Adoption of product service systems in health care.

Health care systems are constantly challenged to deliver better quality of care at lower cost. Product Services Systems (PSS) aim to output a higher value to a customer, while reducing resource input required to achieve such value and sustainability. In the health care market this could help companies increase their focus on value for the patient, but also for the health care system as such. This focus on value can ultimately help drive down health care cost, which is one of the most pressing issues in health care systems today. The potential of PSS to address some of the major challenges in the health care market was recognised early in PSS research, however adoption in this field is still below expectation. Motivated by the potential of PSS in health care this work aims to explore the current status of adoption as well as drivers and barriers to future adoption in this market and evaluates if and how PSS can be designed and implemented by companies active in this market. This work showed that PSS can be feasible and useful in this sector as they address relevant current challenges. Future changes in the health care market will likely make PSS even more relevant. Certain concepts of PSS are already applied in the market without leveraging the benefits of a fully developed PSS. Limitations in how the value for patients and other market actors is determined and made transparent is a major challenge in the adoption of PSS. An assessment method is proposed to enable companies to evaluate the value generation of their PSS offerings. In addition, a guideline for PSS design is proposed based on results of this work and field observations. This thesis contributes to a better understanding of PSS adoption in health care by investigating mechanisms in the health care market to understand if PSS can be implemented in a useful manner and how PSS can be adopted in health care in the future. As PSS consists of a number of separate concepts that may be used by themselves and also outside a PSS concept, a detailed analysis was performed to evaluate how PSS concepts are already utilized by industry, as such partial implementations may be a good starting point for full PSS adoption. Adoption of a PSS in any industry requires a measure to evaluate the success of a system implementation or the quality of PSS offerings. Given the complex market network in health care, metrics for evaluations have been identified, linking different dimensions of clinical utility to PSS. Those metrics enable companies to assess PSS systems or scenarios, but also enable development teams to focus their PSS design efforts, as those assessment metrics provide a framework for PSS requirements engineering in this market. Based on the results of the work outlined above, design guidelines were defined to support the development process of PSS in health care.PhD in Manufacturin

Effect of imaging and catheter characteristics on clinical outcome for patients in the PRECISE study

The PRECISE study used convection enhanced delivery (CED) to infuse IL13-PE38QQR in patients with recurrent glioblastoma multiforme (GBM) and compared survival to Gliadel Wafers (GW). The objectives of this retrospective evaluation were to assess: (1) catheter positioning in relation to imaging features and (2) to examine the potential impact of catheter positioning, overall catheter placement and imaging features on long term clinical outcome in the PRECISE study. Catheter positioning and overall catheter placement were scored and used as a surrogate of adequate placement. Imaging studies obtained on day 43 and day 71 after resection were each retrospectively reviewed. Catheter positioning scores, catheter overall placement scores, local tumor control and imaging change scores were reviewed and correlated using Generalized Linear Mixed Models. Cox PH regression analysis was used to examine whether these imaging based variables predicted overall survival (OS) and progression free survival (PFS) after adjusting for age and KPS. Of 180 patients in the CED group, 20 patients did not undergo gross total resection. Of the remaining 160 patients only 53% of patients had fully conforming catheters in respect to overall placement and 51% had adequate catheter positioning scores. Better catheter positioning scores were not correlated with local tumor control (P = 0.61) or imaging change score (P = 0.86). OS and PFS were not correlated with catheter positioning score (OS: P = 0.53; PFS: P = 0.72 respectively), overall placement score (OS: P = 0.55; PFS: P = 0.35) or imaging changes on day 43 MRI (P = 0.88). Catheter positioning scores and overall catheter placement scores were not associated with clinical outcome in this large prospective trial

Shape-fitting concept.

<p>(A) Automated software was used to identify the target (e.g. putamen). (B) The infusion shape was rastered over each pixel to calculate the geometric intersection (white) of the infusion (gray) and target (gray). (B) Resulting coverage map of the putamen for a single 300 <b>µ</b>L infusion.</p

Algorithm implementation in a clinical prototype.

<p>User-friendly implementation in software (iPlan®; Brainlab, Munich) which autosegments the target, autosegments the risk structures and identifies the optimal cannula location to maximize coverage and containment.</p

Development of the infusion model.

<p>(A) The length, width and cannula tip location were measured at each timepoint during the infusion (Vi 10 <b>µ</b>L, 50 <b>µ</b>L, 80 <b>µ</b>L, 120 <b>µ</b>L). (B) The width and tip distances scaled linearly with the infusion length. (C) The distance measures scaled as cubic roots (solid lines) of the infusion volume. (D) The resulting spheroid simulation showed good agreement with the measured volumes.</p

Retrospective validation of shape-fitting model.

<p>The experimental distribution was measured by the Gadolinium enhancement in the T1-weighted FLASH image of a 250 <b>µ</b>L infusion into the oligodendroglioma tumor of a dog, a 50 <b>µ</b>L infusion into the putamen of a non-human primate, and a 150 <b>µ</b>L infusion into the thalamus of a non-human primate. The color overlays show the target (<i>yellow</i>), infusate (<i>red</i>) and their intersection (<i>white</i>). The target coverage (<i>T</i>) and containment (<i>C</i>) are listed above each overlay. All simulated infusions positioned at the experimentally measured cannula location (middle column) showed strong agreement with the experimental distributions (left column), validating the accuracy of the model spheroid shape. Improving the cannula positioning in the putamen and thalamus would have improved the coverage and containment. The distance between the measured and optimized cannula locations was 0.6 mm in the tumor, 5.07 mm in the putamen and 3.2 mm in the thalamus.</p

Prospective application of the shape-fitting algorithm to upcoming human clinical trials.

<p>(A) The 300 <b>µ</b>L and 150 <b>µ</b>L infusions specified in an upcoming Parkinson’s gene therapy trial should be placed as shown to maximize coverage and containment in the post-commissural putamen. (B) The 450 <b>µ</b>L total infusion (vertical dotted line) is predicted to achieve 70% coverage and 67% containment. Increasing the infusion volume would increase the target coverage, but decrease the containment. (C) If the entire putamen were targeted, the infusion would achieve 98% containment but only 47% coverage.</p