SUMMARY OF 2020 BIOLOGIC ASSOCIATION SUMMIT
The 2020 Biologic Association Summit agenda included 1.5 days of lectures and didactic sessions provided by world renowned experts in all areas of orthobiologics. The opening session of the summit was entitled, “Biologics: What is Currently Available?” and provided cutting-edge lectures on PRP, bone marrow concentrate, adipose cellular therapy, amniotic cellular therapy, long- and short-acting cortisone injections, and viscosupplementation. The goal of this session was to provide a framework for the current state of biologic therapies in the United States and to disseminate knowledge on these critical therapies from leading experts.Rachel M. Frank,*† MD, Seth L. Sherman,‡ MD, Jorge Chahla,§ MD, PhD, Jason L. Dragoo,† MD, Bert Mandelbaum,‖ MD, and Members of the Biologic Association¶
Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or “stem cells”) is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment. Furthermore, biologic treatments may have potential devastating complications when proper methods or techniques are ignored. For these reasons, an association comprising several scientific societies, named the Biologic Association (BA), was created to foster coordinated efforts and speak with a unified voice, advocating for the responsible use of biologics in the musculoskeletal environment in clinical practice, spearheading the development of standards for treatment and outcomes assessment, and reporting on the safety and efficacy of biologic interventions. This article will introduce the BA and its purpose, provide a summary of the 2020 first annual Biologic Association Summit, and outline the future strategic plan for the BA.
Keywords: biologics; Biologic Association; osteoarthritis; platelet-rich plasma; stem cells; orthobiologics
*Address correspondence to Rachel M. Frank, MD, Sports Medicine and Shoulder Surgery, Department of Orthopaedic Surgery, University of Colorado School of Medicine, 12631 E. 17th Avenue, Mail Stop B202, Aurora, CO 80045, USA (email: rachel.frank@ucdenver.edu; website: www.RachelFrankMD.com).
†University of Colorado School of Medicine, Aurora, Colorado, USA.
‡Stanford University, Palo Alto, California, USA.
§Rush University Medical Center, Chicago, Illinois, USA.
‖Cedars-Sinai Kerlan-Jobe Institute, Santa Monica, California, USA.
¶All authors are listed in Authors section at the end of this article.
Final revision submitted March 2, 2021; accepted March 21, 2021. One or more of the authors has declared a potential conflict of interest or source of funding: see supplemental material for details. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
The Orthopaedic Journal of Sports Medicine, 9(6), 23259671211015667
DOI: 10.1177/23259671211015667
© The Author(s) 2021
Following a question-and-answer session, the next session focused on the important topic of “Regulatory Process and Ethical Implications” and included lectures on regulatory processes, implications of using products “off-label,” nomenclature challenges, complications associated with rogue stem cell clinics, and an overview of cellular expansion and culture. This critical session provided vital information on how to use and research biologics safely and to begin to reach consensus on the confusing nomenclature related to biologics. Even among experts, the definition of a “stromal cell” or “stem cell” is controversial. The content provided in this session helped develop consistent concepts and terminology and set the stage for establishing consensus with respect to current and future biologic technologies. While outside the scope of this review, future publications will discuss consensus statements generated with validated research methods.
The next session of the BA Summit expanded upon the framework provided by the first 2 sessions and discussed real-world clinical applications of biologics, including the use of biologics for tendinopathies, osteoarthritis and acute tendon injuries, either alone or as augmentation to surgical repairs and reconstructions, such as anterior cruciate ligament reconstruction and rotator cuff repair. From here, the afternoon continued with a session on the use of biologics in the office setting with respect to office management and logistics, and it provided the attendees with real-life context as to how practitioners are currently utilizing biologics on a daily basis. The final session of the first day of the Summit focused on the status of the BA as a means to transparently introduce the organization to the attendees and discuss its purpose and future strategies, mission, vision, and goals.
