“Everyday activities, including eating and talking, are often difficult for people with temporomandibular disorders (TMD), and many of them suffer severe chronic pain due to this condition. Common social activities that most people take for granted, such as smiling, laughing, and kissing, can become unbearable. This dysfunction and pain, and its associated suffering, take a terrible toll on affected individuals, their families, and their friends. Individuals with TMDs often feel stigmatized and invalidated in their experiences by their family, friends, and, particularly, a health care community that frequently relies on “seeing” a condition in order to treat it. Misjudgments and a failure to understand the nature and depths of TMDs can have severe consequences—more pain and more suffering—for individuals, their families, and our society. People with TMDs, desperate for solutions, often seek out multiple clinicians, turning to dubious treatments in search of a cure, which can potentially lead to iatrogenic injury and costly, yet ineffective, treatments.”
TMDs are common disabling conditions and from 6% to 12% of the population is estimated to experience clinical symptoms. The treatments include many devices that have limited evidence of safety and effectiveness and little comparative data is available. Data on long-term outcomes is particularly limited, leading to use of trial-and-error approach in treating patients. As a result, some patients develop serious conditions including worsened chronic pain, facial paralysis, disfigurement, infection, metal sensitivity, device migration within the skull, device breakage, reduced jaw mobility, increased opioid use and dependence, increased suicidality, and other serious adverse events. In 1991, the estimated annual U.S. economic impact of TMD was $32 billion. The 2020 NASEM report on TMD states, “Studies assessing the direct and indirect costs specific to a TMD diagnosis are rare. Research into the direct and indirect costs of TMD is needed, especially in light of the changing policies around health care delivery.”
There is an urgent need to understand factors that lead to patients’ experiences of success or failure for all TMD treatments, especially those that are irreversible such as temporomandibular joint (TMJ) implants, and, to share these with health care professionals and regulators for informed decision-making.
TMJ Patient Led Roundtable
The TMJ Patient-Led RoundTable comprises key stakeholders as partners including patients, the FDA, NIDCR, the Agency for Health Care Research and Quality (AHRQ), the American Association of Oral and Maxillofacial Surgeons (AAOMS), TMJ implant manufacturers, clinicians, scientists, advocacy organizations, and other experts, all under the auspices of Medical Devices Epidemiology Network (MDEpiNet). More importantly, the RoundTable is a vehicle in which patients play critical roles throughout all related activities. Following its first meetings, the members of the RoundTable assessed the current availability of data and the ability of third parties to access, collect, and compile scientifically valid information related to selected aspects of TMD patient therapies.
The first TMJ Patient-led RoundTable was held on June 16, 2016, at the FDA headquarters in Silver Spring, Maryland. The meeting led to the formation of four working groups that were tasked with addressing specific areas of study and a Steering Committee to oversee the project as a whole. More specifically the four Working Groups focused on (1) TMJ Patients: Natural History and Assessment of Biomarkers Associated with Outcomes in TMJ Implant Patients, (2) Patient Reported Outcomes Evaluation, (3) Physician and Patient Education/Patient-Centered Treatment, and (4) Data Collection and Analysis.
The RoundTable reconvened on May 11, 2018, at the FDA Headquarters to update participants on the results of the working group projects, establish a roadmap to address highlighted gaps in knowledge regarding TMD, and to identify data collection needs for the development of high quality, real-world evidence (RWE). The RoundTable concluded that a strategically Coordinated Registry Network (CRN) is needed to collect and generate accessible data on TMD and its care that is sufficiently relevant and reliable. This is necessary to better understand the disparate treatment pathways and outcomes that patients experience.
Development of TMJ – CRN
To address these challenges in a multi-stakeholder environment, the Food and Drug Administration (FDA), TMJ Association and Medical Device Epidemiology Network (MDEpiNet) in collaboration with many private and public sector thought leaders launched TMJ Patient-led Round Table (as detailed in the TMJ Patient Roundtable Briefing Report). One of the areas of focus called for the development of the national infrastructure for evidence generation evidence and appraisal.
To strategically advance this goal, FDA partnered with HHS Office of Assistant Secretary for Planning and Evaluation (ASPE) Patient-Centered Outcomes Research Trust Fund (PCORTF). Specific objectives are to bridge the patient centered outcomes research and innovation through Community of Practice of Coordinated Registry Networks (CRNs) in 12 strategic clinical areas (as reported in the 2021 Annual ASPE Report), including TMDs. With the support of FDA/ASPE/PCORTF grant the development of TMJ Coordinated Registry Network (TMJ-CRN) was launched in 2019.
The TMJ-CRN aims to develop the foundation for a national infrastructure for capturing real-world evidence in the TMD clinical space. This will ultimately help inform the development of scientifically robust, comprehensive treatment guidelines to enhance outcomes of TMD treatments based upon knowledge of a patient’s overall phenotype, disease progression, and treatment trajectory, while also improving the lives of patients suffering from TMD.
The main objective of the TMJ-CRN is to develop a standardized data infrastructure for capturing patient-generated data, physician experience, and other healthcare ecosystem data necessary to better understand the disparate treatment pathways and outcomes that patients experience. In doing so, it aims to advance incorporation of real-world evidence into regulatory decision-making with the special emphasis on patient generated data. The evidence generated in the CRN will help inform the development of precision medicine algorithms that predict individual outcomes from TMJ therapies, and development of evidence-based protocols, guidelines, and best practices for inclusion in professional health care curricula.
The accomplishment of these goals will begin to fill in gaps in our knowledge of treatment outcomes and help establish scientifically based clinical treatment guidelines. In the future, this information will lead to new medical research that establishes precision treatments for the heterogeneous range of disorders we call TMDs.
The TMJ-CRN leverages the TMJ Patient-Led Roundtable partnerships consisting of a collaboration between the FDA/Center for Devices and Radiological Heath (CDRH), The TMJ Association, AHRQ, Device Manufacturers, FDA/Center for Drug Evaluation and Research (CDER), FDA/Office of Women’s Health (OWH), TMJ Patients, Weill Cornell Medicine, and the National Institute of Dental and Craniofacial Research (NIDCR). The TMJ Patient-Led Round Table is supported by a number of agencies including MDEpiNet, The TMJ Association, TMJ Patients, the FDA, NIDCR, FDA/OWH, American Association of Oral and Maxillofacial Surgeons, American Society of Temporomandibular Joint Surgeons, Zimmer Biomet, TMJ Concepts, clinicians, scientists, advocacy organizations, and other experts, all under the auspices of MDEpiNet. The Steering Committee includes members from each of the participating organizations listed above.
Identification of Core Minimum Dataset
The core minimum dataset for TMJ-CRN was developed using Delphi method. First, data elements for inclusion in the TMJ-CRN core minimum dataset for the Delphi process were identified through the extraction of existing data sources that identified conditions overlapping with TMD. Following the data element extraction, the informatics and clinical working groups organized the data elements according to their context within the clinical workflow.
Establishing the Technological Platform for the Support of the TMJ-CRN
For an established CRN to reliably collect an accurate dataset, a robust technological platform such as the High-performance Integrated Virtual Environment (HIVE), was leveraged. The identified core minimum data elements were defined in the context of technical implementation within HIVE web-application framework.
The developers established the permissioned blockchain for storing data to enhance data security scenarios. Every data operation in HIVE was verified for its authenticity by an immutable record in the blockchain along with a set of requisite access control permissions associated with the originator of the operation. The infrastructure development was completed and demonstrated in early January of 2021 to the TMJ-CRN showing the maintenance of all data transaction information in blockchain, flexible recording of patient consent, data cataloging, and consent validation through smart contracts.