David S. Jevsevar, MD, MBA
The AAOS, with input from representatives of the American College of Rheumatology, the American Academy of Family Practice, and the American Physical Therapy Association, recently published a collaborative clinical practice guideline (CPG) on the Treatment of Osteoarthritis (OA) of the Knee (Non-Arthroplasty)—2nd Edition. This evidence-based guideline contains 15 recommendations (Table 1 and Table 2), replaces the 2008 AAOS CPG, and was reevaluated earlier than the 5-year recommendation of the National Guidelines Clearinghouse due to methodologic concerns regarding the evidence used in the first CPG.
The accelerated update was authorized by the AAOS Board of Directors based on the following concerns. Specifically, the AAOS, in the first guideline, included evidence analysis from the following three sources:
- Agency for Healthcare Research and Quality evidence report, “Treatment of Primary and Secondary Osteoarthritis of the Knee”
- Osteoarthritis Research Society International guidelines
- Cochrane Database of Systematic Reviews (through February 22, 2008)
As was noted by several AAOS members and industry representatives, this differed from the AAOS standard of performing an independent analysis of the available evidence. The AAOS no longer relies on previous systematic reviews in its evidence analysis due to the significant variability in the included studies, the additional potential for bias, and the variable clinical applicability of those reviews, as highlighted in systematic reviews of joint replacement conducted by Mohit Bhandari, MD, McS, PhD, and colleagues.
This second edition of the CPG used the same questions asked in the 2008 CPG to guide its selection of medical subject heading terms used for the literature review. However, significant changes were made in the search inclusion criteria.
For example, all included studies had to have a sample size of at least 30 participants to limit the “small-study” effect of lower-powered clinical trials and to mitigate against publication bias in the evidence review. Additionally, all included studies had to have a follow-up period of at least 4 weeks. Thus, studies showing potential efficacy at 2 weeks after the intervention were not included in the update.
More than 10,000 separate pieces of literature were reviewed during the evidence analysis phase. The AAOS used a “best-evidence synthesis” form of evidence analysis, meaning that only higher quality evidence is used in meta-analysis and network meta-analysis.
When completed, the updated OA knee CPG was subjected to the most extensive peer review yet for an AAOS CPG. Sixteen peer-reviewers, representing multiple specialty societies, submitted formal peer reviews. Each meticulously dissected the final recommendations of the document and, based on their well-informed and insightful comments, important changes were made to the final document.
Reviewers correctly noted, for example, that the recommendations did not include “harm/risk” analysis, but rather only evidence of the presence or absence of effect. However, the original wording of “recommended against” could be interpreted as implying “harm” or “risk.” The workgroup agreed and changed the language of four recommendations (3A, 6, 9, and 12) to “we cannot recommend.” In addition, the wording for recommendations 5 and 11 was changed to “we cannot suggest,” which implies evidence only of a lack of efficacy.
Viscosupplementation recommendation changed
The 2013 OA knee treatment CPG contains one significant recommendation change from the 2008 CPG, and this is with regard to the issue of viscosupplementation. The 2008 OA knee CPG included an “inconclusive” recommendation regarding the use of intra-articular hyaluronic acid (HA) injections that was largely the motivating factor for the expedited update of the CPG.
The second edition CPG recommendation reads “We cannot recommend using hyaluronic acid (HA) for patients with symptomatic OA of the knee,” with a “Strong” rating, based on supporting evidence from 3 high-quality and 11 moderate-quality research studies that met the inclusion criteria.
The work group understands the potential impact that this recommendation could have on clinical practice. Nonetheless, the CPG’s best evidence synthesis does not support the efficacy of viscosupplementation. Although statistically significant outcomes were seen in some studies with higher molecular weight HA preparations, these outcomes were not clinically significant, based on a lack of minimum clinically important improvement (MCII). (For more information on MCII, see “The Importance of Clinical Significance in AAOS CPGs,” AAOS Now, May 2013.)
Although some reviewers have questioned the use of this metric in determining clinically significant differences in treatment outcomes, the AAOS believes this is the best way to measure such differences. Several systematic reviews on viscosupplementation have pointed out that the literature suffers from a significant degree of publication bias, noting that studies with results that did not support the use of viscosupplementation were less likely to be published than studies with positive results.
Despite this clear publication bias toward positive results, current published studies do not show a clinically effective response for HA injections based on MCII. Some peer reviewers were critical of this finding, especially in light of the important clinical practice implications. Many highlighted prior systematic reviews supporting the use of HA. These reviews were analyzed and found to have several flaws. Most did not address the issues of publication bias, between-study heterogeneity, and clinical significance in determining final recommendations.
Several reviewers noted that using the MCII to determine clinical significance has inherent faults. The AAOS CPG process has used MCII to elucidate clinical significance since its inception. This represents the best validated measure of minimum clinically important improvement when trying to determine whether a treatment truly has efficacy rather than just slight improvements that register as statistically significant.