FUTURE GOALS AND HOW TO ACCOMPLISH THEM
Overall, the BA seeks to develop a musculoskeletal collaboration for shared and coordinated efforts to (1) establish a unified voice of recognized and expert musculoskeletal practitioners in the orthobiologics space to advocate for the safe and ethical use of orthobiologics in clinical practice; (2) lead efforts to develop standardized definitions, terminologies, and reporting requirements; (3) monitor and participate in the assessment and reporting of the safety and efficacy of orthobiologic interventions; and (4) advocate for patient education, awareness, and protection. Over the past 2 years, the BA has pursued this mission by developing a grassroots effort into an international, collaborative organization focused on providing the best possible care for patients and education for peers. Despite being a new organization, the cumulative experience of the leadership andmembership of the BA speaks to its ability to set and accomplish goals.| Subcommittee | Goal/Mission |
|---|---|
| Advocacy |
To facilitate a means to allow for development in the field of biologics across local,
regional, national, and international boundaries to best serve our patients and peers. To promote patient education and awareness as well as facilitate patient and practitioner reporting of false claims and adverse events. |
| Education and Best Practices |
To develop a forum for the anonymous reporting of rogue “stem cell clinics.” To produce best practices summaries and consensus statements, resulting in peer-reviewed publication and presentations. |
| Registry and Biorepository | To establish and maintain a biologics registry for outcomes and complications and develop a biospecimen and tissue repository for future research purposes. |
| Standards | To establish standards and ensure all material presented by the BA meets those designated standards in a transparent, unbiased, and ethical manner. |
| Finances and Membership |
To increase membership across all orthopaedic and musculoskeletal societies,
both operative and nonoperative. To ensure business matters of the BA are carried out in a responsible, ethical, and transparent fashion. |
| Website Oversight | To improve website accessibility, design, and content, while ensuring that only rigorous, peer-reviewed, evidence-based material is available via our site. |
| Scientific and Education Meetings |
To maintain a high-quality annual BA Summit to deliver the most up-to-date information
on current and future biologic interventions, plan future breakout meetings specific to biologic topics
including specific interventions (ie, cellular therapies), and plan future lab-/skills-based courses. To provide regular webinar/virtual educational content focused on the clinical application of orthobiologics to educate colleagues in real time. To provide regular webinar/virtual educational content focused on ongoing research related to orthobiologics to educate colleagues in real time on areas of current and future investigation. To provide support to the other subcommittees as well as society/individual members from a scientific and research perspective. |
The Advocacy Committee is critical in helping to maintain a unified voice to advocate for the safe, ethical, and efficacious use of orthobiologics in clinical practice and for patient education and awareness. By prioritizing safe and ethical patient care, this committee seeks to put patients first at all times, regardless of outside influences and agendas. Action items of this subcommittee include improving transparency and accuracy of physician, practice, and biologics-focused websites and advertisements. The advocacy committee also seeks to work with other organizations, including state advocacy programs and the US Food and Drug Administration, as well as social media platforms, to better educate colleagues, patients, and the public on important biologics topics.
The Education and Best Practices Subcommittee aims to produce consensus statements and critical analysis reviews based on the best available peer-reviewed literature to help guide clinical and surgical decision making regarding the use of biologic therapeutics. This group has developed several peer-reviewed scientific articles with additional manuscripts in development.5,6 Through this subcommittee, we hope to provide a unified voice to guide the ethical use of biologics and provide a rigorous, peer-reviewed library of clinical literature that has been vetted by experts. In addition, given the speed at which the biologics field is advancing, the subcommittee hopes to keep pace with the introduction of novel biologic technologies and techniques by providing a fast, up-to-date, and rigorous peer review, ensuring a safe and ethical platform for disseminating knowledge and innovation.
The Registry and Biorepository Subcommittee has perhaps one of the most important tasks within the BA: to establish a worldwide registry for the use of biologics. This registry will start small with the intention to be a reference tool for the collection of worldwide data with the goal of global expansion. This registry will go through the institutional review board approval process and will ultimately include deidentified information on patient demographics (age, sex, pathology, concomitant pathologies, prior treatments, activity level, etc), treatments (type, frequency, volume, location, indication, etc), validated patient-reported outcomes (PRO) measures, and complications/adverse events. The goal will be to have >75% follow-up across all clinical sites, and to include specific information on actual procedures (what is injected, how it is processed, the system used, etc) aswell as standardizedPROs. The clinical datawill be linked to a repository of biospecimens. Given the heterogeneity in different biologic formulations, there is a critical need to correlate the clinical and imaging outcomes with the composition and biologic activity of the particular treatment. We will develop a system to procure, process, and bank a sample of the specific biologic formulation in a biorepository for later measurement of the cellular, proteomic, and transcriptomic content and biologic activity. These measurements can be later correlated with the clinical and imaging outcomes to identify the specific factors related to successful treatment outcomes. This information will be combined with data on patient demographics, co-morbidities, radiographic studies, and PRO measures to gain a comprehensive understanding of the effect of biologic therapies inmusculoskeletal medicine.Another goal of this committee is todevelopa repository of surgical tissue specimens and joint fluid aspirates in order to better define the underlying pathology of various conditions, which will help to identify the biologic targets for treatment with biologic interventions.
The Standards Subcommittee will work in conjunction with the other subcommittees and will ensure that all scientific papers, data, statements, and reports generated from the BA meet a minimum standard of care. It will also seek to develop standardization in the definition of biologic therapies and outcomes metrics reporting, in an effort to define a minimum standard of reporting for peer-reviewed publication. Finally, this subcommittee will be responsible for creating standards for orthobiologic provider training and defining scope of practice.
The Finances and New Membership Committee will ensure a standardized and transparent process for vetting new potential members to the BA while ensuring that the organization can operate within an appropriate annual budget. As the BA intends to be inclusive, a specific set of organizational and operational guidelines will be maintained and updated by this subcommittee to ensure a fair and transparent process for appropriate membership expansion.
