Post-Wilk v. AMA: The Relationship Between Chiropractic and Organized Medicine

The relationship between the chiropractic profession and organized medicine in the United States since the landmark 1987 Wilk v.¹ AMA lawsuit has been defined by a gradual shift from professional antagonism to increasing interprofessional collaboration and integration into mainstream healthcare. The legal injunction in Wilk, which found the American Medical Association (AMA) guilty of an illegal restraint of trade against chiropractors, dismantled the formal boycott that had isolated the profession for decades. This legal resolution compelled changes in organized medicine's ethical guidelines. As early as 1980, during the litigation, the AMA revised its Principles of Medical Ethics to state that a physician "shall be free to choose whom to serve, with whom to associate, and the environment in which to provide medical services" ². By 1994, AMA Opinion 3.04 was updated to explicitly state that it was ethical for a physician to associate with and refer to "limited licensed practitioners," including chiropractors, provided the physician believed it would benefit the patient ³. As documented in historical accounts such as J. Stuart Moore's Chiropractic in America ⁴, these changes removed the formal ethical barriers to collaboration.

This new landscape facilitated the entry of chiropractic into large, federally managed healthcare systems, a process often driven by congressional mandates. The final report on the VA's Chiropractic Health Care Demonstration Program, for example, found high patient satisfaction and concluded that chiropractic care was a "useful addition" to VA healthcare offerings ⁵. This success supported further legislative action, such as Section 702 of the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001, which directed the Department of Defense (DoD) to implement a plan making chiropractic benefits available to all active-duty personnel ⁶⁷. Consequently, the integration of chiropractic services into the Department of Veterans Affairs (VA) grew significantly, with the number of VA facilities providing on-site chiropractic care increasing from 45 in 2010 to 101 by June 2019 ⁸.

This integration has been supported by a growing body of research and the inclusion of chiropractic therapies in major clinical practice guidelines. The influential 1992 RAND study on the cervical spine was an early example of a multidisciplinary effort to establish appropriate indications for manipulation ⁹. More recently, the American College of Physicians' 2017 guideline for chronic low back pain recommended spinal manipulation as an initial nonpharmacologic treatment option ¹⁰. In response to the opioid crisis, The Joint Commission's pain management standards, effective in 2018, now require accredited hospitals to provide nonpharmacologic pain treatment modalities, which can include chiropractic therapy ¹¹¹²¹³. This has created an institutional driver for integration, although barriers such as the need for medical staff sponsorship for hospital privileges remain ¹⁴. Within the VA and DoD, this integration often involves co-located clinics where chiropractors and medical physicians engage in frequent referrals and share electronic health records, a model of modern interprofessional care ¹⁵¹⁶. This article examines this evolution, tracing the pathways of integration from legal resolution to practical collaboration in contemporary healthcare settings.

The Wilk v. AMA aftermath and early research (late 1980s, mid-1990s)

The final injunction in the Wilk v. American Medical Association case in 1987 formally ended the AMA's organized boycott of chiropractic, compelling a fundamental shift in its ethical guidelines and opening the door to interprofessional relations. Even during the protracted litigation, the AMA had begun to alter its official position. In 1980, it revised its Principles of Medical Ethics, replacing the former Principle 3, which had been used to forbid association with chiropractors. The new version stated that a physician "shall be free to choose whom to serve, with whom to associate, and the environment in which to provide medical services" ². This change removed the explicit prohibition against associating with practitioners the AMA had deemed "unscientific" and represented an early crack in the wall of professional separation ⁴.¹⁷

Following the court's final ruling against the AMA, the organization made more direct and consequential changes. By 1994, the AMA's Council on Ethical and Judicial Affairs issued Opinion 3.04, which superseded a prior version (Opinion 3.01) ³. This new opinion explicitly clarified that it was ethical for a physician to associate with and refer patients to "limited licensed practitioners," a category understood to include doctors of chiropractic, provided the physician was confident that the referral would benefit the patient and contribute to their well-being ³. This policy officially dismantled the decades-long ethical barrier to interprofessional cooperation and referral, representing a pivotal moment in the relationship between organized medicine and chiropractic ⁴.