Two other effect-size tools, the Patient-Acceptable Symptomatic State—an absolute score beyond which patients are satisfied—and the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials score, which denotes a specific percentage of patients who are satisfied, have methodologic limitations that make them less appropriate for the AAOS CPG analysis process.
The CPG workgroup accepted and fulfilled its obligation of academic rigor and ethics, which are assumed of all clinical research, without compromise or modification, despite significant criticisms from reviewers and commenters. Additional studies with high methodologic quality on the effects of high molecular weight preparations on OA knee with subgroup analysis are needed.
Changes in the strength of recommendations were based on their supporting evidence. For example, the recommendation on the use of intra-articular corticosteroid injections went from “We suggest …” to “We are unable to recommend for or against the use of …” Although some reviewers expressed concern about this change to a lower rating, intra-articular corticosteroid injections remain supported in clinical practice.
The recommendation on arthroscopic meniscectomy increased in strength from a consensus to an inconclusive recommendation, which is now supported by evidence and is no longer based solely on expert opinion. The current inconclusive recommendation does help the AAOS to support this procedure on patients with OA knee.
The second edition of the OA knee CPG addressed the concerns raised regarding methodologic flaws associated with the evidence base of the first edition. The AAOS CPG process benefitted and will continue to do so from the extensive involvement of the peer-reviewers and specialty societies. The process improves with the thoughtful criticism of the guidelines and the evidence synthesis process.
It is important to clearly state that this CPG, as with all AAOS CPGs, is not intended as a tool for coverage determinations. Misinterpretation of the goals and position of the CPG process can result in confusion of the message to patients, clinicians, and payers with resultant deleterious effects. The CPG process needs to be disseminated with the goals and limitations of the analysis clearly delineated and explained. This will mitigate against the potential misuse of the guidelines. The AAOS also remains committed to ensuring that the guidelines are interpreted and used properly and will advocate vigorously on behalf of patients and members.
The AAOS also plans to follow this CPG with an Appropriate Use Criteria (AUC). Although the CPG delineates whether a procedure, intervention, or diagnostic test “works,” the AUC will further define “in which patients” and “when” an intervention, procedure, or diagnostic test is appropriate. Work on the accompanying AUC for OA knee is currently underway.
The work group highlighted the need for better research in the treatment of OA knee, in addition to improved methodologies that differentiate responders from nonresponders. Evidence, whether strong or inconclusive, is never sufficient to make important clinical decisions. Individual values and preferences must balance the evidence to achieve optimal shared decision making and highlight that the practice of evidence-based medicine is not a “one-size-fits-all” approach. Evidence-based practice incorporates three components: scientific evidence, the clinician’s experience, and the patient’s values. No single component of patient care can stand alone.
The CPG on the Treatment of Osteoarthritis of the Knee (Non-Arthroplasty)—2nd Edition—including the full guideline document, along with all supporting documentation and workgroup disclosures—is available on the AAOS website, at www.aaos.org/guidelines
David S. Jevsevar, MD, MBA, chaired the volunteer workgroup that developed the CPG on the Treatment of Osteoarthritis of the Knee (Non-Arthroplasty)—2nd Edition.
Disclosure information: Dr. Jevsevar—Medacta USA; Omni Life Sciences.
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The Clinical Practice Guideline for the Treatment of Osteoarthritis of the Knee (Non-arthroplasty)—2nd Edition was developed by a volunteer work group chaired by David S. Jevsevar, MD, MBA, and Gregory Alexander Brown, MD, PhD. Members of this work group include the following: Dina L. Jones, PhD, PT; Paul A. Manner, MD, FRCSC; Elizabeth G. Matzkin, MD; Pekka A. Mooar, MD; John T. Schousboe, MD, PhD; and Steven Stovitz, MD. James O. Sanders, MD, served as the attending guidelines oversight chair; Michael J. Goldberg, MD, serves as chair of the Guidelines Oversight Committee and Kevin J. Bozic, MD, MBA, is chair of the Council on Research and Quality. AAOS staff included Patrick Donnelly, MA, lead research analyst; Deborah S. Cummins, PhD, director of research, and William R. Martin III, MD, medical director.
Funding was provided by the AAOS. The guideline is based on a systematic review of the current scientific and clinical research. The methods used to prepare the guideline were rigorous, employed to minimize bias and to develop a set of reliable, transparent, and accurate clinical recommendations for the prevention of orthopaedic implant infections in patients undergoing dental procedures. These methods are detailed in the full guideline.
The development of AAOS Evidence-Based Clinical Practice Guidelines are overseen by the Committee on Evidence-Based Quality and Value. The Clinical Practice Guideline for the Treatment of Osteoarthritis of the Knee (Non-Arthroplasty)—2nd Edition was approved by the AAOS Board of Directors on May 18, 2013. The complete guideline is available at www.aaos.org/guidelines
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