Permanent cardiac pacing using pacemaker implantation is an effective and necessary treatment for patients suffering from atrial fibrillation and bradycardia.
In this single technology assessment, we assessed a leadless pacemaker for patients indicated for single-chamber ventricular pacemaker implantation. Through design and novel technology, Medtronic's ambition is to reduce the rate of complications following pacemaker implantations.
The objective was to investigate the clinical efficacy, safety and cost effectiveness of MicraTM Transcatheter Pacing System (Micra TPS) in patients indicated for single-chamber ventricular pacemaker implantation.
We defined two alternative patient groups that may benefit from a pacemaker which can demonstrate a lower frequency of complications.
1) All patients recommended for single-chamber ventricular pacing
2) Patients recommended for single-chamber ventricular pacing, but who are at high risk for complications following pacemaker implantation.
Clinical efficacy and safety
We conducted a systematic review of the clinical efficacy and safety of the Micra TPS. The study population, intervention, comparator and outcomes (PICO) were identified in agreement with external experts and the submitter. We performed a systematic literature search to identify studies meeting our inclusion criteria. We critically appraised included studies using the Risk of Bias-tool, descriptively summarized the outcome data, and evaluated the certainty of the overall results using Grading of Recommendations Assessment, Development and Evaluation (GRADE). We also critically assessed the documentation submitted by the manufacturer to evaluate information not retrieved by our literature search.
We assessed cost‐effectiveness estimates provided by the submitter of Micra leadless pacing compared to a conventional pacing systems for patients recommended for single-chamber ventricular pacing who were at high risk for infections. A straightforward Markov cohort model was used to estimate the cost-effectiveness of the new technology compared with current practice over a 10-year time horizon, for patients aged 77. The submitted model covered the most important health outcomes and costs associated with the pacing systems. The submitter considered variations in outcomes and costs depending on which pacing system a patient receives.
We performed a separate analysis where we adjusted some of the input variables based on revised assumptions. We also ran a scenario, which was not performed by the submitter where we considered the total indicated patient population.
Clinical efficacy and safety
We identified three large multisite clinical trials with a total of 7 published articles, and three additional articles which presented single site case series with a small number of patients. All studies were prospective single-arm studies and were considered to have a high risk of bias.
The efficacy endpoints in the studies were electrical parameters and battery longevity. The results showed that after implantation, the Micra device had a pacing threshold according to the reference values (≤ 1V at 0.24 ms) in 93% and 97% of the patients, 12 and 24 months after implantation, respectively. Other electrical parameters such as pacing impedance and R-wave amplitude, as well as estimated battery longevity were shown to be consistent according to the reference values. We evaluated the technical measurements to be of low certainty due to the study design.
Safety endpoints were major clinical- and device-related complications. The two largest studies, the Micra TP Study and the Micra TPS CA Study Protocol, reported that 4% and 1.5% of patients receiving an implant had complications, respectively. These studies reported four device or system related deaths in the total population of 1 575 patients.
The complication rate was found to be lower than a historical control. However, we evaluated the evidence for this comparison to be of very low certainty, due to study design (single arm) and indirectness.
The calculated incremental cost-effectiveness ratio (ICER) based on the revised economic model for all patients recommended for single-chamber ventricular pacing, is more than 1 million NOK per QALY. The total added costs of implementing Micra to this group in Norway, would be NOK 27,386,992 in year five.
According to the objective, we also aimed to perform budget impact analyses on a sub-group of patients with high risk of complications. The submitter performed a budget impact analysis on this cohort, estimated to be 80 patients in a Norwegian setting. They estimated the total cost saving of implementing Micra to patients at high risk for complications to be NOK 724,656 in year five.
The external experts suggested that the sub-group of patients with high risk of complication would be about 10-30% of the patients with the indication in Norway. We recalculated the budget impact analysis and estimated that the total added costs of implementing Micra to patients at high risk for complications would be NOK 4,652,759 in year five. The calculated incremental cost-effectiveness ratio (ICER) based on the revised economic model for the sub-group of patients at high risk for infections was NOK 1,077,363. For this sub-population, the Micra system cannot be considered cost-effective if a threshold of NOK 500,000/QALY is applied. The performed one-way sensitivity analyses shows that relative risk of infection, the lead infection rate, the pocket infection rate and the lead infection costs have the greatest impact on the model.
Clinical efficacy and safety
The efficacy of the Micra device was measured through electrical parameters and estimation of battery longevity. The results were within the reference values given in the manual of the device and although the study design was single-arm cohort studies, we have reason to believe that the device proved its efficacy.
It is more problematic to compare the safety profile, or complication rate, of different devices only using a historical control, as in one of the major studies included in this assessment. We therefore did not have confidence in the comparative analyses presented to us through the available literature. We do acknowledge the actual numbers of complications reported in the different studies, keeping in mind the possible reporting bias and bias due to the connection between the researchers and the producer of the device.
However, we need to take into consideration the reported rate of lead and pocket complications, the most frequent complications for standard pacemakers, which obviously are not an issue if a leadless pacemaker is used.
We did not find any published economic evaluations of leadless pacemakers. However, we did not perform a systematic search of studies comparing the two types of pacemaker devices in the specific sub-group analysed in this report. The effect estimates in the economic model are therefore highly uncertain which made it difficult to make any general judgements about the potential cost-effectiveness of the intervention. The exception is that the rates of lead and pocket infection and erosion for a conventional device are likely to have a significant impact on the results. Additional benefits for a leadless pacemaker have been suggested by CADTH in an evidence summary for leadless pacemakers from 2015 (3), including shorter procedure and recovery time, reduced fluoroscopy exposure for patients and staff, no visible lump or scar, better mobility in the shoulder and expected better quality of life. These benefits were however, not quantified and evidence has not been assessed.
Despite the shortcomings of the present report, this is the first economic evaluation being performed of a leadless pacemaker, and is for the Micra device only. Any inference to other leadless pacemakers, such as the Nanostim, should not be done. There is consequently a need for further research on implications of leadless pacemakers on the health economy.
The Micra TPS is a leadless pacemaker which delivers consistent pacing as required and has a battery longevity according to the specifications for the device. The current evidence is not sufficient to prove that the Micra-TPS has fewer complications than standard pacemakers. However, the device is leadless and hence avoids all complications related to lead and pocket, which are previously reported to be in the range of 2.5-5.5% in the patient group (1;2). Published device or system related deaths were four in 1 575 implanted patients.
We looked at the budget impact of introducing Micra to all patients indicated for single chamber ventricular pacing and found that this would be a total added cost of NOK 27,386,992 in year five. The ICER for this group rises well above the level that has been considered cost-effective in Norway.
Offering the Micra device only to patients particularly susceptible to complications or who have a defined high risk of complications, may be an alternative model. Although there was no clinical evidence that the Micra may be beneficial to any specific sub-group of patients, we decided to analyse the cost-effectiveness for offering the Micra device to patients with a high risk of complications, and more specifically, with a high risk of infection. This group was estimated to be 10-30% of the total indicated patients. The analysis shows that the total added cost will be about NOK 4,652,759 in year five, by introducing Micra to this group in a Norwegian setting. After adjusting the model to account for important shortcomings in the submitted analysis, related to clinical effect input data, the ICER is considered to be not cost-effective for this sub-group.