The Website Oversight Committee has created a robust website with peer-reviewed content and materials (https:// www.thebiologicassociation.com/). The ultimate goal of the website is to allow for the sharing of peer-reviewed data and dissemination of information on all topics related to biologics. Finally, the Scientific and Education Meetings Subcommittee has the responsibility of ensuring the delivery of relevant, accurate, efficacious, and ethical content to attendees during our educational conferences and proceedings, including the 2020 Biologic Association Summit.
RESEARCH AGENDA FOR THE BIOLOGIC ASSOCIATION
One of the most important priorities of the BA is to bring together clinician-scientists, basic scientists, and clinical researchers from centers within the BA membership that are conducting high-quality research focused on orthobiologics. At each annual BA Summit, we aim to highlight research findings from these research teams, allowing for discussion (and collaboration) on current and future research projects. In addition to the annual summit, we aim to hold regular meetings (in-person and/or virtual) with smaller groups to discuss research findings in real time, and provide opportunities for collaboration, including the potential for multi-institutional prospective studies. Over the next several years, some of our top research priorities include investigating the following factors as they relate to the research, development, and production of biologics:1. Determine the efficacy of biologics treatment.
2. Identify which patient-specific factors (ie, age, comorbidities, etc), as well as preparation-specific factors (ie, timing of treatment, delivery method, number of treatments, etc), are associated with response (or lack of response) to treatment.
3. Establish pragmatic and reliable standards on preparation of biologic therapies.
4. Identify factors that affect the composition and biologic activity of biologics (ie, details related to processing and preparation), and identify key components of biologics (ie, specific growth factors and/ or tissue-specific components) that may be amenable to biologics development.
5. Identify target tissues that would be most responsive to biologic therapy.
6. Identification of specific, validated outcomes measures and timing for clinical improvement.
7. Cost-effectiveness analyses of different biologic interventions, including office-based and operating room–based procedures.
SUMMARY
The BA has grown from merely a conceptual framework to an organization that has successfully implemented its mission to foster a collaborative group of thought leaders to present a unified voice in the musculoskeletal biologics environment, advocating for the responsible use of biologics in clinical practice, fostering patient awareness and education, spearheading standards development, and assessing and reporting on the safety and efficacy of biologic interventions. Pillars fundamental to the early success of this group include a focus on collaboration, inclusion, transparency, and integrity. The inaugural BA Summit, in collaboration with our founding members (ICRS, AOSSM, AANA, and ON Foundation), aims to set a standard to provide rigorous, evidence-based information for clinicians, scientists, and patients interested in biologics. We hope this will foster and encourage future collaborations and innovations in the field of musculoskeletal biologics.MEMBERS OF THE BIOLOGIC ASSOCIATION AT THE TIME OF THE 2020 BA ANNUAL SUMMIT
Adam W. Anz, MD; James P. Bradley, MD; Constance R. Chu, MD; Brian J. Cole, MD, MBA; Jack Farr, MD; David C. Flanigan, MD; Andreas H. Gomoll, MD; Joanne Halbrecht, MD; Kay Horsch, PhD; Christian Lattermann, MD; Philipp Leucht, MD; William J. Maloney, MD; Louis F. McIntyre, MD; Iain Murray, MD, PhD; George F. Muschler, MD; Norimasa Nakamura, MD; Nicolas S. Piuzzi, MD; Scott A. Rodeo, MD; Daniel B.F. Saris, MD, PhD; William O. Shaffer, MD; Shane A. Shapiro, MD; Kurt P. Spindler, MD; Matthias Steinwachs, Prof.Dr.Med.; John M. Tokish, MD; C. Thomas Vangsness, MD; John Tracy Watson, MD; Adam B. Yanke, MD, PhD; and Kenneth R. Zaslav, MD.REFERENCES
1. Chu CR, Rodeo S, Bhutani N, et al. Optimizing clinical use of biologics in orthopaedic surgery. J Am Acad Orthop Surg. 2019;27(2): e50-e63.2. Doral MN, Tandog˘ an RN, Mann G, Verdonk R. Sports Injuries: Prevention, Diagnosis, Treatment and Rehabilitation. Springer; 2011.3. Goodman SB, Yao Z, Keeney M, Yang F. The future of biologic coatings for orthopaedic implants. Biomaterials. 2013;34(13): 3174-3183.4. LaPrade RF, Geeslin AG, Murray IR, et al. Biologic Treatments for Sports Injuries II Think Tank—current concepts, future research, and barriers to advancement, part 1: biologics overview, ligament injury, tendinopathy. Am J Sports Med. 2016;44(12):3270-3283.5. Murray I, Chahla J, Frank R, et al. Rogue stem cell clinics. Bone Joint J. 2020;102(2):148-154.6. Piuzzi N, Rajan P, Kha S, et al. Classification and regulation of orthobiologics by the United States Food & Drug Administration. J Bone Joint Surg Reviews. 2020. Forthcoming.7. Toolan BC. Current concepts review: orthobiologics. Foot Ankle Int. 2006;27(7):561-566.The Orthopaedic Journal of Sports Medicine
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