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Radboud University, 09 maart 2023, Promotor : Rovers, M.M. Co-promotor : Grutters, J.P.C., Contains fulltext : 289593.pdf (Publisher’s version ) (Closed access)

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Radboud University, 10 februari 2023, Promotores : Witjes, J.A., Rovers, M.M. Co-promotor : Hannink, G.J., Contains fulltext : 288658.pdf (Publisher’s version ) (Closed access)

Radboud University, 20 januari 2023, Promotores : Rosman, C., Rovers, M.M., Contains fulltext : 286398.pdf (Publisher’s version ) (Open Access)

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01 april 2023, Item does not contain fulltext, PURPOSE: Navigation has been suggested to guide complex benign bone tumor curettage procedures, but the contribution of navigation to the accuracy of curettage has never been quantified. We explored the accuracy of navigated curettage in a cadaveric observational pilot study, comparing navigated to freehand curettage, performed independently by an expert and a novice user. METHODS: The expert performed curettage on 20 cadaveric bones prepared with a paraffin wax mixture tumor, 10 freehand and 10 navigated. We re-used 12 bones for the novice experiments, 6 freehand and 6 navigated. Tumor and curettage cavity volumes were segmented on pre- and post-cone-beam CT scans. Accuracy was quantified using the Dice Similarity Coefficient (DSC), and with remaining tumor volume, bone curettage volume, maximal remaining width and procedure times compared between navigation and freehand groups for both users. RESULTS: There were little differences in curettage accuracy between a navigated (DSC 0.59[0.17]) and freehand (DSC 0.64[0.10]) approach for an expert user, but there were for a novice user with DSC 0.67(0.14) and 0.83(0.06), respectively. All navigated and freehand procedures had some amount of remaining tumor, generally located in a few isolated spots with means of 2.2(2.6) cm(3) (mean 20% of the tumor volume) and 1.5(1.4) cm(3) (18%), respectively, for the expert and more diffusely spaced with means of 5.1(2.8) cm(3) (33%) and 3.0(2.2) cm(3) (17%), respectively, for the novice. CONCLUSIONS: In an explorative study on 20 cadaveric bone tumor models, navigated curettage in its current setup was not more accurate than freehand curettage. The amount of remaining tumor, however, confirms that curettage could be further improved. The novice user was less accurate using navigation than freehand, which could be explained by the learning curve. Furthermore, the expert used a different surgical approach than the novice, focusing more on removing the entire tumor than sparing surroun

Contains fulltext : 295988.pdf (Publisher’s version ) (Closed access), OBJECTIVE: The aim of this study was to determine if prophylactic mesh placement is an effective, safe, and cost-effective procedure to prevent parastomal hernia (PSH) formation in the long term. BACKGROUND: A PSH is the most frequent complication after stoma formation. Prophylactic placement of a mesh has been suggested to prevent PSH, but long-term evidence to support this approach is scarce. METHODS: In this multicentre superiority trial patients undergoing the formation of a permanent colostomy were randomly assigned to either retromuscular polypropylene mesh reinforcement or conventional colostomy formation. Primary endpoint was the incidence of a PSH after 5 years. Secondary endpoints were morbidity, mortality, quality of life, and cost-effectiveness. RESULTS: A total of 150 patients were randomly assigned to the mesh group (n = 72) or nonmesh group (n = 78). For the long-term follow-up, 113 patients were analyzed, and 37 patients were lost to follow-up. After a median follow-up of 60 months (interquartile range: 48.6-64.4), 49 patients developed a PSH, 20 (27.8%) in the mesh group and 29 (37.2%) in the nonmesh group ( P = 0.22; RD: -9.4%; 95% CI: -24, 5.5). The cost related to the meshing strategy was € 2.239 lower than the nonmesh strategy (95% CI: 491.18, 3985.49), and quality-adjusted life years did not differ significantly between groups ( P = 0.959; 95% CI: -0.066, 0.070). CONCLUSIONS: Prophylactic mesh placement during the formation of an end-colostomy is a safe procedure but does not reduce the incidence of PSH after 5 years of follow-up. It does, however, delay the onset of PSH without a significant difference in morbidity, mortality, or quality of life, and seems to be cost-effective.

