). The RoB 2 results will be published either in the manuscript or as a supplementary figure.
• For details of the study quality assessment process for PROSPECT reviews performed between 2016 and August 2023, click here

• Included studies are stratified by timing of the intervention (pre-operative, intra-operative or postoperative), and further categorised into the type of intervention: analgesic (systemic analgesics, analgesic adjuncts or regional analgesia techniques), anaesthetic or surgical.
• Summary information from the included studies is extracted and tabulated using a predefined data extraction form.
• Extracted information includes:
  • Study design (including interventions)
  • Population characteristics
  • Primary outcomes: pain intensity scores at rest or procedure-specific relevant movement. A change of more than 10 mm in pain scores is considered clinically relevant. (2023) Studies showing benefits on movement-associated pain will be considered preferentially over those showing benefits on pain at rest.
  • Secondary outcomes, evaluated as available, including: 24-h, 48-h, 72-h cumulative opioid requirements; time to first request for rescue analgesia; supplementary non-opioid analgesic use; opioid-related adverse events.
  • Clinical outcomes (e.g. type and incidence of postoperative complications; time to ambulation; hospital duration of stay), patient-reported outcome measures and treatment-related adverse effects will be noted when available.
• Meta-analyses may be performed if the studies are homogenous in the analgesic technique(s) utilised, with similar outcome measures that are reported or can be estimated as mean (SD) for continuous variables and proportions for dichotomous variables.
• For information about the qualitative and quantitative analyses prior to September 2023, click here

Development of draft recommendations

• The subgroup evaluates the strengths and limitations of the included RCTs (as explained below) and considers whether each intervention should be recommended or not.
• The proposed recommendations are circulated to all members of the PWG, together with the included studies and evidence table.
• Note that the basic analgesics, paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2)-specific inhibitors, are recommended for all surgical procedures. This concept has now been extended to include other simple, safe and inexpensive drugs and techniques with well-documented procedure-specific efficacy. For example, glucocorticoids and surgeon-administered local infiltration analgesia are recommended as basic analgesics for total knee arthroplasty (Lavand’homme 2022).

(2023) Modified Delphi approach

• The PWG members consider the strengths and limitations of the included RCTs (as explained below) and a modified Delphi approach is used to determine the consensus recommendations.
• This process includes rounds of individual comments followed by round-table discussion at a face-to-face meeting, with anonymous voting as needed to determine the level of consensus.
• The level of consensus is specified:
  • Near-unanimous consensus, > 90% agreement
  • Uniform consensus, 76–90% agreement
  • Nonuniform consensus, 50–75% agreement
  • Major disagreement, < 50% agreement.
• At least 75% agreement is required to support a recommendation for an intervention. If this is not achieved, the intervention is not recommended due to a lack of consensus.

Final review and approval

• A final review document (usually a manuscript for publication in a peer-reviewed journal) is circulated to the PWG for review and approval.
• This incorporates the consensus recommendations agreed during discussions at the face-to-face meeting, together with the level of evidence and strength of recommendation according to the modified GRADE approach (explained in the next section).
• No major changes are incorporated during this final review stage.

(2023) Evaluating the strengths and limitations of the included RCTs

The following factors are considered in evaluating the strengths and limitations of included RCTs:

