Relationship Between Price and Diagnosis-Related Group Tariff for Medical Devices Assessed by a Regional Health Technology Assessment Committee.

Introduction Medical devices (MDs) make up an important share of total in-hospital expenditure. At the level of individual patients, this share is represented by the ratio of the cost of MD incurred by the patient vs. the total cost of in-hospital care for the same patient. If tariffs rather than costs are considered, the denominator of this ratio is given by the diagnosis-related group (DRG) and the ratio is the cost of MD over DRG tariff. The objective of this paper is to present a retrospective analysis comparing the ratio of price vs. DRG tariff for a group of devices belonging to risk class III or active implantable. These devices are those assessed in the years 2020 and 2021 by two committees of the Tuscany region in Italy. Materials and methods The information on price and DRG was taken from the health technology assessment (HTA) reports concerning MDs evaluated by the two above-mentioned regional committees in the years 2020 and 2021. In these reports, the information on the cost-effectiveness ratio was reported for a subset of MDs. In all cases, a preliminary qualitative assessment was carried out to determine the presence or absence of a healthcare impact in the post-discharge phase. In these preliminary analyses, the perspective of NHS was adopted. Results Our analysis was focused on 24 devices of either class III or active implantable. According to our results, a wide variability was found in the ratios between device price and DRG associated with its use. This ratio ranged from a minimum of about 3% in the case of the Hyalobarrier gel (Nordic Pharma GmbH, Zürich, Switzerland) for post-surgical adhesion to a maximum of 132% in the case of the Neovasc Reducer (EPS Vascular AB, Viken, Sweden), a device indicated in the narrowed coronary sinus. Three devices, i.e., PuraStat (3-D Matrix, Ltd., Tokyo, Japan), Ascyrus Medical Dissection Stent (AMDS, CryoLife, Inc., Kennesaw, GA), and Tendyne (Abbott Cardiovascular, Plymouth, MN), were found to be priced more than the reimbursement tariff (i.e., ratio > 100%). Ratios between 50% and 100% were found in about half of the devices. From our preliminary assessment on the presence of a post-discharge impact, 15 devices out of 24 (62%) were found to determine a substantial impact, while the remaining nine (38%) did not. In general, when costs and benefits of a device do not extend beyond the patients' discharge, the presence of a ratio > 100% reliably suggests the conclusion that the device price needs to be reduced and/or the tariff needs to be increased. On the other hand, in cases where the device extends its impact beyond the patient's hospital stay, the decision of reducing price or increasing tariff becomes more complex, and so these adjustments cannot be determined unless more information on some critical aspects is made available. Conclusions Until the above-mentioned improvements do not take place, rational interventions on DRG are virtually unfeasible owing to this lack of critical information. On the other hand, it is also difficult to intervene on device prices, again owing to the lack of critical information.

The role of medical devices in influencing in-hospital sustainability: an analysis of expenditure in 2019 vs DRG reimbursement according to major medical specialties in a region of middle Italy.

INTRODUCTION: Very limited information exists from Italian hospitals about the utilization and expenditure of medical devices. The ratio expenditure/DRG reimbursement (expressed as a percentage) is a useful parameter, particularly when it is separately calculated for each individual Azienda and, within each Azienda, according to the medical discipline. AREAS COVERED: To generate benchmarks in this area, we have made reference to the expenditure incurred for medical devices from January to June 2019 in all hospitals of the Tuscany region. These expenditures divided by medical discipline have been compared with the DRG reimbursements that hospitals receive from our Region for the same disciplines. This benchmark is represented by percent ratio expenditure/reimbursement for each of the eight Aziende and, within each Azienda, according to the medical specialty. EXPERT OPINION: These percentages indicate, for each medical discipline, to what extent medical devices typically consume the reimbursement resulting from the DRGs. These benchmarks facilitate the interpretation of values estimated locally. Determinants leading to 'excessive' values (e.g. >100%) of this parameter can include an extensive use of costly devices, a high frequency of non-remunerative procedures, the presence of inappropriate treatments, the need to update specific DRGs, deficiencies in coding expenditures and procedures, and so on.

