A scoping review of metamodeling applications and opportunities for advanced health economic analyses

Introduction: Metamodels, also known as meta-models, surrogate models, or emulators, are used in several fields of research to negate runtime issues with analyzing computational demanding simulation models. This study introduces metamodeling and presents results of a review on metamodeling applications in health economics. Areas covered: A scoping review was performed to identify studies that applied metamodeling methods in a health economic context. After search and selection, 13 publications were found to employ metamodeling methods in health economics. Metamodels were used to perform value of information analysis (n = 5, 38%), deterministic sensitivity analysis (n = 4, 31%), model calibration (n = 1, 8%), probabilistic sensitivity analysis (n = 1), or optimization (n = 1, 8%). One study was found to extrapolate a simulation model to other countries (n = 1, 8%). Applied metamodeling techniques varied considerably between studies, with linear regression being most frequently applied (n = 7, 54%). Expert commentary: Although it has great potential to enable computational demanding analyses of health economic models, metamodeling in health economics is still in its infancy, as illustrated by the limited number of applications and the relatively simple metamodeling methods applied. Comprehensive guidance specific to health economics is needed to provide modelers with the information and tools needed to utilize the full potential of metamodels

Use of the NESS Handmaster to restore handfunction in tetraplegia: clinical experiences in ten patients

Objective: To explore possible functional effects of the Handmaster in tetraplegia and to determine suitable patients for the system. \ud \ud Patients: Patients with a cervical spinal cord injury between C4 and C6, motor group 0-3. Important selection criteria were a stable clinical situation and the absence of other medical problems and complications. \ud \ud Design: Ten patients were consecutively selected from the in- and outpatient department of a large rehabilitation hospital in The Netherlands. Each patient was fitted with a Handmaster by a qualified therapist and underwent muscle strength and functional training for at least 2 months. \ud \ud Methods: Functional evaluation comprised the performance of a defined set of tasks and at least one additional task as selected by patients themselves. Tasks were performed both with and without the Handmaster. Finally, patients were asked for their opinion on Handmaster use as well as their willingness to future use. \ud \ud Results: In six patients a stimulated grasp and release with either one or both grasp modes (key- and palmar pinch) of the Handmaster was possible. Four patients could perform the set of tasks using the Handmaster, while they were not able to do so without the Handmaster. Eventually, one patient continued using the Handmaster during ADL at home. \ud \ud Conclusion: The Handmaster has a functional benefit in a limited group of patients with a C5 SCI motor group 0 and 1. Suitable patients should have sufficient shoulder and biceps function combined with absent or weak wrist extensors. Though functional use was the main reason for using the Handmaster, this case series showed that therapeutic use can also be considered. \ud \u

Identifying the optimal use of CTCs in the early staging phase of breast cancer

Objectives: Circulating tumour cells (CTCs) in the blood can give important information about the prognosis and treatment options for cancer patients. Methods like cell-search are not sensitive enough because the blood samples are small (7,5 mL). Currently a technique is developed which can separate CTCs from the whole blood and is called the CTC Trap. This study addresses the potential impact of implementing the CTC Trap in addition to currently used imaging techniques in early staging of primary stage I-III breast cancer in women. Methods: The early staging process has been identified using the Dutch breast cancer guideline. This process is displayed in a decision tree. Three points in this process have been identified as possible implementation options for the CTC Trap. A simulation model has been built in Excel to simulate the cost-effectiveness of implementing the CTC Trap at these three different points. Results: Potentially relevant points for the CTC trap are: 1) following negative sentinel lymph node procedure to test for micro metastases, 2) following negative result of initial MRI to test for (micro-) metastases, 3) following negative results of further imaging. Usual care resulted in an average survival of 2,42 years, a 3-year survival of 93,71%, 1,51 QALYs and a cost of € 992,56. When implemented at all 3 implementation points simultaneously CTC Trap resulted in an average survival of 2,84 years, a 3-year survival of 97,46 %, 1,84 QALYS and a total cost of € 6.035,45. Conclusions: CTCs clearly have the potential to improve overall survival. Use of CTCs can potentially improve survival with 0,42 years and improve QALYs with 0,34. Costs do increase at all options but from a health economic perspective it is most valuable to implement CTC Trap in option 1) following negative sentinel lymph node procedure to test for (micro-) metastases

HElmet therapy Assessment in infants with Deformed Skulls (HEADS): protocol for a randomised controlled trial

Background In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly). However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls) aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation. Methods/design Pragmatic randomised controlled trial (RCT) nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment). At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non-randomisedrandomised controlled trial (nRCT); they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined. Discussion HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies. Besides these health outcomes, we will be able to address several methodological questions, e.g. do participants in an RCT represent the eligible target population and do outcomes of the RCT differ from outcomes found in the nRCT