Gabapentinoids in Total Joint Arthroplasty

AAHKS (AAOS methodology) offers external review to Partner Societies prior to Endorsement Determination. Following the committee’s formulation of the Clinical Practice Guideline draft, it underwent a peer review by the board of directors from AAHKS, ASRA, and the Hip and Knee Societies. The AAOS Evidence-Based Quality and Value Committee reviewed the Clinical Practice Guideline draft for endorsement. Additionally, the publication of the systematic review and meta-analysis on opioids in primary hip and knee arthroplasties that supported the formulation of the Clinical Practice Guideline has undergone peer review for publication.

AAHKS (AAOS methodology) does not have a public comment process.

Family Medicine, Internal Medicine General, Neurological Surgery, Neurology, Orthopaedic Surgery, Surgery General, Neuropathology, Pathology

Resources used to develop the Randomized Quality Appraisal System: • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org. The following domains are evaluated to determine the study quality of randomized study designs. • Guyatt, G. H., Oxman, A. D., Sultan, S., et al. (2011). GRADE guidelines: 9. Rating up the quality of evidence. Journal of Clinical Epidemiology, 64(12), 1311–1316.

The process for determining strength of evidence also considers the following domains: 1. Consistency/heterogeneity of results between studies. Do the results vary widely between studies in terms of strength of effect and direction of effect? 2. Indirectness/generalizability a. Indirectness of patient population. Is the population of the studies applicable to general clinical practice? b. Indirectness of interventions. That is, are the interventions in the studies applied in the same way as they would be in general clinical settings, and are they available in all clinical settings? c. Indirectness of outcomes. Are all relevant outcomes and follow up times evaluated in the included studies? Or, does the evidence only consist of surrogate or intermediate outcomes? 3. Imprecision of results. Are effect estimates from the studies, or the pooled effect in a meta-analysis, highly imprecise, with very wide confidence intervals? For example, if confidence intervals include what might be considered a strong effect, even though the outcome is not statistically significant, the strength of evidence would be downgraded. 4. Tradeoff between benefits and harms. A moderate or strong recommendation can only be made if the benefits of implementing the recommendation clearly outweigh the harms. For example, if multiple high quality RCTs showed that a treatment improves patient reported outcomes, but also greatly increased the risk of serious adverse events, the strength of evidence would be downgraded to limited. The physician work group also applies GRADE’s Evidence to Decision (EtD) framework to determine the final strength of recommendation (appendix 1). The EtD form (appendix 1) is filled out as applicable by the work group member(s) assigned to the PICO question before the meeting, and is used to facilitate discussion about the following issues that may warrant a lower or higher recommendation grade: 1. Certainty of evidence 2. Is there uncertainty over how people value the main outcomes? 3. Are the desirable effects large? 4. Are the undesirable effects small? 5. Are the desirable effects large relative to the undesirable effects? 6. Are resources required to implement the recommendation small? 7. Are the incremental costs small relative to the net benefits? 8. Is the recommendation likely to be acceptable to key stakeholders? 9. Is the option feasible to implement? The EtD allows the workgroup to apply their clinical experience to determine the feasibility and appropriateness of CPG recommendations in real world health care settings. The EtD is a balance between the rigid evidence rules of the systematic review and the real-world clinical expertise of the work group, which allows for a richer perspective, and results in recommendations that are more appropriate. The EtD allows the workgroup to consider possible harms of implementation that may not be well studied in RCTs. It also provides a structured and transparent way to describe how they arrived at the final strength of recommendation and allows readers to be better able to determine how the recommendation applies to their own clinical setting. For example, if high quality studies show that a new imaging modality is good at diagnosing joint infection, but the technology is very expensive and is unlikely to be available at most community medical centers. After filling out the EtD form, the work group may decide that the recommendation should be downgraded from high to moderate because it is not feasible to implement in smaller hospitals due to cost. A reader from a small community hospital is now better able to decide if the recommendation can be implemented at his/her own institution. Conversely, a reader from a high-volume academic medical center that has the imaging technology may decide to apply the recommendation in his/her clinical practice. Furthermore, if low quality studies show that not performing a certain intervention, yields exponentially higher mortality in patients, the work group may decide that the recommendation should be upgraded from limited to moderate because of the potential to prevent loss of life.

Judging the quality of evidence is only a steppingstone towards arriving at the strength of a CPG recommendation. The strength of recommendation also takes into account the quality, quantity, and the trade-off between the benefits and harms of a treatment, the magnitude of a treatment’s effect, and whether data exists on critical outcomes. Strength of recommendation expresses the degree of confidence one can have in a recommendation. As such, the strength expresses how possible it is that a recommendation will be overturned by future evidence. It is very difficult for future evidence to overturn a recommendation that is based on many high quality randomized controlled trials that show a large effect. It is much more likely that future evidence will overturn recommendations derived from a few small retrospective comparative studies. Consequently, recommendations based on the former kind of evidence are given a “strong” strength of recommendation and recommendations based on the latter kind of evidence are given a “limited” strength. To develop the strength of a recommendation, AAOS staff first assigned a preliminary strength for each recommendation that took only the final quality and the quantity of evidence (see Table 1). The recommendations can be further downgraded or upgraded based on the GRADE and Evidence to Decision framework criteria described above.

AAHKS provides funding for Guideline Development.

All authors or contributors to the Clinical Practice Guideline have provided a disclosure statement in accordance with the publicly available AAOS Orthopaedic Disclosure Program. All authors and contributors attest none of the disclosures present are relevant to the Clinical Practice Guidelines

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