Contains fulltext : 296056.pdf (Publisher’s version ) (Open Access), BACKGROUND: Glioblastoma (GBM) is the most common primary, malignant brain tumour with a 5-year survival of 5%. If possible, a glioblastoma is resected and further treated with chemoradiation therapy (CRT), but resection is not feasible in about 30% of cases. Current standard of care in these cases is a biopsy followed by CRT. Magnetic resonance (MR) imaging-guided laser interstitial thermal therapy (LITT) has been suggested as a minimally invasive alternative when surgery is not feasible. However, high-quality evidence directly comparing LITT with standard of care is lacking, precluding any conclusions on (cost-)effectiveness. We therefore propose a multicenter randomized controlled study to assess the (cost-)effectiveness of MR-guided LITT as compared to current standard of care (EMITT trial). METHODS AND ANALYSIS: The EMITT trial will be a multicenter pragmatic randomized controlled trial in the Netherlands. Seven Dutch hospitals will participate in this study. In total 238 patients will be randomized with 1:1 allocation to receive either biopsy combined with same-session MR-guided LITT therapy followed by CRT or the current standard of care being biopsy followed by CRT. The primary outcomes will be health-related quality of life (HR-QoL) (non-inferiority) using EORTC QLQ-C30 + BN20 scores at 5 months after randomization and overall survival (superiority). Secondary outcomes comprise cost-effectiveness (healthcare and societal perspective) and HR-QoL of life over an 18-month time horizon, progression free survival, tumour response, disease specific survival, longitudinal effects, effects on adjuvant treatment, ablation percentage and complication rates. DISCUSSION: The EMITT trial will be the first RCT on the effectiveness of LITT in patients with glioblastoma as compared with current standard of care. Together with the Dutch Brain Tumour Patient association, we hypothesize that LITT may improve overall survival without substantially affecting patients' quality o

Contains fulltext : 296153.pdf (Publisher’s version ) (Open Access), BACKGROUND: A previous individual participant data meta-analysis (IPD-MA) of antibiotics for adults with clinically diagnosed acute rhinosinusitis (ARS) showed a marginal overall effect of antibiotics, but was unable to identify patients that are most likely to benefit from antibiotics when applying conventional (i.e. univariable or one-variable-at-a-time) subgroup analysis. We updated the systematic review and investigated whether multivariable prediction of patient-level prognosis and antibiotic treatment effect may lead to more tailored treatment assignment in adults presenting to primary care with ARS. METHODS: An IPD-MA of nine double-blind placebo-controlled trials of antibiotic treatment (n=2539) was conducted, with the probability of being cured at 8-15 days as the primary outcome. A logistic mixed effects model was developed to predict the probability of being cured based on demographic characteristics, signs and symptoms, and antibiotic treatment assignment. Predictive performance was quantified based on internal-external cross-validation in terms of calibration and discrimination performance, overall model fit, and the accuracy of individual predictions. RESULTS: Results indicate that the prognosis with respect to risk of cure could not be reliably predicted (c-statistic 0.58 and Brier score 0.24). Similarly, patient-level treatment effect predictions did not reliably distinguish between those that did and did not benefit from antibiotics (c-for-benefit 0.50). CONCLUSIONS: In conclusion, multivariable prediction based on patient demographics and common signs and symptoms did not reliably predict the patient-level probability of cure and antibiotic effect in this IPD-MA. Therefore, these characteristics cannot be expected to reliably distinguish those that do and do not benefit from antibiotics in adults presenting to primary care with ARS.

Contains fulltext : 295981.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: There is a wide variety of participatory approaches to involve stakeholders in the development of medical devices, but there is no comprehensive overview of these approaches. We therefore studied what participatory approaches are used in the development of medical devices as well as the most important characteristics and challenges of these approaches. METHODS: We conducted a scoping review and searched PubMed, Embase and Web of Science for articles published between July 2014 and July 2019. Papers were included if they presented original research featuring any form of stakeholder participation in the development of medical devices. We used The Spectrum of Public Participation to categorise the approach of each paper. Subsequently, we described the characteristics of each approach: the stakeholders involved, data collection methods, and topics addressed. We also identified challenges of the approaches as reported by researchers. RESULTS: 277 papers were included, which could be categorised into three levels of participation: collaboration, involvement, and consultation. Patients and healthcare professionals are frequently engaged in all approaches. The most often used methods are workshops in the collaboration approach papers, and interviews in the involvement and consultation approach papers. Topics addressed in all approaches are: the problem, device requirements, design choices, testing, and procedural aspects of involvement. Reported challenges entail issues related to sampling, analysis, social dynamics, feasibility, and the limited number of topics that can be addressed. CONCLUSION: Participatory approaches reported in literature can be categorised in three overarching approaches that have comparable methodological characteristics. This suggests that if researchers want to apply a participatory approach it is not necessary to adopt a pre-determined approach, such as 'participatory action research' (PAR). Instead, they can independently determine th

Item does not contain fulltext, The use of invasive placebo controls in surgical trials can be challenging. The ASPIRE guidance, published in the Lancet in 2020, provided advice for the design and conduct of surgical trials with an invasive placebo control. Based on a more recent international expert workshop in June 2022, we now provide further insights into this topic. These include the purpose and design of invasive placebo controls, patient information provision and how findings from these trials may be used to inform decision-making.

