Thyroid Health Outcomes Registry for Surgery

THORS is an umbrella real-world-data research program designed as an open, single-center, ambidirectional observational cohort. The historical component uses secondary data generated during routine care, including operative records, hospitalizations, pathology and immunohistochemistry reports, inpatient and outpatient clinical documentation, repeat admissions, follow-up encounters, and available resource/cost information. After registration, new eligible patients continue to enter the cohort prospectively as part of ordinary clinical practice, and clinically available follow-up information is added longitudinally. The research protocol does not assign the type or extent of thyroid surgery, lymph-node dissection, diagnostic testing, or adjuvant treatment.

The program uses linked patient-, hospitalization-, operation-, pathology-, complication-, and follow-up-level data structures. Raw source values, technically normalized data, automated screening signals, author clinical classification, independent expert classification, and adjudicated values are retained as separate layers whenever applicable. Each substantive substudy has a prespecified scientific question, eligibility criteria, outcome definitions, data freeze, and statistical analysis plan. Missingness, source provenance, discordance between data sources, classification error, and repeated observations within patients are explicitly evaluated.

Clinical objectives include description of surgical practice and pathology; clinically verified postoperative complications; functional outcomes; repeat, completion, and recurrence-related surgery; long-term oncologic outcomes; comparisons of clinically relevant surgical strategies when adequate confounding control is possible; and health-care resource use. Methodological objectives include reproducibility of cohort construction and phenotyping, multi-source detection and expert adjudication of outcomes, data-quality assessment, and the feasibility of measuring the 13 COS-DTC outcomes in routine data.

The historical cohort predates registration. Analyses already completed or initiated on historical data are treated as retrospective baseline analyses and are not represented as prospectively registered. Future substudies are date-stamped through protocol/SAP versions and frozen analytical datasets. The complete prespecified THORS research portfolio is listed in Appendix A of this registration dossier, including methodological, clinical, prognostic, comparative, economic, specialized, long-term, and transferability studies. Prospective questionnaires, research-only biospecimen collection, or additional study-specific procedures require the relevant ethics approval and, when they materially change the registered protocol, an amendment or a separate registration record.

Primary outcomes

• Clinically Verified 30-Day Postoperative Complication Rate [Within 30 days after each index thyroid operation]: Proportion of index thyroid operations followed by at least one clinically verified postoperative complication within 30 days, using prespecified event definitions, multiple routine-care sources where available, and expert adjudication. Complication types are reported separately and may include hypocalcemia/hypoparathyroidism, recurrent laryngeal nerve dysfunction, hematoma/bleeding, infection, chyle leak, unplanned reoperation, organ injury, readmission, and other clinically relevant events.
• Percentage of Participants With an Unplanned Reoperation Related to Thyroid Surgery Within 30 Days [Up to 30 days after the index thyroid operation]: The number of unique participants who undergo at least one unplanned surgical reoperation related to the index thyroid operation within 30 days will be divided by the number of participants with ascertainable 30-day follow-up and multiplied by 100. Planned completion thyroidectomy is classified separately and is not counted as an unplanned reoperation.