• Is the analgesic intervention clinically relevant to current peri-operative care?
• Are the differences in pain outcomes between the study groups clinically relevant based on minimal clinically important differences?
  • Clinically relevant differences in pain scores (≥ 10 mm/100 mmin pain scores).
  • Clinically relevant reduction in cumulative opioid use (e.g. reduced opioid-related adverse events).
• Does balance between the invasiveness of the analgesic intervention and the degree and consequences of postoperative pain allow recommendation?
  • For example, although epidural analgesia provides excellent pain relief, its use for minimally invasive surgical procedures may be inappropriate as it is invasive and provides a poor risk/benefit ratio, and similar postoperative outcomes can be achieved with combinations of non-opioid oral analgesics and local anaesthetic infiltration.
• Does the balance between efficacy and adverse effect profile of the analgesic technique allow recommendation?
  • For example, even if an analgesic technique provides excellent pain relief it may not be appropriate if it delays ambulation (e.g. femoral nerve blocks).
  • Determination of adverse effects of the analgesic intervention may not be procedure-specific; however, the risks should be adjusted for the procedure being evaluated. Case–control, cohort or observational studies can be used to determine adverse effects of analgesic interventions.
• Would the analgesic intervention further improve pain relief, reduce opioid use or improve other pain outcomes when added to a basic analgesic regimen? Alternatively, would the analgesic intervention be beneficial if a basic analgesic regimen were not administered or contraindicated? Also, would the analgesic intervention benefit challenging populations such as those at high risk of postoperative pain?
• Would the analgesic intervention potentially enhance recovery beyond the benefits on analgesia?
• (2023) Other possible considerations:
  • Overall quality of the trial (e.g. risk of bias scoring; sample size; pain at rest vs. procedure-relevant movement).
  • Although it is not appropriate to recommend an analgesic intervention based on one RCT, neither is a specific minimum number of trials (i.e. two or more RCTs) required for providing recommendations.
  • Although not taken in isolation, the country of origin could be used to understand the context of the clinical study, or to flag a need to confirm that the included studies do not come from the same institution. This information will not be included in the manuscript for publication unless there may be a potential question on interpretation of the available trials.
  • A caution is given if the recommendation is based upon several trials from the same institution(s).
  • The quality of the journal (e.g. low impact factor) in which the paper is published may be used to flag a need to check study quality.

• The previous approach to assigning the level of evidence and grade of recommendation for each PROSPECT recommendation is now replaced with the modified GRADE approach, which assigns a level of evidence and strength of recommendation (Guyatt 2011; Andrews 2013; Neumann 2016), as detailed below.
  • With the modification, the level of evidence is not assigned based on the estimate of the effect, as that may not always be possible to calculate given the heterogeneity of available evidence.
  • Also, the modification correlates with the level of consensus achieved during the modified Delphi process.
• The level of evidence is informed by the level of consensus achieved.
• The strength of recommendation would ideally match the level of evidence. Thus, a strong recommendation would be given rarely for very low level of evidence.
• The language used to reflect the level of evidence and strength of recommendations is suggested:
  • For recommendations with high or moderate levels of evidence, the term `recommend´ should be used
  • For recommendations with low or very low levels of evidence, the term `suggest´ should be used.
  • If no recommendation is made, it could be stated that `there is insufficient evidence concerning benefits and harms to recommend´.
• For interventions that are not recommended, the Strength of Recommendation and the Level of Evidence are not required. The reasons for not recommending analgesic interventions should be provided.

(2023) Modified GRADE approach to assign the level of evidence and strength of recommendations

Level of evidence

Strength of recommendation

• Despite the rigour of the PROSPECT methodology, there are some limitations, including:
  • The strength of the systematic review is based on the quality of published studies
  • Most RCTs assess a single-analgesic intervention with a placebo group commonly receiving opioid monotherapy and opioids as a rescue
  • Quantitative meta-analyses are generally not performed due to significant heterogeneity of the included RCTs
  • There is a lack of evidence on analgesic interventions for some specific surgical procedures, and a lack of accurate dosing and duration data
  • Some interventions, doses or routes of administration in published studies are no longer appropriate in current practice
  • Some analgesic techniques are introduced into current clinical practice without being subjected to a rigorous comparative study
  • Published literature may lag behind clinical practice, thus decreasing the clinical relevance of the review
  • Most studies of analgesic interventions do not assess their effects on clinically-relevant outcomes, such as movement-related pain scores or surgery-related physical function.
  • The PROSPECT working group does not include a patient representative for the Delphi approach.