Contains fulltext : 294358.pdf (Publisher’s version ) (Open Access), INTRODUCTION: In the last decades, the application of stereotactic laser ablation (SLA) for the treatment of intracranial tumours has been growing, even though comparative trials are lacking. Our aim was to investigate the familiarity with SLA of neurosurgeons in Europe and their opinion regarding potential neuro-oncological indications. Furthermore, we investigated treatment preferences and variability for three exemplar neuro-oncological cases and willingness to refer for SLA. MATERIAL AND METHODS: A 26-questions survey was mailed to members of the EANS neuro-oncology section. We presented three clinical cases of respectively deep-seated glioblastoma, recurrent metastasis and recurrent glioblastoma. Descriptive statistics was applied to report results. RESULTS: 110 respondents completed all questions. Recurrent glioblastoma and recurrent metastases were regarded as the most feasible indications for SLA (chosen by 69% and 58% of the respondents) followed by newly diagnosed high-grade gliomas (31%). Seventy percent of respondents would refer patients for SLA. The majority of respondents would consider SLA as a treatment option for all three presented cases: 79% for the deep-seated glioblastoma case, 65% for the recurrent metastasis case and 76% for the recurrent glioblastoma case. Among respondents who wouldn't consider SLA, preference for standard treatment and lack of clinical evidence were reported as the main reasons. CONCLUSIONS: Most of respondents considered SLA as a treatment option for recurrent glioblastoma, recurrent metastases and newly diagnosed deep-seated glioblastoma. At the moment the current evidence to support such a treatment is very low. Comparative prospective trials are needed to support the use of SLA and determine proper indications.

Contains fulltext : 299839.pdf (Publisher’s version ) (Open Access), OBJECTIVES: Identifying unmet needs for innovative solutions across disease contexts is challenging but important for directing funding and research efforts and informing early-stage decisions during the innovation process. Our aim was to study the merits of care pathway analysis to scope disease contexts and guide the development of innovative devices. We used oncologic surgery as a case study, for which many intraoperative imaging techniques are under development. METHODS: Care pathway analysis is a mapping process, which produces graphical maps of clinical pathways using important outcomes and subsequent consequences. We performed care pathway analyses for glioblastoma, breast, bladder, prostate, renal, pancreatic, and oral cavity cancer. Differences between a "perfect" care pathway and the current care pathway in terms of percentage of inadequate margins, associated recurrences, quality of life, and 5-year overall survival were calculated to determine unmet needs. Data from The Netherlands Cancer Registry and literature were used. RESULTS: Care pathway analysis showed that highest percentages of inadequate margins were found in oral cavity cancer (72.5%), glioblastoma (48.7%), and pancreatic cancer (43.9%). Inadequate margins showed the strongest increase in recurrences in cancer of oral cavity, and bladder (absolute increases of 43.5% and 41.2%, respectively). Impact on survival was largest for bladder and oral cavity cancer with positive margins. CONCLUSIONS: Care pathway analysis provides overviews of current clinical paths in multiple indications. Disease contexts can be compared via effectiveness gaps that show the potential need for innovative solutions. This information can be used as basis for stakeholder involvement processes to prioritize care pathways in need of innovation., 01 december 2023