Tenders for the Procurement of Medical Devices: Adapting Cost-Effectiveness Rules to the Requirements of the European Public Procurement Directive.

BACKGROUND: In evaluating 3 or more comparators, pharmacoeconomic analyses can be improved by using the methodology of net monetary benefit (NMB) as opposed to incremental cost-effectiveness ratio (ICER). NMB is particularly suitable for managing competitive tenders that evaluate 3 or more devices in the same lot. For scientific purposes, the methodology of NMB is perfectly adequate. However, when tenders are managed in European countries, the Public Procurement Directive states that the tender score for price should be kept separate from that of clinical benefits. As a result, the traditional mathematical approach of NMB must be rearranged to comply with this administrative requirement. METHODS: In this report, we describe how the classic equations of NMB should be modified to achieve this purpose. The mathematical principle of proportionality, which is typical of the ICER, must be replaced by the principle of mathematical additivity, which is typical of NMB. Furthermore, to rearrange the scale of benefits according to the NMB, an estimate is needed of the minimum acceptable benefit converted into monetary units, which is associated with 0 in the benefit scale. RESULTS: A detailed example is presented to explain the practical application of these mathematical equations. These equations are widely applicable in the field of implantable devices. CONCLUSION: Since the expenditure for medical devices in European hospitals is close to that of hospital medicines, tenders for the in-hospital procurement of devices may represent a decisive tool to manage sustainability and ensure access to innovation. In this context, the methodology for managing clinical outcomes through tenders requires a specific mathematical approach that we have described in the present article.

Biological meshes for abdominal hernia: Lack of evidence-based recommendations for clinical use.

BACKGROUND: In the clinical literature on abdominal hernia repair, no sound criteria have been established to support the use of biological meshes as opposed to synthetic ones. Furthermore, the information on biological meshes is quite scarce, and so their place in therapy has not yet been defined. METHODS: The treatment of primary and incisional ventral hernia was the target intervention evaluated in our analysis. Our study consisted of the following phases: a) Identification of the biologic meshes available on the market; b) Literature search focused on efficacy and safety of these meshes; c) Analysis of the findings derived from the literature search. The information collected this way was reviewed narratively, and presented according to standard meta-analysis. The main end-points of our analysis included infection of surgical wound at 1 month and recurrence at 12 months. RESULTS: Our clinical literature comprised 11 trials that evaluated 5 biological meshes: Permacol (706 patients), Strattice (324 patients), Surgisis (44 patients), Tutomesh (38 patients) and Xenmatrix (22 patients). These studies generally showed a poor methodological quality. Surgical wound infection showed a wide between-study variability (95%CI: from 12.0% to 22.9%). Also the 12-month relapse rate demonstrated a wide 95%CI (from 5.0% to 19.9%). A significantly lower rate of recurrence at 12 months was found for Permacol compared with Strattice (rate difference: -14.2%; 95%CI: -22.1% to -6.2%). DISCUSSION: Our analysis provided an overview of 5 biological meshes currently available on the market. The different types of meshes showed a marked statistical variability in the clinical outcomes. Hence, nearly all comparisons between different meshes in the two clinical end-points did not reach statistical significance. One exception was represented by the finding that cross-linked meshes had a significantly lower recurrence rate at 12 months than non-cross-linked meshes.

Value-based procurement of medical devices: Application to devices for mechanical thrombectomy in ischemic stroke.

OBJECTIVES: In the acute ischemic stroke, endovascular devices have shown promising clinical results and are also likely to represent value for money, as several modeling studies have shown. Pharmacoeconomic evaluations in this field, however, have little impact on the procurement of these devices. The present study explored how complex pharmacoeconomic models that evaluate effectiveness and cost can be incorporated into the in-hospital procurement of thrombectomy devices. PATIENTS AND METHODS: As regards clinical modeling, we extracted outcomes at three months from randomized trials conducted for four thrombectomy devices, and we projected long-term results using standard Markov modeling. In estimating QALYs, the same model was run for the four devices. As regards economic modeling, we firstly estimated for each device the net monetary benefit (NMB) per patient (threshold = $60,000 per QALY); then, we simulated a competitive tender across the four products by determining the tender-based score (on a 0-to-100 scale). Prices of individual devices were obtained from manufacturers. Extensive sensitivity testing was applied to our analyses. RESULTS: For the four devices (Solitaire, Trevo, Penumbra, Solumbra), QALYs were 1.86, 1.52, 1,79, 1.35, NMB was $101,824, $83,546, $101,923, $69,440, and tender-based scores were 99.70, 43.43, 100, 0, respectively. Sensitivity analysis confirmed findings from base-case. CONCLUSION: Our results indicate that, in the field of thrombectomy devices, incorporating the typical tools of cost-effectiveness into the processes of tenders and procurement is feasible. Bridging the methodology of cost-effectiveness with the every-day practice of in-hospital procurement can contribute to maximizing the health returns that are generated by in-hospital expenditures for medical devices.