Concurrent with these legal and ethical shifts, the era saw the emergence of influential, multidisciplinary research that began to scientifically evaluate chiropractic procedures. The new professional climate, free from the threat of AMA sanction, facilitated collaborations between chiropractors and medical researchers that were previously untenable. A landmark example was the 1992 study on the appropriateness of manipulation and mobilization of the cervical spine, conducted by the RAND Corporation ⁹. This extensive project involved a systematic review of over 500 scientific articles to develop a comprehensive set of indications for using these procedures for conditions such as neck pain and headaches ⁹. A critical feature of the study's methodology was its use of a nine-member multidisciplinary panel, which included medical doctors, osteopathic physicians, and chiropractors, to rate the appropriateness of the indications. The RAND study was significant not just for its conclusions but for its process, which modeled a new form of evidence-based, interprofessional evaluation of chiropractic care. This period of the late 1980s and mid-1990s was thus defined by these dual developments. The legal resolution of the Wilk case provided the professional legitimacy and freedom of association, while rigorous scientific inquiry began to build an evidence base for specific chiropractic interventions.

Tentative steps toward integration and identified barriers (1990s)

The 1990s began with a new, albeit tentative, era of professional association between medicine and chiropractic, directly resulting from the Wilk v. AMA injunction. This shift was codified by the American Medical Association, which by 1994 had issued Opinion 3.04 of its Principles of Medical Ethics. This opinion stated it was ethical for a physician to associate with and refer patients to "limited licensed practitioners," including chiropractors, as long as the physician believed the referral was in the patient's best interest ³. This policy revision effectively dismantled the formal ethical boycott and created the first sanctioned pathway for interprofessional cooperation in a generation, as chronicled in historical accounts of the profession's struggle for legitimacy ⁴.¹⁸

This new environment enabled the creation of the first federally sponsored chiropractic demonstration programs, most notably within the Department of Veterans Affairs (VA). Mandated by Congress, the Chiropractic Health Care Demonstration Program ran from 1995 to 1997 at several VA medical centers to assess the feasibility of integrating chiropractic services. The program's final report yielded significant findings that would influence future policy. It documented very high patient satisfaction among veterans receiving chiropractic care, who rated their experience with a mean score of 8.4 on a 10-point scale ⁵. In addition to patient-reported outcomes, the report noted positive clinical improvements. Based on this evidence, the study's authors concluded that chiropractic care was a "useful addition" to the VA's existing healthcare offerings and recommended its inclusion as a benefit ⁵. This program served as a crucial proof-of-concept, showing that chiropractic services could be successfully delivered within a large, integrated federal health system with positive patient reception.

However, the success of isolated demonstration projects did not translate into widespread or easy integration, especially concerning chiropractors' access to hospital privileges. Significant institutional and professional barriers remained, which were later documented by research analyzing access issues during this period. A 2005 study by Hawk et al. published in the Journal of Manipulative and Physiological Therapeutics identified several key impediments that characterized the 1990s landscape. A primary obstacle was the common hospital bylaw requiring that an applicant for clinical privileges be sponsored by a current member of the medical staff, a difficult requirement for chiropractors who often lacked strong professional ties with medical physicians ¹⁴. Furthermore, most hospitals lacked specific institutional processes for credentialing doctors of chiropractic; their credentialing committees were unfamiliar with chiropractic education and licensure, creating an administrative impasse ¹⁴. Finally, chiropractors faced competition from other professions already established within hospitals, particularly physical therapy, which guarded its scope of practice related to manual and spinal therapies ¹⁴. These structural hurdles meant that while the legal and ethical gates had been opened, the practical pathways to full integration within hospitals remained largely blocked.

Legislative mandates for military integration (late 1990s, early 2000s)

While efforts to integrate chiropractic into civilian hospitals faced significant structural barriers, a parallel and more successful path was forged through federal legislation aimed at the U.S. military and veteran populations. The 1990s saw the establishment of several congressionally authorized demonstration projects designed to assess the feasibility and value of chiropractic care within federal health systems. A key example was the Veterans Health Administration's Chiropractic Health Care Demonstration Program, which ran from 1995 to 1997. The final report on this program documented high levels of patient satisfaction, with a mean score of 8.4 on a 10-point scale, and clinical improvements that led evaluators to conclude chiropractic care would be a "useful addition" to the VA's healthcare services ⁵. The positive outcomes of such pilot programs provided crucial data and political momentum for advocates seeking permanent and system-wide integration.