Contains fulltext : 299880.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: Concerns exist regarding the generalizability of results from randomized controlled trials (RCTs) evaluating arthroscopic partial meniscectomy (APM) to treat degenerative meniscus tears. It has been suggested that study populations are not representative of subjects selected for surgery in daily clinical practice. Therefore, we aimed to compare patients included in trials and prospective cohort studies that received APM for a degenerative meniscus tear. PATIENTS AND METHODS: Individual participant data from 4 RCTs and 2 cohort studies undergoing APM were collected. 1,970 patients were analyzed: 605 patients included in RCTs and 1,365 included in the cohorts. We compared patient and disease characteristics, knee pain, overall knee function, and health-related quality of life at baseline between the RCT and cohort groups using standardized differences, ratios comparing the variance of continuous covariates, and graphical methods such as quantile-quantile plots, side-by-side boxplots, and non-parametric density plots. RESULTS: Differences between RCT and the cohort were observed primarily in age (younger patients in the cohort; standardized difference: 0.32) and disease severity, with the RCT group having more severe symptoms (standardized difference: 0.38). While knee pain, overall knee function, and quality of life generally showed minimal differences between the 2 groups, it is noteworthy that the largest observed difference was in knee pain, where the cohort group scored 7 points worse (95% confidence interval 5-9, standardized difference: 0.29). CONCLUSION: Patients in RCTs were largely representative of those in cohort studies regarding baseline scores, though variations in age and disease severity were observed. Younger patients with less severe osteoarthritis were more common in the cohort; however, trial participants still appear to be broadly representative of the target population.

01 september 2023, Contains fulltext : 296922.pdf (Publisher’s version ) (Open Access), PURPOSE: Laser interstitial thermal therapy (LITT) is increasingly being used in the treatment of brain tumors, whereas high-quality evidence of its effectiveness is lacking. This pilot examined the feasibility of conducting a randomized controlled trial (RCT) in patients with irresectable newly diagnosed glioblastoma (nGBM), and generated data on technical feasibility and safety. METHODS: We included patients with irresectable nGBM with KPS ≥ 70 and feasible trajectories to ablate ≥ 70% of the tumor volume. Patients were initially randomized to receive either biopsy combined with LITT or biopsy alone, followed by chemoradiation (CRT). Randomization was stopped after 9 patients as the feasibility endpoint with respect to willingness to be randomized was met. Main endpoints were feasibility of performing an RCT, technical feasibility of LITT and safety. Follow-up was 3 months. RESULTS: A total of 15 patients were included, of which 10 patients received a biopsy followed by LITT and 5 patients a biopsy. Most patients were able to complete the follow-up procedures (93% clinical, 86% questionnaires, 78% MRI). Patients were planned within 3 weeks after consultation (median 12 days, range 8-16) and no delay was observed in referring patients for CRT (median 37 days, range 28-61). Two CD ≥ 3 complications occurred in the LITT arm and none in the biopsy arm. CONCLUSION: An RCT to study the effectiveness of LITT in patients with an irresectable nGBM seems feasible with acceptable initial safety data. The findings from this pilot study helped to further refine the design of a larger full-scale multicenter RCT in the Netherlands. Protocol and study identifier: The current study is registered at clinicaltrials.gov (EMITT pilot study, NTR: NCT04596930).

Item does not contain fulltext, CONTEXT: Focal therapy is a promising, minimally invasive strategy to selectively treat localized prostate cancer. A previous systematic review indicated that there is growing evidence for favorable functional outcomes, but that oncological effectiveness was yet to be defined. OBJECTIVE: To assess the effectiveness of focal therapy in patients with localized prostate cancer in terms of functional and oncological outcomes. EVIDENCE ACQUISITION: PubMed, Embase, and The Cochrane Library were searched for studies between October 2015 and December 31, 2020. In addition, the research stages were acquired according to the Idea, Development, Exploration, Assessment, Long-term study (IDEAL) recommendations. Ongoing studies were identified through clinical trial registries. EVIDENCE SYNTHESIS: Seventy-two studies were identified exploring eight different sources of energy to deliver focal therapy in 5827 patients. Twenty-seven studies reported on high-intensity focused ultrasound (HIFU), nine studies on irreversible electroporation, 11 on cryoablation, eight on focal laser ablation and focal brachytherapy, seven on photodynamic therapy (PDT), two on radiofrequency ablation, and one on prostatic artery embolization. The majority of studies were prospective development stage 2a studies (n = 357). PDT and HIFU, both in stage 3, showed promising results. Overall, HIFU studies reported a median of 95% pad-free patients and a median of 85% patients with no clinically significant cancer (CSC) in the treated area. For PDT, no changes in continence were reported and a median of 90% of patients were without CSC. Both treatments were well tolerated. CONCLUSIONS: Over the past 5 yr, focal therapy has been studied for eight different energy sources, mostly in single-arm stage 2 studies. Although a first randomized controlled trial in focal therapy has been performed, more high-quality evaluations are needed, preferably via multicenter randomized controlled trials with long-term follow-up