Handling the procurement of prostheses for total hip replacement: description of an original value based approach and application to a real-life dataset reported in the UK.

OBJECTIVES: In most European countries, innovative medical devices are not managed according to cost-utility methods, the reason being that national agencies do not generally evaluate these products. The objective of our study was to investigate the cost-utility profile of prostheses for hip replacement and to calculate a value-based score to be used in the process of procurement and tendering for these devices. METHODS: The first phase of our study was aimed at retrieving the studies reporting the values of QALYs, direct cost, and net monetary benefit (NMB) from patients undergoing total hip arthroplasty (THA) with different brands of hip prosthesis. The second phase was aimed at calculating, on the basis of the results of cost-utility analysis, a tender score for each device (defined according to standard tendering equations and adapted to a 0-100 scale). This allowed us to determine the ranking of each device in the simulated tender. RESULTS: We identified a single study as the source of information for our analysis. Nine device brands (cemented, cementless, or hybrid) were evaluated. The cemented prosthesis Exeter V40/Elite Plus Ogee, the cementless device Taperloc/Exceed, and the hybrid device Exeter V40/Trident had the highest NMB (£152 877, £156 356, and £156 210, respectively) and the best value-based tender score. CONCLUSIONS: The incorporation of value-based criteria in the procurement process can contribute to optimising the value for money for THA devices. According to the approach described herein, the acquisition of these devices does not necessarily converge on the product with the lowest cost; in fact, more costly devices should be preferred when their increased cost is offset by the monetary value of the increased clinical benefit.

Non-inferiority of colistin compared with standard care for the treatment of ventilator-associated pneumonia.

This study examined the literature on the treatment of ventilator-associated pneumonia (VAP) using colistin or standard care (SC). Based on this clinical material, a meta-analysis was conducted and a non-inferiority test was performed. Studies were selected for inclusion based on the following criteria: (a) patients with VAP; (b) experimental arm based on intravenous or aerosolized colistin; and (c) control arm based on SC. The meta-analysis employed a fixed-effect model, and the endpoint was the rate of clinical response. No pre-specified non-inferiority threshold for the upper boundary of the 95% confidence interval was adopted; instead, the intention was to perform a retrospective evaluation of whether the threshold suggested by the results was acceptable on clinical grounds. In total, eight controlled studies were included. The pooled risk ratio was 1.019 for colistin compared with SC (95% confidence interval 0.895-1.16); this result corresponds to a non-significant 1.9% increase in cure rate with colistin compared with SC (range +16% to -10.5%). Heterogeneity was minimal (0%). The post-hoc non-inferiority threshold for colistin compared with SC was -10.5% in terms of relative cure rate (pooled risk ratio = 0.895). This margin was considered to be acceptable on clinical grounds. This analysis found that colistin can play a role in the treatment of VAP, particularly when given as a combination of aerosolized and intravenous drug.

"Total evidence" network meta-analysis as a tool for improving the assessment of biosimilars: application to etanercept in rheumatoid arthritis
.

Since biosimilars generally have undergone less clinical research than originators, their place in therapy can be strengthened by increasing the amount of clinical evidence supporting their approval. This report describes an approach in which a "total evidence" network meta-analysis is performed that compares the biosimilar not only with the originator but also with the previous standard of care. This analysis was retrospectively applied to etanercept biosimilar in rheumatoid arthritis (end-point = ACR50). Using an increased number of evaluated patients (1,003 for network meta-analysis vs. 596 for equivalence trial), our results confirmed the equivalence index previously estimated from the approval trial of biosimilar.
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Subcutaneous Biological Treatments for Moderate to Severe Psoriasis: Interpreting Safety Data by Network Meta-Analysis.