Secondary outcomes

• 30-Day Mortality [Within 30 days after index thyroid surgery]: All-cause death within 30 days of the index thyroid operation, using available in-hospital and post-discharge sources.
• Permanent Recurrent Laryngeal Nerve Palsy Due to Surgery [12 months after the index operation]: Persistent postoperative vocal-fold dysfunction attributable to surgery at 12 months, with preoperative dysfunction, tumor invasion, and intentional nerve resection considered separately.
• Permanent Postoperative Hypoparathyroidism [12 months after the index operation]: Persistent postoperative parathyroid dysfunction at 12 months based on prespecified biochemical and treatment criteria.
• Percentage of Index Operations in Each Final Histopathologic Diagnosis Category [Up to 90 days after the index thyroid operation]: Among index operations with a valid final pathology report, the number of operations assigned to each prespecified mutually exclusive diagnosis category will be divided by the total number of operations with valid final pathology and multiplied by 100. Categories are differentiated thyroid carcinoma, medullary thyroid carcinoma, other malignant thyroid neoplasm, benign thyroid neoplasm, non-neoplastic thyroid disease, and other or indeterminate pathology.
• Percentage of Participants With Persistent Differentiated Thyroid Carcinoma at 12 Months [12 months after the index thyroid operation]: Among participants with differentiated thyroid carcinoma and an ascertainable 12-month assessment, the number meeting the prespecified definition of structural or biochemical persistent disease at 12 months will be divided by the total number with an ascertainable assessment and multiplied by 100. A participant is counted once if either the structural or biochemical persistence criterion is met.
• Percentage of Index Operations in Each Mutually Exclusive Thyroid Resection Category [During the index thyroid operation]: The number of index operations assigned to each prespecified mutually exclusive thyroid resection category will be divided by the total number of eligible index operations and multiplied by 100. Categories are hemithyroidectomy, initial total thyroidectomy, completion thyroidectomy, and other thyroid resection.
• Median Available Direct Medical Cost of the Index Hospitalization [During the index hospitalization, from admission through discharge, up to 60 days]: Available direct medical cost for the index thyroid-surgery hospitalization will be summarized as the median with interquartile range in Russian rubles among hospitalizations with recorded cost data. Structurally unavailable cost values will be reported as missing and will not be automatically imputed.
• Percentage of Operations in Each Standardized Pathologic T Category [Up to 90 days after the index thyroid operation]: Among operations with morphologically confirmed primary thyroid carcinoma and an ascertainable pathologic T category, the number of operations in each standardized pT category will be divided by the total number of operations with an ascertainable pT category and multiplied by 100. The pT category is derived from the final pathology report using the prespecified staging rules.
• Percentage of Operations in Each Standardized Pathologic N Category [Up to 90 days after the index thyroid operation]: Among operations with morphologically confirmed primary thyroid carcinoma and an ascertainable pathologic N category, the number of operations in each standardized pN category will be divided by the total number of operations with an ascertainable pN category and multiplied by 100. The pN category is derived from the final pathology report using the prespecified staging rules.
• Percentage of Participants With a New Recurrence of Differentiated Thyroid Carcinoma [Up to 5 years after the index thyroid operation]: Among participants with differentiated thyroid carcinoma who have no evidence of persistent disease after initial treatment, the number who develop a new structural or biochemical recurrence will be divided by the number with evaluable follow-up and multiplied by 100. A participant is counted once if either the structural or biochemical recurrence criterion is met.
• Percentage of Index Operations With Central Neck Lymph Node Dissection [During the index thyroid operation]: The number of eligible index thyroid operations that include a central neck lymph node dissection will be divided by the total number of eligible index thyroid operations and multiplied by 100. Central and lateral neck dissections are classified separately according to the prespecified operation-classification rules.
• Percentage of Index Operations With Lateral Neck Lymph Node Dissection [During the index thyroid operation]: The number of eligible index thyroid operations that include a lateral neck lymph node dissection will be divided by the total number of eligible index thyroid operations and multiplied by 100. Central and lateral neck dissections are classified separately according to the prespecified operation-classification rules.
• Percentage of Participants Undergoing Planned Completion Thyroidectomy Within 12 Months [Up to 12 months after the initial hemithyroidectomy]: Among participants who undergo an initial hemithyroidectomy and are eligible for longitudinal trajectory assessment, the number who subsequently undergo a planned completion thyroidectomy within 12 months will be divided by the number with ascertainable 12-month surgical follow-up and multiplied by 100. Planned completion surgery is not classified as an unplanned reoperation.

Other outcomes

• Percentage of Required Real-World Data Elements With Available Values [At each annual data freeze, up to 5 years]: At each annual data freeze, the number of available values across the prespecified required data elements and eligible operation records will be divided by the total number of expected values for those elements and records and multiplied by 100. Missing, not assessed, not applicable, structurally unavailable, and contradictory values will remain distinguishable in the data-quality report.
• Percentage of Operation Records Requiring Manual Clinical Review [At each annual validation cycle, up to 5 years]: At each validation cycle, the number of eligible operation records referred for manual clinical review because of missing, conflicting, ambiguous, or rule-discordant information will be divided by the total number of eligible operation records evaluated in that cycle and multiplied by 100.
• Percentage of the 13 Core Outcome Set for Differentiated Thyroid Carcinoma Domains Classified as Analytically Resolvable [At each annual data freeze, up to 5 years]: At each annual data freeze, each of the 13 Core Outcome Set for Differentiated Thyroid Carcinoma domains will be classified using a prespecified binary readiness rule. A domain is analytically resolvable only when its definition, eligible population, assessment window, data source, and participant-level outcome status can be determined for the planned analysis. The number of resolvable domains will be divided by 13 and multiplied by 100.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patient undergoes or previously underwent an operation involving the thyroid gland at the study institution during the study period.
* The operation was performed for a benign or malignant thyroid disease, including primary, completion, or repeat thyroid surgery.
* Source data permit linkage of the patient, hospitalization, operation, and index date.
* For a specific substudy, the participant/episode meets the additional prespecified requirements for the relevant exposure and outcome.

Exclusion Criteria:

\- Procedure predominantly involving the parathyroid glands without a confirmed relationship to thyroid disease.

* Procedure or record without a confirmed relationship to thyroid disease.
* Technical duplicate record.
* Episode for which the essential temporal sequence or index date cannot be established for the relevant analysis.
* Record lacking the minimum data required to determine the primary outcome of the specific substudy.

• сергей Мосин, Principal investigator, Pirogov University (RNRMU)