Contains fulltext : 248591.pdf (Publisher’s version ) (Open Access), PURPOSE: To develop a diagnostic model to identify patients at high risk of a CPA lesion. METHODS: A consecutive cohort of patients with AAD referred by a general practitioner, who underwent their first MRI examination of the CPA between 2005 and 2015 was included. Demographics, symptoms, findings during physical examination, and pure-tone audiometry were used as potential predictors. The presence of a CPA lesion was used as outcome. RESULTS: We analyzed data of 2,214 patients, detecting 73 CPA lesions in 69 (3.1%) patients. The final model contained eleven variables, namely gender [male] [OR 1.055 (95% CI 0.885-1.905)], sudden onset of hearing loss [OR 0.768 (95% CI 0.318-0.992)], gradual onset of hearing loss [OR 1.069 (95% CI 0.500-1.450)], unilateral tinnitus [OR 0.682 (95% CI 0.374-0.999)], complaints of unilateral aural fullness [OR 1.006 (95% CI 0.783-2.155)], instability [OR 1.006 (95% CI 0.580-2.121)], headache [OR 0.959 (95% CI 0.059-1.090)], facial numbness [OR 2.746 (95% CI 0.548-11.085)], facial nerve dysfunction during physical examination [OR 1.024 (95% CI 0.280-3.702)], and asymmetry in BC at 1 kHz [OR 1.013 (95% CI 1.000-1.027)] and 4 kHz [OR 1.008 (95% CI 1.000-1.026)]. CONCLUSION: The proposed diagnostic model is a first step in selecting patients with a high risk of a CPA lesion among those with AAD. It needs to be externally validated prior to its implementation in clinical practice.

Item does not contain fulltext, OBJECTIVE: To extend the IDEAL framework for device innovation, IDEAL-D, to include the preclinical stage of development (stage 0). BACKGROUND: In previous work, the IDEAL collaboration has proposed frameworks for new surgical techniques and complex therapeutic technologies, the central tenet being that development and evaluation can and should proceed together in an ordered and logical manner that balances innovation and safety. METHODS: Following agreement at the IDEAL Collaboration Council, a multidisciplinary working group was formed comprising 12 representatives from healthcare, academia, industry, and a patient advocate. The group conducted a series of discussions following the principles used in the development of the original IDEAL framework. Importantly, IDEAL aims for maximal transparency, optimal validity in the evaluation of primary effects, and minimization of potential risk to patients or others. The proposals were subjected to further review and editing by members of the IDEAL Council before a final consensus version was adopted. RESULTS: In considering which studies are required before a first-in-human study, we have: (1) classified devices according to what they do and the risks they carry, (2) classified studies according to what they show about the device, and (3) made recommendations based on the principle that the more invasive and high risk a device is, the greater proof required of their safety and effectiveness before progression to clinical studies (stage 1). CONCLUSIONS: The proposed recommendations for preclinical evaluation of medical devices represent a proportionate and pragmatic approach that balances the de-risking of first-in-human translational studies against the benefits of rapid translation of new devices into clinical practice.

Contains fulltext : 248673.pdf (Publisher’s version ) (Open Access), BACKGROUND: Over the past decade, many hospitals have adopted hybrid operating rooms (ORs). As resources are limited, these ORs have to prove themselves in adding value. Current estimations on standard OR costs show great variety, while cost analyses of hybrid ORs are lacking. Therefore, this study aims to identify the cost drivers of a conventional and hybrid OR and take a first step in evaluating the added value of the hybrid OR. METHODS: A comprehensive bottom-up cost analysis was conducted in five Dutch hospitals taking into account: construction, inventory, personnel and overhead costs by means of interviews and hospital specific data. The costs per minute for both ORs were calculated using the utilization rates of the ORs. Cost drivers were identified by sensitivity analyses. RESULTS: The costs per minute for the conventional OR and the hybrid OR were €9.45 (€8.60-€10.23) and €19.88 (€16.10- €23.07), respectively. Total personnel and total inventory costs had most impact on the conventional OR costs. For the hybrid OR the costs were mostly driven by utilization rate, total inventory and construction costs. The results were incorporated in an open access calculation model to enable adjustment of the input parameters to a specific hospital or country setting. CONCLUSION: This study estimated a cost of €9.45 (€8.60-€10.23) and €19.88 (€16.10-€23.07) for the conventional and hybrid OR, respectively. The main factors influencing the OR costs are: total inventory costs, total construction costs, utilization rate, and total personnel costs. Our analysis can be used as a basis for future research focusing on evaluating value for money of this promising innovative OR. Furthermore, our results can inform surgeons, and decision and policy-makers in hospitals on the adoption and optimal utilization of new (hybrid) ORs.