BACKGROUND: When multiple treatments are available, network meta-analysis can synthesize evidence and rank their relative profile in terms of effectiveness and/or safety. We applied this approach to the safety of subcutaneous biologicals used in the treatment of moderate to severe psoriasis. METHODS: Our literature search covered the articles published from January 2000 to September 2014 and was restricted to randomized controlled trials. The agents eligible for our analysis were subcutaneous biological drugs used in patients with moderate to severe psoriasis. A network meta-analysis was conducted using the Bayesian model. The analysis was aimed to compare the safety of these treatments based on 95 % credible intervals and to consequently generate a ranking in safety across the treatments. Two safety end-points were considered: any serious adverse events (AE) and any infectious AE. Risk difference was the outcome measure. The analysis estimated 95 % credible intervals for all direct and indirect comparisons as well as the ranking histogram across the treatments which was determined according to model-based probabilistic analysis. RESULTS: Our literature search selected a total of 13 randomized controlled trials of which three evaluated adalimumab, five ustekinumab (45 and 90 mg), four etanercept (both high-dose and low-dose) and one high-dose etanercept and ustekinumab (45 and 90 mg). For both end-points of any serious AE and any infectious AE, the Bayesian analysis showed no significant difference in all indirect head-to-head comparisons between active agents. For the end-point of any serious AE, the ranking was ustekinumab 45 mg and ustekinumab 90 mg (at the same rank), followed by placebo and by adalimumab and high-dose etanercept (at the same rank). For any infectious AE, the ranking was: low-dose etanercept, placebo, ustekinumab 45 mg and ustekinumab 90 mg, adalimumab and high-dose etanercept. CONCLUSION: Our analysis synthesized the current evidence on the safety of subcutaneous biological treatments for patients with moderate to severe psoriasis and was successful in defining their respective rankings.

Testing the therapeutic equivalence of novel oral anticoagulants for thromboprophylaxis in orthopedic surgery and for prevention of stroke in atrial fibrillation.

BACKGROUND: In studying the comparative effectiveness of novel oral anticoagulants (NOACs) in orthopedic surgery and in non-valvular atrial fibrillation, previous meta-analyses have found no proof of difference in head-to-head indirect comparisons between individual agents. However, the question of their therapeutic equivalence remains unanswered. OBJECTIVES: The objective of this analysis was to test the equivalence of three NOACs (dabigatran, rivaroxaban, apixaban) in orthopedic surgery and four NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) in non-valvular atrial fibrillation. METHODS: Standard pairwise meta-analysis and network meta-analysis for indirect comparisons were combined with equivalence testing. The endpoint was venous thromboembolism in orthopedic surgery and a composite of stroke or systemic embolism in atrial fibrillation. Comparisons were expressed as risk difference (RD). Margins for equivalence testing were derived from the original trials. RESULTS: Our results indicate that rivaroxaban and apixaban (but not dabigatran) are equivalent for thromboprophylaxis in orthopedic surgery. In atrial fibrillation, all the four NOACs we tested were found to meet the criterion of therapeutic equivalence. Some concern, however, is raised by some findings focused on adverse events of these agents, in which the equivalence was not proven in all analyses. CONCLUSIONS: Regardless of clinical implications, our results can be the basis to develop local acquisition tenderings on NOACS. In Italy, a new law has been issued according to which equivalence analyses have become a mandatory prerequisite for local tenderings.

Biological drugs for the treatment of rheumatoid arthritis by the subcutaneous route: interpreting efficacy data to assess statistical equivalence.