This momentum culminated in a landmark legislative directive that marked a definitive shift from voluntary pilots to mandated access. In 2000, Congress passed the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001. Section 702 of this act contained a provision that fundamentally altered the landscape for chiropractic within the armed forces ⁶. The legislation explicitly mandated that the Secretary of Defense develop and implement a comprehensive plan to establish chiropractic services as a permanent health benefit within the Defense Health Program, making it available to all active-duty members of the uniformed services ⁷. This was not a suggestion or a temporary trial; it was a direct order from Congress to the Department of Defense (DoD), effectively bypassing the professional and administrative resistance that had stymied integration elsewhere ⁴.

In response to the mandate, the DoD began a phased implementation, establishing chiropractic clinics at major Military Treatment Facilities (MTFs) across the United States and overseas. This process created government-sanctioned environments for interprofessional collaboration. Policy literature describes the emergence of co-located and integrated models of care within DoD and VA settings ¹⁶. In these clinics, chiropractors work in the same physical space as medical physicians, share common electronic health records, and participate in daily or weekly referral meetings and face-to-face consultations about patient care ¹⁵. This direct integration facilitated a level of professional interaction that was rare in the private sector. Subsequent research within the military health system demonstrated tangible benefits of this model; a 2018 study by Corcoran et al. published in JMPT found that military personnel who initiated care for low back pain with a chiropractor had lower odds of receiving an opioid prescription compared to those who started care with other providers ¹⁹. The legislative mandate, therefore, not only secured access for service members but also created a new paradigm for interprofessional practice and a valuable setting for health services research.

Systemic expansion in federal health systems (2000s, 2010s)

The integration of chiropractic into federal health systems accelerated significantly in the early 2000s, driven by direct legislative action. A key catalyst was Section 702 of the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001, which mandated that the Department of Defense (DoD) develop and implement a plan to make chiropractic services a permanent benefit for all active duty personnel ^{6 7}. This legislation marked a formal entry point into one of the nation's largest healthcare systems, moving beyond pilot programs to establish a durable presence.

Parallel to the developments in the DoD, the Department of Veterans Affairs (VA) was undergoing a similar, and in many ways more extensive, expansion. The foundation for this growth was laid by the VA's Chiropractic Health Care Demonstration Program. The final report on this program documented high patient satisfaction, with a mean score of 8.4 on a 10-point scale, and concluded that chiropractic care represented a "useful addition" to the VA's healthcare services ⁵. Bolstered by these findings, the VA system dramatically increased its chiropractic capacity. The number of VA facilities with on-site chiropractic clinics grew from 45 in 2010 to 101 by June 2019, a clear indicator of systemic adoption ⁸.

This expansion was not merely about adding services but about embedding them within new models of interprofessional collaboration ¹⁶. Within VA and DoD facilities, chiropractors often worked in co-located clinics, practicing in the same physical space as medical physicians. This proximity fostered a level of professional interaction characterized by daily or weekly referrals, frequent face-to-face case discussions, and the use of shared electronic health records ¹⁵. These integrated arrangements stood in stark contrast to the siloed, referral-only relationships common in private practice. The clinical focus also evolved; JMPT surveys from this period show that medical primary care providers in these settings were referring patients primarily for chronic, non-responsive musculoskeletal pain, a notable shift from the 1990s when referrals were more common for acute low back pain ²⁰. A 2019 survey of VA chiropractors confirmed this trend, finding most referrals came from primary care for conditions like low back pain without radiculopathy ²¹.

This federal integration was further encouraged by external clinical and regulatory forces. In 2017, the American College of Physicians released influential guidelines recommending that physicians and patients select nonpharmacologic treatments, including spinal manipulation, as the initial approach for chronic low back pain ¹⁰. Concurrently, the national opioid crisis prompted regulatory changes that favored non-drug therapies. The Joint Commission's revised pain management standards, effective January 1, 2018, required accredited hospitals to provide and educate on nonpharmacologic pain treatment modalities ^{11 13}. These standards, which explicitly aimed to reduce reliance on opioids, created a powerful institutional incentive for hospitals to formally integrate services like chiropractic therapy ¹².