Contains fulltext : 248586.pdf (Publisher’s version ) (Open Access), OBJECTIVES: To adjust for confounding in observational data, researchers use propensity score matching (PSM), but more advanced methods might be required when dealing with longitudinal data and time-varying treatments as PSM might not include possible changes that occurred over time. This study aims to explore which confounding adjustment methods have been used in longitudinal observational data to estimate a treatment effect and identify potential inappropriate use of PSM. DESIGN: Mapping review. DATA SOURCES: We searched PubMed, from inception up to January 2021, for studies in which a treatment was evaluated using longitudinal observational data. ELIGIBILITY CRITERIA: Methodological, non-medical and cost-effectiveness papers were excluded, as were non-English studies and studies that did not study a treatment effect. DATA EXTRACTION AND SYNTHESIS: Studies were categorised based on time of treatment: at baseline (interventions performed at start of follow-up) or time-varying (interventions received asynchronously during follow-up) and sorted based on publication year, time of treatment and confounding adjustment method. Cumulative time series plots were used to investigate the use of different methods over time. No risk-of-bias assessment was performed as it was not applicable. RESULTS: In total, 764 studies were included that met the eligibility criteria. PSM (165/201, 82%) and inverse probability weighting (IPW; 154/502, 31%) were most common for studies with a treatment at baseline (n=201) and time-varying treatment (n=502), respectively. Of the 502 studies with a time-varying treatment, 123 (25%) used PSM with baseline covariates, which might be inappropriate. In the past 5 years, the proportion of studies with a time-varying treatment that used PSM over IPW increased. CONCLUSIONS: PSM is the most frequently used method to correct for confounding in longitudinal observational data. In studies with a time-varying treatment, PSM was potentially inappropriately u

Item does not contain fulltext, BACKGROUND: Endoscopic sinus surgery (ESS) is a common operation for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) when medical therapy alone is insufficient. No randomised controlled trials on the efficacy of ESS have been published. We aimed to assess the efficacy of ESS plus medical therapy versus medical therapy alone in patients with CRSwNP. METHODS: We performed an open-label, multicentre, pragmatic, randomised, controlled trial in three tertiary care centres and 12 secondary care centres in 11 cities in the Netherlands (Almere, Amstelveen, Amsterdam, Blaricum, Den Haag, Deventer, Haarlem, Hoofddorp, Hoorn, Leiderdorp, and Rotterdam). Adults (aged ≥18 years) with CRSwNP and an indication for ESS were randomly assigned (1:1) using block randomisation (block sizes of six), stratified by study centre, to receive either ESS plus medical therapy or medical therapy. ESS was performed according to local practice, although anterior ethmoidectomy was mandatory. Medical therapy was prescribed at the patient's otorhinolaryngologist's discretion, and could be, but was not limited to, nasal corticosteroids, nasal rinsing, systemic corticosteroids, or systemic antibiotics. The primary outcome was disease-specific health-related quality of life (HRQoL) at 12 months of follow up, measured with the validated Sinonasal Outcome Test 22 (SNOT-22; where each item is scored from 0 to 5, where 0 indicated no problems and 5 indicates problems as bad as can be, with a total score of 0-110 points), and the minimal clinically important difference of the SNOT-22 is 9·0 points. Primary and safety analyses were performed on an intention-to-treat (ITT) basis. The ITT population comprised all patients who were randomly assigned to treatment according to their randomisation group and without any protocol violation. This study is registered with the Netherlands Trial Register, NTR4978, and is ongoing. FINDINGS: Between Feb 15, 2015, and Aug 27, 2019, 371 patients were screene

Item does not contain fulltext, OBJECTIVES: To determine the cost-effectiveness of auditory brainstem response prior to MRI (ABR-MRI) compared to standalone MRI to diagnose vestibular schwannoma. DESIGN: A state transition model was developed to simulate costs and effects (quality-adjusted life years [QALY]) for both diagnostic strategies for patients suspected of a vestibular schwannoma. Model input was derived from literature, hospital databases and expert opinions. Scenario and sensitivity analyses addressed model uncertainty. RESULTS: Over a lifetime horizon, ABR-MRI resulted in a limited cost-saving of €68 or €98 per patient (dependent on MRI sequence) and a health loss of 0.005 QALYs over standalone MRI. ABR-MRI, however, did miss patients with other important pathology (2% of the population) that would have been detected when using standalone MRI. In total, €14 203 or €19 550 could be saved per lost QALY if ABR-MRI was used instead of standalone MRI. The results were sensitive to the detection rate of vestibular schwannoma and health-related quality of life of missed patients. CONCLUSION: The cost-saving with ABR-MRI does not seem to outweigh the number of missed patients with VS and other important pathologies that would have been detected when using standalone MRI.

