Results
Overview
The uterine fibroids working group consisted of 29 expert members, including practicing physicians, reviewers and medical officers from the FDA, researchers, industry representatives, and one patient representative. The working group co-chairs reduced the initial list of more than 350 potential data elements to 200 data elements that were included in the Delphi process. Completion of the Delphi surveys and group consensus resulted in the selection of 97 data elements and are reported in the appendix. These data elements were identified as relevant to surgical devices used for the treatment of uterine fibroids. Patient demographic variables (age, race, etc.) were not included in the Delphi selection process as a standard, harmonized set of demographic variables was selected based on work already conducted by a multistakeholder project sponsored by the Pew Charitable Trusts.21 The final data elements may be entered by patients, by physicians, or through a hybrid approach based on available technology.
Medical, reproductive, and gynecologic history
For patient medical history, there was consensus on capturing the presence of relatively common medical conditions among reproductive aged women that might affect complication risk during or after a procedure. These conditions included hypertension, diabetes, thyroid disease, and a history of thrombosis. Gynecologic conditions that frequently coexist or produce similar symptoms to uterine fibroids and which could affect treatment decisions and/or the likelihood of symptom relief, such as endometriosis and adenomyosis, were also identified. Because abnormal uterine bleeding is the most frequent symptom associated with uterine fibroids, there was consensus on including data on menstrual regularity, heaviness of flow, and whether the abnormal bleeding had resulted in anemia, with or without a transfusion (as a marker of severity). Although there was consensus on the value of these data, the participants recognized that there is considerable variability in how this information is elicited from patients and recorded by clinicians, and that further work on reaching consensus on standards for reporting is needed. There was consensus on including data on previous pregnancy, including number of pregnancies, outcomes (miscarriage, abortion, live birth, stillbirth), gestational age, and delivery type. Pregnancy-related data elements were considered important for several reasons, including a potential association between fibroids and outcomes, the impact of mode of delivery on choice of treatment approach (such as scarring from previous cesarean sections), concordance with other WHT-CRN registries, and, importantly, the potential for using those same elements as outcomes for uterine-preserving treatments.
Data elements specific to fibroid history included current symptoms (bleeding, cyclic pain, non-cyclic pain, bulk symptoms, recurrent miscarriage), history and year of any prior procedures (abdominal, hysteroscopic, laparoscopic/robotic, or vaginal myomectomy, focused ultrasound, endometrial ablation, radiofrequency ablation, or uterine artery embolization), and current medical treatments (hormonal birth control, tranexamic acid, gonadotropin-releasing hormone (GnRH) agonists, or non-steroidal anti-inflammatory drugs).
Imaging data
There was consensus on including specific data elements from any imaging studies obtained prior to the procedure, including date, type of modality, and fibroid characteristics—location, size, number visualized, and number measured, as well as uterine dimensions if recorded. As with menstrual history, there was a recognition that there is considerable variability in how fibroid imaging is reported and recorded and that further work on developing standards was needed. There was also consensus that any radiologic suspicion of adenomyosis, endometriosis, or a potentially malignant uterine lesion should also be recorded.
Procedure data
The participants reached consensus on minimal data elements for all procedures, including whether the originally planned procedure was performed, procedure and discharge date, an identifier for the primary surgeon, occurrence of any intraoperative adverse events and an assessment about the relationship between the event and any devices used, other relevant intraoperative findings (eg, presence of adhesions), and other procedures performed (eg, oophorectomy). Relevant pathology findings, depending on the procedure, include uterine and ovarian pathology, uterine weight (for hysterectomy), number and cumulative weight of excised fibroids (for myomectomy), and use of morcellation (including device and containment status). For procedures that do not specifically remove tissues, such as uterine artery embolization, MRI-guided focused ultrasound, and radiofrequency ablation, stakeholders agreed to include details on the embolized arteries or the number of fibroids that were treated.
Post-procedure (short-term and long-term) data
At every follow-up interval, there was consensus on collecting data on post-procedure adverse events, whether cancer was diagnosed during follow-up, and treatment failure or recurrence of symptoms. Treatment failure and recurrence of symptoms was defined as the need for another fibroid procedure. If a cancer diagnosis was indicated, working group members agreed that it should be further specified if the cancer was leiomyosarcoma. There was also agreement that other measures of symptom recurrence, such as changes in a validated patient-reported outcome measure (PROM) or the need for new medical therapy, would be helpful. However, because of the lack of current standards for the use of PROMs in clinical practice, it was agreed that the chosen outcome measures were more reproducible and would capture the most important safety outcomes. As noted above, there was also recognition that pregnancy outcomes are important for many patients undergoing treatment for uterine fibroids, but that the data elements collected as part of the medical and gynecologic history would capture the most relevant outcomes at visits after the index procedure.