BACKGROUND: No equivalence analysis has yet been conducted on the effectiveness of biologics in rheumatoid arthritis. Equivalence testing has a specific scientific interest, but can also be useful for deciding whether acquisition tenders are feasible for the pharmacological agents being compared. METHODS: Our search covered the literature up to August 2014. Our methodology was a combination of standard pairwise meta-analysis, Bayesian network meta-analysis and equivalence testing. The agents examined for their potential equivalence were etanercept, adalimumab, golimumab, certolizumab, and tocilizumab, each in combination with methotrexate (MTX). The reference treatment was MTX monotherapy. The endpoint was ACR50 achievement at 12 months. Odds ratio was the outcome measure. The equivalence margins were established by analyzing the statistical power data of the trials. RESULTS: Our search identified seven randomized controlled trials (2846 patients). No study was retrieved for tocilizumab, and so only four biologics were evaluable. The equivalence range was set at odds ratio from 0.56 to 1.78. There were 10 head-to-head comparisons (4 direct, 6 indirect). Bayesian network meta-analysis estimated the odds ratio (with 90% credible intervals) for each of these comparisons. Between-trial heterogeneity was marked. According to our results, all credible intervals of the 10 comparisons were wide and none of them satisfied the equivalence criterion. A superiority finding was confirmed for the treatment with MTX plus adalimumab or certolizumab in comparison with MTX monotherapy, but not for the other two biologics. CONCLUSION: Our results indicate that these four biologics improved the rates of ACR50 achievement, but there was an evident between-study heterogeneity. The head-to-head indirect comparisons between individual biologics showed no significant difference, but failed to demonstrate the proof of no difference (i.e. equivalence). This body of evidence presently precludes any option of undertaking competitive tenderings for the procurement of these agents.

Intravenous proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: determining statistical equivalence according to evidence-based methods.

BACKGROUND: Although intravenous proton pump inhibitors (PPIs) are considered at least as effective as H2-receptors antagonists for stress ulcer prophylaxis (SUP) in critically ill patients, there is no data on whether there is also the proof of no difference among these agents. METHODS: The clinical material was the same as that reported in previous meta-analyses and included all trials comparing intravenous PPIs vs. H2-receptor antagonists for SUP in critically ill patients. Our methodology was a combination of meta-analysis and equivalence testing based on confidence intervals (CIs). The end-point was the rate of overt bleeding. All PPIs evaluated in the included trials were separately studied. The equivalence margins were derived from power calculation data of the original trials. RESULTS: Our analysis involved 8 randomized trials for 851 patients. Two comparisons were made (pantoprazole vs. H2-receptor antagonists and omeprazole vs. H2-receptor antagonists). The following RDs were estimated: pantoprazole, RD = -1.2%, 95% CI: -3.5% to +1.2%; omeprazole, RD = -3.0%, 95% CI: -7.2% to +1.3%. The 95% CIs confidence intervals for RDs remained within the ± 6% margin. These results indicate that intravenous pantoprazole and intravenous omeprazole are equivalent, Conclusion: These two PPIs, when administered by intravenous route, are equivalent according to reasonable equivalence margins. This conclusion can be the basis to develop local acquisition tenders on these drugs. One advantage of this approach is that the feasibility of administrative decisions can directly be tested on clinical grounds and on the basis of standard evidence-based methods.

Anti-reabsorptive agents in women with osteoporosis: determining statistical equivalence according to evidence-based methods.

BACKGROUND: In the present study, we undertook an equivalence analysis on the effectiveness of the main anti-reabsorptive agents indicated for women with osteoporosis. METHODS: Our methodology was a combination of meta-analysis (both pair-wise meta-analysis and network meta-analysis) and equivalence testing. The end-point was the incidence on new vertebral fractures. The anti-reabsorptive agents examined included alendronate, zoledronate, ibandronate, risedronate, and denosumab. RESULTS: Our analysis involved nine randomized trials. Ten head-to-head indirect comparisons were examined through network meta-analysis and the respective values of RR were estimated. The 95 % confidence intervals for RR remained within the interval of a relative ±40 % variation for all comparisons that involved alendronate, risedronate, ibandronate, and denosumab. In contrast, the comparisons involving zoledronate satisfied a post hoc margin up to ±67 %. CONCLUSION: Our results confirm that most of these anti-reabsorptive drugs (namely, alendronate, risedronate, ibandronate, and denosumab) are equivalent according to reasonable equivalence margins.