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Contains fulltext : 248580.pdf (Publisher’s version ) (Open Access), OBJECTIVE: The aim of this study was to develop an evidence-based framework for evaluation of therapeutic devices, based on ethical principles and clinical evidence considerations. SUMMARY BACKGROUND DATA: Nearly all medical products which do not work solely through chemical action are regulated as medical devices. Their huge range of purposes, mechanisms of action and risks pose challenges for regulation. High-profile implantable device failures have fuelled concerns about the level of clinical evidence needed for market approval. Calls for more rigorous evaluation lack clarity about what kind of evaluation is appropriate, and are commonly interpreted as meaning more randomized controlled trials (RCTs). These are valuable where devices are genuinely new and claim to offer measurable therapeutic benefits. Where this is not the case, RCTs may be inappropriate and wasteful. METHODS: Starting with a set of ethical principles and basic precepts of clinical epidemiology, we developed a sequential decision-making algorithm for identifying when an RCT should be performed to evaluate new therapeutic devices, and when other methods, such as observational study designs and registry-based approaches, are acceptable. RESULTS: The algorithm clearly defines a group of devices where an RCT is deemed necessary, and the associated framework indicates that an IDEAL 2b study should be the default clinical evaluation method where it is not. CONCLUSIONS: The algorithm and recommendations are based on the principles of the IDEAL-D framework for medical device evaluation and appear eminently practicable. Their use would create a safer system for monitoring innovation, and facilitate more rapid detection of potential hazards to patients and the public.

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Item does not contain fulltext, BACKGROUND: The shift from open to minimally invasive procedures with growing complexity has increased the demand for advanced intraoperative medical technologies. The hybrid operating room (OR) combines the functionality of a standard OR with fixed advanced imaging systems to facilitate minimally invasive image-guided procedures. OBJECTIVE: This systematic scoping review provides an overview of the use of the hybrid OR over the years, and reports on the encountered advantages and challenges. METHODS: We conducted a systematic search in PubMed, Embase, Web of Science, and Cochrane library databases for studies that described procedures being performed with the aid of 3D imaging in the hybrid OR. RESULTS: The search identified 123 studies that described 44 distinct procedures, divided over nine clinical disciplines. The number of studies increased from two in 2010 to 15 in the first five months of 2020. Ninety-nine (80%) of the studies described how 3D imaging was performed in the hybrid OR; 95 (96%) used cone-beam CT; four (4%) used multi-detector CT. Advantages and challenges of the hybrid OR were described in 94 (76%) and 34 (35%) studies, respectively. The most frequently reported advantage of using a hybrid OR is the achievement of more accurate treatment results, whereas elongation of the procedure time is the most important challenge, followed by an increase in radiation dose. CONCLUSION: In conclusion, the growing number of clinical disciplines that uses the hybrid OR shows its wide functionality. To optimize its use, future comparative studies should be conducted to investigate which procedures really benefit from being performed in the hybrid OR.

Radboud University, 10 juni 2022, Promotores : Listl, M.S., Rovers, M.M., Contains fulltext : 250096.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 248595.pdf (Publisher’s version ) (Open Access), BACKGROUND: Health systems face challenges to accelerate access to innovations that add value and avoid those unlikely to do so. This is very timely to the field of age-related sensorineural hearing loss (ARHL), where a significant unmet market need has been identified and sizeable investments made to promote the development of novel hearing therapeutics (NT). This study aims to apply health economic modeling to inform the development of cost-effective NT. METHODS: We developed a decision-analytic model to assess the potential costs and effects of using regenerative NT in patients ≥50 with ARHL. This was compared to the current standard of care including hearing aids and cochlear implants. Input data was collected from systematic literature searches and expert opinion. A UK NHS healthcare perspective was adopted. Three different but related analyses were performed using probabilistic modeling: (1) headroom analysis, (2) scenario analyses, and (3) threshold analyses. RESULTS: The headroom analysis shows an incremental net monetary benefit (iNMB) of £20,017[£11,299-£28,737] compared to the standard of care due to quality-adjusted life-years (QALY) gains and cost savings. Higher therapeutic efficacy and access for patients with all degrees of hearing loss yields higher iNMBs. Threshold analyses shows that the ceiling price of the therapeutic increases with more severe degrees of hearing loss. CONCLUSION: NT for ARHL are potentially cost-effective under current willingness-to-pay (WTP) thresholds with considerable room for improvement in the current standard of care pathway. Our model can be used to help decision makers decide which therapeutics represent value for money and are worth commissioning, thereby paving the way for urgently needed NT.