Mainstream acceptance amid the opioid crisis (mid-2010s, present)

The institutional mandates from organizations like The Joint Commission created a clear pathway for chiropractic's inclusion in mainstream healthcare, particularly within large, integrated systems like the Department of Veterans Affairs (VA) and the Department of Defense (DoD) ^{12 13}. The groundwork for this integration was established earlier by legislation, such as the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001, which directed the DoD to make chiropractic services a permanent benefit for all active duty personnel ^{6 7}. The urgency of the opioid crisis accelerated the implementation and expansion of these services. Within the VA, the number of facilities with on-site chiropractic clinics more than doubled in a decade, growing from 45 in 2010 to 101 by June 2019 ⁸. This expansion facilitated new models of interprofessional collaboration, including co-located clinics where chiropractors and medical physicians practice in the same facility and share electronic health records ^{15 16}. In these settings, chiropractors often participate in daily or weekly referrals and engage in frequent face-to-face discussions with medical providers about patient care ¹⁵.

This integration altered referral patterns and demonstrated measurable outcomes related to opioid use. A 2019 survey of VA chiropractors found that most patient referrals came from primary care providers, with non-radicular low back pain being the most common diagnosis ²¹. This aligns with a broader trend observed since the 2000s, where medical referrals to chiropractors shifted toward patients with chronic, non-responsive musculoskeletal pain ²⁰. The direct impact on opioid prescribing was quantified in a 2018 study by Corcoran et al. published in JMPT. The study found that within the military health system, members who initiated care for low back pain with a chiropractor had lower odds of receiving an opioid prescription compared to those who started care with a primary care physician ¹⁹.

The American College of Physicians' (ACP) 2017 clinical practice guideline for low back pain provided a significant, if qualified, endorsement. The guideline recommended that for chronic low back pain, physicians and patients should first select nonpharmacologic treatments, including spinal manipulation, a core chiropractic therapy ¹⁰. While this recommendation strongly supported a non-drug-first approach, the ACP noted that the evidence supporting spinal manipulation for chronic low back pain was of "low-quality" ¹⁰. Despite this evidentiary caveat, the convergence of the opioid epidemic, influential clinical guidelines, and new hospital accreditation standards effectively repositioned chiropractic. It moved from a professionally segregated practice to an increasingly integrated component of institutional strategies for non-pharmacologic pain management.

Contemporary interprofessional practice and outcomes (late 2010s, present)

The institutional integration of chiropractic accelerated significantly in the late 2010s, particularly within large federal healthcare systems like the U.S. Department of Veterans Affairs (VA) and the Department of Defense (DoD). This growth was quantifiable; the number of VA facilities with on-site chiropractic clinics more than doubled in a decade, increasing from 45 in 2010 to 101 by June 2019 ⁸. This expansion provided a framework for new models of interprofessional collaboration that moved beyond historical animosity. Policy literature describes these arrangements as ranging from co-located clinics, where chiropractors and medical doctors practice in the same facility, to fully integrated models within patient-aligned care teams (PACTs) ¹⁶.

Within these integrated settings, day-to-day professional interaction became routine. Chiropractors participate in daily or weekly referrals, engage in frequent face-to-face discussions with medical physicians about patient cases, and share common electronic health records, which facilitates coordinated care ¹⁵. A 2019 survey of chiropractors practicing within the VA system confirmed that the primary referral pathway originates from internal medicine and primary care providers ²¹. The same survey found that the most frequently treated diagnosis was low back conditions without radiculopathy, establishing a clear clinical role for chiropractors within the system ²¹. This aligns with broader trends showing that medical primary care providers preferentially refer to chiropractors for chronic, non-responsive musculoskeletal pain ²⁰.

This period of increased integration coincided with a national public health crisis involving opioid over-prescription. In response, influential bodies began mandating non-pharmacologic approaches to pain. The Joint Commission's pain management standard PC.01.02.07, effective January 1, 2018, required accredited hospitals to provide and educate patients on non-pharmacologic pain treatment strategies ¹³. This policy directly supported the inclusion of services like chiropractic therapy to help reduce reliance on opioids ¹². Research conducted within these integrated systems began to demonstrate the value of this strategy. A 2018 study published in the Journal of Manipulative and Physiological Therapeutics by Corcoran et al. analyzed data from the military health system. It found that members who initiated care for low back pain with a chiropractor had significantly lower odds of receiving an opioid prescription compared to those who initiated care with a primary care physician ¹⁹. This evidence, demonstrating tangible public health benefits, further solidified chiropractic's role as a collaborative partner in mainstream healthcare settings.

