Prior cost-effectiveness analyses of treatment strategies for PHPT have found that surgery is preferable to observation or pharmacological therapy.4,42–45
Reported cure rates range from 95 to 98 % for both MIP and BNE approaches.3,7,10,12
Cost-utility analyses comparing MIP to BNE largely support the value of MIP; this was supported by our work.18–20,22
In keeping with the reported success of MIP, the majority of parathyroidectomies now performed in the United States are minimally invasive.5
Preoperative localization is required for MIP, traditionally with US and SM. Recent reports indicate 4D-CT to have improved sensitivity over US and SM; however, it is unclear if this modality should supplant or support standard imaging with ultrasound and sestamibi.13,14,16,17,39
Moreover, comparative costs of various screening strategies, vital in a potentially resource-constrained environment, are relevant.
In this analysis, we found that US followed by 4D-CT was the least costly strategy followed by US alone. In our study, differences in cost were largely based on improved sensitivity for detecting single gland disease and, therefore, on the proportion of patients able to undergo MIP with shorter operative time and same-day discharge. US followed by 4D-CT remained the best strategy over realistic ranges of SM, US, and 4D-CT costs and test performance for detecting single-gland disease. The percentage of patients admitted to the hospital following surgery has a large influence on cost. This decision will likely be primarily influenced by undergoing MIP versus BNE and surgeon preference. As anesthesia cost is time-based, small changes in OR times had a significant influence on cost. For instance, a 15 min interval of anesthesia cost ($126) is more than the cost of an US ($96).
To date, there is only one published study, by Wang and colleagues, comparing currently utilized screening strategies, including 4D-CT.46
In comparing our studies, there are a number of key differences in model parameters, strategies, and study design that warrant mention. In their study, all patients with MIP were assumed to have outpa-tient procedures, and all BNE were assumed to stay overnight. It is recognized, however, that the distinction between inpatient and outpatient surgery also is informed by practitioner preferences.5
As a result, we incorporated the proportion of cases likely to be managed as inpatient versus outpatient surgeries based on reported clinical practice patterns.5
Ultrasound alone was reported as the least costly strategy by Wang and colleagues; however, the strategy of US followed by 4D-CT, our preferred strategy, was not assessed in their study. Moreover, the authors chose to perform a cost-utility analysis using a disutility reported for patients undergoing bilateral versus unilateral surgery (utility difference of 0.006).42
Given that more research is still needed to better define utility differences between MIP versus BNE, or between localization strategies, we chose to limit our study to a cost analysis. In keeping with their study, we found strategies that integrated SM, alone or with other modalities, were more costly, and that direct BNE was the most costly.
On a clinical practice level, initial assessment with US is practical as increasing numbers of endocrine surgeons perform intraoffice ultrasound. Additionally, US allows for assessment of concurrent thyroid disease prior to surgery. Furthermore, the use of 4D-CT only in cases where US fails minimizes radiation compared to utilizing 4D-CT or SM as the first-line examination.
Our study has expected limitations, common to decision-analytic methods, which arise when using simplifying assumptions to model complex disease processes and care pathways. First, we did not include non-health care (e.g., time off from work) related costs to the patient in our analysis. Differential time off from work—in particular due to postoperative recovery from MIP versus BNE—may be possible. Incorporating time off from work, including a potential increased recovery time for BNE, would likely increase the magnitude of our results as this would make strategies with a higher proportion of patients undergoing BNE more costly. Second, to our knowledge, there are no reported data to inform the sensitivity of 4D-CT after negative US and assumed these tests to be conditionally independent in our base-case analysis. We addressed this limitation using sensitivity analysis—we found that US followed by 4D-CT remained the preferred strategy when sensitivity of 4D-CT after negative US was >39 %. Probabilities of single-gland disease prevalence and accurate parathyroid localization were extracted from the literature. Many of these estimates are based on retrospective data, and therefore, limited by selection bias and errors in collecting the data (i.e., misclassification). Furthermore, the survey data used for clinical practice patterns are limited by the sampling of survey responders, which may impact the generalizability of the results, as well as how accurately the responders answered (i.e., respondent and recall biases). To address these limitations, we performed a number sensitivity analyses to assess the stability of our results to varying model inputs.
In summary, we found that US followed by 4D-CT (if US indeterminate) was the least costly preoperative localization strategy for patients with PHPT. This finding was robust across a wide range of inputs. Differences in cost were influenced primarily by differences in the sensitivity of each strategy, which determined the proportion of patients able to undergo MIP with shorter operative times and same-day discharge. To our knowledge, this is the first study to assess comprehensive comparative costs of pre-operative localization strategies, including the 4D-CT following indeterminate US approach. Incorporating patient preferences and comparative effects of these strategies on health-related quality of life in this patient population will be essential for future comparative effectiveness research.