The orthopaedic and sports medicine literature has embraced comparative effective research (CER), which focuses on evidence-based research to improve patient health. This chapter explores the various ways in which CER has been used and reviews its history and arrival as it relates to orthopaedic surgery and sports medicine.

CER was first established on June 30, 2009 with the introduction of the American Recovery and Reinvestment Act of 2009.¹,² This stimulus bill, alongside the passing of the 2010 Patient Protection and Affordable Care Act, enacted a shift in American health care, focusing on evidence-based research to improve patient health. CER represents the synthesis of available evidence and commitment to the generation of new research that identifies the value of interventions through the lens of outcomes and cost. This evidence is then used to guide decision-making in the most effective methods of prevention, diagnosis, and treatment of specific ailments, injuries, and diseases. Thus, CER was established to improve value in the United States across all major fields of medicine.²,³ With a budget of $1.1 billion, Congress allocated $400 million to the National Institutes of Health, $300 million the Agency for Healthcare Research and Quality and $400 million the Department of Health
and Human Services to promote and support the implementation of CER projects in the United States. To begin this endeavor, the Institute of Medicine and Congress recommended specific priorities to create and sustain a robust CER strategy moving forward. These priorities were aimed at addressing health care delivery systems and disparities, as well as cardiovascular disease, psychiatric conditions, neurologic disorders, and individuals with functional limitations and disabilities.⁴

To promote the continued support of CER, the Patient-Centered Outcomes Research Institute was enacted under the Affordable Care Act in 2010. This federally funded, nonprofit organization aimed to support the ideals of CER and guide governing bodies in making informed decisions regarding health care issues and health policy.³,⁵ Prompted by the mission of executing national health care research, Patient-Centered Outcomes Research Institute board members and stakeholders identified the following priorities to categorize their funding agenda: personcentered outcomes, health disparities, health care systems, communication and dissemination, and methodologic research.⁶ Since its inception, a total of $3.6 billion was allocated for CER-related activities during the 2010 to 2019 fiscal years. Under this funding agenda, 1,987 research awards, 379 research infrastructure awards, 103 engagement awards, and 60 dissemination and implementation awards have been granted for both ongoing and completed projects.⁷

It is common knowledge that experimental clinical research, namely the randomized controlled trial (RCT), is the gold standard for assessing the value of an alternative medical intervention. The increased validity and low bias associated with RCTs provide high causal evidence to the value of an intervention.⁸ However, the RCI has become increasingly impractical at both the patient and population level.⁸ The emergence of CER has prompted renewed interest within observational research methods in assessing the value of various medical interventions. Anglemeyer et al⁹ reported that health outcomes (risk, odds and hazard ratios) using observational methods were comparable to those from RCTs. As such, the value of clinical registries and electronic medical records has skyrocketed because of their capacity to store large volumes of data capable of fueling observational study designs.¹⁰,¹¹,¹²

Similar to the hospital electronic medical record, clinical registries contain important data for longitudinal research capable of comparing various orthopaedic interventions. Lake et al¹³ described the role of CER in spine surgery, specifically highlighting the need to determine the optimal treatment paradigm for common degenerative spinal disorders through the Swedish Spine Registry and the Registry of the Scoliosis Research Society.¹³ Spine surgery professional organizations are not the only orthopaedic subspecialty taking a recent interest in procedural-based and diagnosis-based registries. For example, the Hospital for Special Surgery conducts a number of registries to collect and analyze patientreported health outcomes, including their total joint replacement registry.¹⁴ Funded through grant support by the Agency for Healthcare Research and Quality, more than 10,000 patients have been enrolled in this registry since 2007.¹⁵ The Cleveland
Clinic Health System developed a scientifically valid, cost-effective, and scalable prospective registry, called the Outcomes Management and Evaluation system, that collects demographic data, general health patient-reported outcome measures (PROMs), joint-specific PROMs, and disease severity at the time of surgery for all elective hip, knee, and shoulder procedures across seven different hospitals within the system.¹⁶ Of the eligible 15,610 patients, 97.4% of patients completed PROMs and 99.9% of surgeons provided the necessary patient details of disease severity; at 1 year, the patient follow-up rate was 72.5%.¹⁶ Currently, more than 50,000 patients are prospectively enrolled in this registry. Other institutional registries have been established around the world to best explore outcomes for various interventions, including St. Vincent’s Melbourne Arthroplasty Outcomes Registry. To date, this registry reports more than 13,000 arthroplasties in more than 10,000 patients, with follow-up extending to 20 years after surgical intervention.¹⁷ From this registry alone, more than 46 observational studies have been published using this registry’s data.¹⁷ Though registry data are imperfect and less exact than the RCT, high-quality data with appropriate statistical analysis can yield similarly meaningful discoveries.¹⁸ Therefore, both the electronic medical record and clinical registry remain critical in CER for orthopaedics and sports medicine.

In order to compare surgical effectiveness in elective orthopaedic surgery, the advent of PROMs embodies the recent shift to patient-centered care and provides the quantitative springboard to allow comparison. PROMs have come to represent the greatest commitment to CER in orthopaedic research through the administration of survey instruments that capture patient perspectives and experiences following a procedure. Often encompassing subjective measures of symptoms, functional status, health perception, health-related quality of life, and satisfaction,¹⁹ Table 1 details various PROMs used among sports medicine surgeons: anterior cruciate ligament (ACL) reconstruction,²⁰,²¹ hip arthroscopy,²²,²³,²⁴ and rotator cuff repair and shoulder stabilization.²⁵ Nwachukwu et al²⁶ systematically reviewed 12 cost effectiveness analyses in the sports medicine literature and found the available evidence is limited to select procedures, primarily ACL reconstruction and rotator cuff repair.

Similar to clinical trials, PROMs can be statistically analyzed to determine the effectiveness of a given orthopaedic procedure. Beyond the characteristics of the musculoskeletal disease, PROMs can capture overall health status, including physical, mental, and emotional health. The most common global health measure administered in orthopaedics is the Short Form-36, which contains the Physical Component Summary Score and a Mental Component Summary Score to measure health-related QOL.²⁷ The advent of PROMs serves to elucidate the previously nebulous relationship between mental and physical health to identify ideal surgical candidates and provide reasonable prognoses for at-risk populations. As an example, Ramkumar et al²⁸ applied machine learning to PROMs collected in an institutional cartilage registry to establish that patients who preoperatively report poor mental health, catastrophize pain symptoms, compensate with higher

physical health and knee function, and exhibit lower activity demands are at risk for failing to reach clinically meaningful outcomes after osteochondral allograft of the knee.