Origins and early development

The formal end of organized medicine’s boycott against chiropractic, compelled by the 1987 final ruling in the Wilk v. American Medical Association (AMA) antitrust lawsuit, initiated a new and complex period of interaction. The court’s injunction forced the AMA to rescind its policies that had deemed it unethical for medical doctors to associate professionally with chiropractors. Even during the litigation, the AMA had begun to alter its stance under legal pressure. In 1980, it revised its Principles of Medical Ethics, replacing the restrictive Principle 3 with a new version stating a physician "shall be free to choose whom to serve, with whom to associate, and the environment in which to provide medical services" ². This process culminated after the injunction when, by 1994, the AMA’s official guidance in Opinion 3.04 explicitly stated that it was ethical for a physician to refer patients to or associate with "limited licensed practitioners," a category including chiropractors, so long as the physician believed the association or referral was in the patient's best interest ³. This change dismantled the primary formal barrier to interprofessional relations, shifting the dynamic from institutional hostility to one of cautious, individual professional judgment as described in J. Stuart Moore's history of the profession ⁴.

With legal barriers removed, the basis for interaction shifted toward scientific evidence and clinical efficacy. Mainstream medicine began to evaluate chiropractic methods, not through the lens of historical animosity, but through objective research. A landmark event in this transition was a 1992 study on the use of spinal manipulation for neck disorders, commissioned by the RAND Corporation. This extensive project involved a comprehensive review of more than 500 scientific articles and the formation of a multidisciplinary panel of experts, including both medical doctors and chiropractors, to rate the appropriateness of indications for cervical spine manipulation and mobilization for conditions like neck pain and headaches ⁹. The RAND study represented a significant moment of legitimization, as it subjected chiropractic procedures to the same type of rigorous, third-party scientific scrutiny applied to other medical interventions.

Despite these foundational changes, the path to integration was not immediate. The new ethical freedom to associate did not translate into widespread collaboration overnight. Decades of professional separation and skepticism had created significant cultural and practical hurdles. A 2005 study in the Journal of Manipulative and Physiological Therapeutics by Hawk et al. identified major systemic barriers that persisted in hospital settings well into the following decade. These included institutional policies that required medical staff sponsorship for chiropractors to obtain privileges, a lack of established processes for credentialing and privileging doctors of chiropractic, and professional competition from other established hospital services like physical therapy ¹⁴. This early post-Wilk period was thus characterized by the removal of official policy barriers, the beginnings of evidence-based evaluation, and the slow, challenging work of building new professional relationships on the ground.

Sources

1. Walter I. Wardwell, Chiropractic (1992) - https://openlibrary.org/works/OL4280776W

2. In 1980, during the Wilk litigation, the AMA revised its Principles of Medical Ethics, replacing Principle 3 to state a physician "shall be free to choose whom to serve, with whom to associate, and the environment in which to provide medical services." - https://law.justia.com/cases/federal/district-courts/FSupp/671/1465/1543323/

3. Following the Wilk injunction, the AMA's Principles of Medical Ethics were revised; by 1994, Opinion 3.04 (formerly 3.01) stated it was ethical for a physician to associate with and refer to "limited licensed practitioners," including chiropractors, provided the physician believes it benefits the pa - https://jamanetwork.com/journals/jama/article-abstract/417277

4. Chiropractic in America: The History of a Medical Alternative by J. Stuart Moore (1993) - https://books.google.com/books/about/Chiropractic_in_America.html?hl=&id=DSNtAAAAMAAJ

5. The final report on the VA's Chiropractic Health Care Demonstration Program found high patient satisfaction (mean of 8.4 on a 1-10 scale) and clinical improvements, concluding that chiropractic care was a "useful addition" to the VA's healthcare offerings. - https://www.va.gov/vhapublications/ViewPublication.asp?pub_ID=1092

6. Section 702 of the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001 directed the Department of Defense to develop and implement a plan to make a chiropractic benefit available to all active duty personnel. - https://www.gao.gov/products/gao-05-820