Informatics work
To create a CRN that is capable of conducting patient-centered outcomes research for multiple women’s health conditions (WHT-CRN), the FDA partnered with the Office of the National Coordinator for Health Information Technology (ONC), the National Library of Medicine (NLM), and a multistakeholder community coordinated by MDEpiNet in a large project funded by the Patient-Centered Outcomes Research Trust Fund (PCORTF) administered by the Office of the Assistant Secretary for Planning and Evaluation of the US Department of Health and Human Services.22 Through this project, core minimum data sets were concurrently being developed for stress urinary incontinence, pelvic organ prolapse, sterilization, and long-acting and reversible contraception. In order to create a CRN capable of evaluating medical devices used for all of these conditions, it was imperative to harmonize common data elements among all of the clinical areas to ensure interoperability of data sets stemming from future registries. After the core minimum data sets were developed for each of these clinical conditions, the project team formed an informatics team consisting of representatives from the National Institutes of Health (NIH), FDA, NLM, and ONC to lead the harmonization of each of the core data sets.
This group identified, compared, and aggregated data elements for each of the clinical areas prior to modeling. Any data elements that were common in at least two of the clinical areas were reviewed and refined through an iterative and collaborative process with both the informatics team and the clinical working groups, resulting in an initial set of harmonized common data elements. Modeling of data elements entails creating a form for each of the clinical registries in the NIH Common Data Elements (CDE) repository. Each form contained the full harmonized set of data elements with their associated permissible values linked to standardized codes and the data elements required in the Health Level Seven International (HL7) profiles. Code sets were included from standard clinical vocabularies, including the Value Set Authority Center,23 the Current Procedural Terminology, the Healthcare Common Procedure Coding System, and the International Classification of Diseases. The clinical working group reviewed these forms and provided feedback before the data elements were added to the HL7 Women’s Health Technologies (WHT) CRN Implementation Guide (IG).24
ONC will use the harmonized list of data elements in the WHT-CRN IG to define the data collection instruments and collect data for testing during pilot activities. The WHT-CRN IG is built to be an interoperable data exchange standard that consists of the resources, profiles, value sets, capability statements and specific implementation guidance for organizations (eg, hospitals, provider groups, researchers) to receive system data that meet current WHT-CRN use cases. Please see figure 1A,B for illustrations of how the WHT-CRN data will be collected and accessed by organizations. The WHT-CRN IG will also provide a platform for new use cases. The goal of this project is to make women’s health data available for exchange among providers and authorized researchers. Because this is also a goal of the Patient-Centered Outcome Research Network (PCORNet) and this project has been funded by the PCORTF, the WHT-CRN IG requirements have been drawn from the PCORNet use cases and implementations.25 Additional implementations that support this IG include the US-Core IG (mapped to the ONC 2015 Edition Common Clinical Data Set; Structured Data Capture Fast Health Interoperability Resources (FHIR) IG (the framework for questionnaire and questionnaire response resources); and the Patient-Reported Outcomes (PRO) FHIR IG (the framework for the Questionnaire Resource for capturing Patient Reported Outcome data). ONC will create new profiles and extensions for data elements that are not mapped to existing profiles. Registries will pilot the WHT-CRN FHIR IG in a test production environment (eg, clinical or provider setting), and/or manufacturing setting for CRN specific capabilities.26 Please see online supplemental file 2 for further clarification on these concepts and a full list of acronyms used in this manuscript.
Figure 1The abstract model, actors, and the data flow for WHT-CRN data collection. (A,B) Detail the capabilities required to implement a WHT-CRN workflow from the point of data collection to access of that data for research. The abstract model for collecting WHT-CRN data focuses on collection from patients undergoing various treatments of interest using a combination of clinical care delivery systems like EHRs and independent applications. The abstract model for accessing collected data from women’s health registries focuses on the ability of researchers to access the data currently collected and persisted in the registries. CRN, coordinated registry network; EHRs, electronic health records; IT, information technology; WHT, Women’s Health Technologies.
During the project, registry participants and CRN partners will continuously update the core common data elements within the IG and the sets of individual registry core data elements that are not represented in the IG. NLM will continue modifying the Pilot Harmonization form in the NIH CDE repository to supply the most recent vocabulary in the IG. NLM plans to update the CDE repository to support hosting, editing, harmonization, and export of the WHT-CRN data elements and other future CRN data elements. The data will be in machine readable format for use by data collection software applications for easier harmonization and reuse by stakeholders, specifically registries capturing device-related information on conditions affecting women. Technical assistance from NLM to support these efforts will include video tutorials and guides. In addition, throughout the pilot, the FDA and other stakeholders will continue monitoring and evaluating the implementation of the IG and the harmonized data set within clinical registries to support the refinement process. Patient data will be protected by institutional firewalls at each of the CRN’s clinical sites, and authorized researchers will only be able to access CRN data after going through a data sharing agreement process that will be managed by the MDEpiNet Coordinating Center.