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Contains fulltext : 283292.pdf (Publisher’s version ) (Closed access)

Radboud University, 05 oktober 2022, Promotor : Rovers, M.M. Co-promotores : Grutters, J.P.C., Hannink, G.J., Contains fulltext : 273913.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 251358.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Objectives To determine if cone beam CT-guided navigation bronchoscopy (CBCT-NB) is a cost-effective diagnostic procedure in patients with a pulmonary nodule (PN) with an intermediate risk for lung cancer. Materials and methods Two decision analytical models were developed to compare the long-term costs, survival and quality of life. In the first model, CBCT-NB was compared with CT-guided transthoracic needle biopsy (TTNB) in TTNB eligible patients. In the second model, CBCT-NB was compared with direct treatment (without pathology proven lung cancer) in patients for whom TTNB is not suitable. Input data were gathered in-house, from literature and expert opinion. Effects were expressed in quality-adjusted life years (QALYs). Sensitivity analyses were used to assess uncertainty. Results CBCT-NB can be cost-effective in TTNB eligible patients with an incremental cost-effectiveness ratio of euro18 416 in an expert setting. The probabilistic sensitivity analysis showed that in 69% and 90% of iterations CBCT-NB remained cost-effective assuming a willingness to pay (WTP) of euro20 000 and euro80 000 per QALY. CBCT-NB dominated in the treatment strategy in which TTNB is not suitable. The probabilistic sensitivity analysis showed that in 95% of iterations CBCT-NB remained the dominant strategy, and CBCT-NB remained cost-effective in 100% of iterations assuming a WTP limit of euro20 000. In the comparison between CBCT NB and TTNB, the deterministic sensitivity analysis showed that the diagnostic properties and costs of both procedures have a large impact on the outcome. Conclusions CBCT-NB seems a cost-effective procedure when compared with TTNB and when compared with a direct treatment strategy in patients with an intermediate risk PN.

Item does not contain fulltext, BACKGROUND: Open radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. OBJECTIVE: To assess the cost-effectiveness of RARC compared to ORC in bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. RESULTS AND LIMITATIONS: The mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791-€18 720) for ORC and €21 266 (95% CI €19 163-€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431-€22 642) for ORC and €24 896 (95% CI €21 925-€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74-0.85) compared to 0.81 QALYs (95% CI 0.77-0.85) for ORC patients, resulting in a mean QALY difference of -0.02 (95% CI -0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and soc

Item does not contain fulltext, Randomized trials typically estimate average relative treatment effects, but decisions on the benefit of a treatment are possibly better informed by more individualized predictions of the absolute treatment effect. In case of a binary outcome, these predictions of absolute individualized treatment effect require knowledge of the individual's risk without treatment and incorporation of a possibly differential treatment effect (ie, varying with patient characteristics). In this article, we lay out the causal structure of individualized treatment effect in terms of potential outcomes and describe the required assumptions that underlie a causal interpretation of its prediction. Subsequently, we describe regression models and model estimation techniques that can be used to move from average to more individualized treatment effect predictions. We focus mainly on logistic regression-based methods that are both well-known and naturally provide the required probabilistic estimates. We incorporate key components from both causal inference and prediction research to arrive at individualized treatment effect predictions. While the separate components are well known, their successful amalgamation is very much an ongoing field of research. We cut the problem down to its essentials in the setting of a randomized trial, discuss the importance of a clear definition of the estimand of interest, provide insight into the required assumptions, and give guidance with respect to modeling and estimation options. Simulated data illustrate the potential of different modeling options across scenarios that vary both average treatment effect and treatment effect heterogeneity. Two applied examples illustrate individualized treatment effect prediction in randomized trial data.

Contains fulltext : 233506.pdf (Publisher’s version ) (Open Access)

Radboud University, 09 december 2021, Promotores : Rosman, C., Rovers, M.M., Contains fulltext : 231288.pdf (Publisher’s version ) (Open Access)