Authors' objectives: To determine whether available evidence demonstrates IAHA provides clinically meaningful improvement in pain and function compared with placebo in patients with knee OA; to examine the potential harms of IAHA; and to assess whether net health outcomes are improved.

Authors' recommendations: A large body of evidence obtained from randomized controlled trials has examined the effect of IAHA on pain and function—a body of evidence subjected to many meta-analyses. If a clinically important treatment benefit different from placebo exists, accumulating evidence would be expected to increase certainty in that benefit and be sufficient to convince a decision-maker. Yet combined, the lack of defined meaningful clinical improvements over placebo, well-characterized biases among trials, publication bias, and uncertainty concerning reported harms all contribute to a conclusion that the body of evidence is insufficient to demonstrate IAHA improves the net health outcome in patients with knee OA. Identified internal study and publication biases imply that an unbiased effect estimate is lower than any overall pooled result. Pain and function scores were generally better with IAHA. However, the evidence is not consistent with those reported improvements—and most importantly unbiased estimates—achieving a difference over placebo that is clinically meaningful. Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether the use of intra-articular hyaluronic acid (IAHA) for knee osteoarthritis (OA) meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria. 1. The technology must have final approval from the appropriate governmental regulatory bodies. Seven different formulations of hyaluronic acid products are currently approved for marketing in the United States for intra-articular injection in the knee. All were approved as class III devices via the U.S. Food and Drug Administration's Premarket Application approval process. All 7 devices are indicated for the "treatment of pain in osteoarthritis (OA) of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy, and simple analgesics, e.g., acetaminophen." 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. Although a large body of evidence assembled from randomized controlled trials has been examined in multiple meta-analyses, the evidence is insufficient to permit conclusions whether IAHA for OA of the knee provides a clinically meaningful benefit compared with placebo. 3. The technology must improve the net health outcome. The evidence is not sufficient to determine whether reported improvements in pain and function—and most importantly unbiased estimates—achieve a difference over placebo that is clinically meaningful. 4. The technology must be as beneficial as any established alternatives. Absent demonstrated clinically meaningful improvement compared with placebo, there are no relevant comparisons with established alternatives to consider. 5. The improvement must be attainable outside the investigational settings. The evidence has not demonstrated IAHA for OA of the knee improves net health outcomes in the investigational setting. Therefore, it cannot be demonstrated that improvement is attainable outside the investigational setting. Based on the above, the use of intra-articular hyaluronic acid (IAHA) for knee osteoarthritis (OA) does not meet the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria.

Project Status: Completed

Year Published: 2014

URL for published report: http://www.bcbs.com/blueresources/tec/vols/29/29_6.pdf

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: BlueCross BlueShield Association (BCBS)