7. Section 702 of the Floyd D. Spence National Defense Authorization Act for Fiscal Year 2001 mandated the Secretary of Defense to develop a plan for providing chiropractic services as a permanent part of the Defense Health Program for all members of the uniformed services. - https://www.govinfo.gov/content/pkg/PLAW-106publ398/html/PLAW-106publ398.htm

8. The number of VA facilities with on-site chiropractic clinics increased from 45 in 2010 to 101 in June 2019, reflecting significant growth in the integration of chiropractic services. - https://www.jmptonline.org/article/S0161-4754(21)00028-7/fulltext

9. Coulter, I. D., Hurwitz, E. L., Adams, A. H., Meeker, W. C., Hansen, D. T., Mootz, R. D.,... & Shekelle, P. G. (1996). The Appropriateness of Manipulation and Mobilization of the Cervical Spine. RAND Corporation. - https://www.rand.org/pubs/monograph_reports/MR781.html

10. The American College of Physicians' 2017 guideline recommends for chronic low back pain, physicians and patients should initially select nonpharmacologic treatment including spinal manipulation (low-quality evidence). - https://www.acponline.org/acp-newsroom/american-college-of-physicians-issues-guideline-for-treating-nonradicular-low-back-pain

11. The Joint Commission's pain management standards, effective January 1, 2018, require accredited hospitals to provide nonpharmacologic pain treatment modalities, which can include chiropractic therapy. - https://www.jointcommission.org/-/media/tjc/documents/standards/r3-reports/r3_15_pain_assessment_and_management_hap_cah_17_2019.pdf

12. The Joint Commission's standards require hospitals to identify and treat pain, including providing non-pharmacologic strategies like chiropractic therapy, to help reduce reliance on opioids. - https://www.jointcommission.org/-/media/tjc/documents/resources/patient-safety-topics/quick-safety/qs_non-opioid-solutions-for-pain_8_15_18_final.pdf

13. The Joint Commission's pain management standard PC.01.02.07, effective Jan 1, 2018, requires accredited hospitals to provide and educate on non-pharmacologic pain treatment strategies, which facilitates chiropractic integration by mandating the availability of services like spinal manipulation. - https://www.jointcommission.org/-/media/tjc/documents/standards/r3-reports/r3_report_issue_11_pain_assessment_and_management_hap_cah_17_2019.pdf

14. The 2005 JMPT study by Hawk et al. identified major barriers to hospital access for chiropractors, including the requirement for medical staff sponsorship for privileges, lack of institutional processes for credentialing, and competition from other professions like physical therapy. - https://www.jmptonline.org/article/S0161-4754(05)00157-8/fulltext

15. Co-located chiropractors in military or VA settings participate in daily or weekly referrals, engage in frequent face-to-face discussions with medical physicians, and share electronic health records. - https://chiromt.biomedcentral.com/articles/1471-227X-20-1/figures/1

16. Policy literature describes several models of interprofessional collaboration in VA/DoD settings, including co-located clinics where chiropractors and medical doctors practice in the same facility, and fully integrated models within patient-aligned care teams (PACTs). - https://thespinejournalonline.com/article/S1529-9430(21)00216-7/fulltext

17. Joseph C. Keating, Chiropractic history: a primer (2004) - https://openlibrary.org/works/OL2025412W

18. Paul Smallie, Chiropractic History (1992) - https://openlibrary.org/works/OL4488688W

19. A 2018 study in JMPT by Corcoran et al. found that military health system members who initiated care for low back pain with a chiropractor had lower odds of receiving an opioid prescription compared to those who initiated care with a primary care physician. - https://www.jmptonline.org/article/S0161-4754(19)30113-7/fulltext

20. Post-2000 surveys in JMPT show medical primary care providers refer to chiropractors primarily for chronic, non-responsive musculoskeletal pain, a shift from the 1990s where referrals were more commonly for acute low back pain. - https://www.jmptonline.org/article/S0161-4754(09)00122-1/fulltext

21. A 2019 survey of VA chiropractors found that most patient referrals originated from primary care providers, with low back conditions without radiculopathy being the most frequently seen condition. - https://www.jmptonline.org/article/S0161-4754(21)00115-3/fulltext