The Importance of Economic Perspective and Quantitative Approaches in Oncology Value Frameworks of Drug Selection and Shared Decision Making

The debate around value in oncology drug selection has been prominent in recent years, and several professional bodies have furthered this debate by advocating for so-called value frameworks. Herein, we provide a viewpoint on these value frameworks, emphasizing the need to consider 4 key aspects: (1) the economic underpinnings of value; (2) the importance of the perspective adopted in the valuation; (3) the importance of the difference between absolute and relative measures of risk and measuring patient preferences; and (4) the recognition of multiple quality-of-life (QoL) domains, and the aggregation and valuation of those domains, through utilities within a multicriteria decision analysis, may allow prioritization of QoL above the tallying of safety events, particularly in a value framework focusing on the individual patient. While several frameworks exist, they incorporate different attributes and—importantly—assess value from alternative perspectives, including those of patients, regulators, payers, and society. The various perspectives necessarily lead to potentially different, if not sometimes divergent, conclusions about the valuation. We show that the perspective of the valuation affects the framing of the risk/benefit question and the methodology to measure the individual patient choice, or preference, as opposed to the collective, or population, choice. We focus specifically on the American Society of Clinical Oncology (ASCO) Value Framework. We argue that its laudable intent to assist in shared clinician-patient decision making can be augmented by more formally adopting methodology underpinned by micro- and health economic concepts, as well as application of formal quantitative approaches. Our recommendations for value frameworks focusing on the individual patient, such as the ASCO Value Framework, are 3-fold: (1) ensure that stakeholders understand the importance of the adopted (economic) perspective; (2) consider using exclusively absolute measures of risk and formal patientpreference methodology; and (3) consider foregoing safety parameters for higher-order utility considerations

Cost-effectiveness of DNA-diagnosis for four monogenic diseases

In this paper the costs and benefits associated with DNA-diagnosis of individuals who are at risk of a child with a monogenic disease and who seek genetic counselling because of their reproductive plans are predicted under various assumptions using a mathematical model. Four monogenic diseases have been considered: cystic fibrosis, Duchenne muscular dystrophy, myotonic dystrophy and fragile X syndrome. Counselling (triggered by prior information) on the basis of DNA-diagnosis is compared to the situation that only risk evaluation based on pedigree analysis is possible. The results show for each disease that with DNA-diagnosis couples can be more confident in choosing (further) offspring leading to the birth of more healthy children while the number of affected children is reduced. The costs minus savings within the health care sector depend on the prior risks and to the future burden of the monogenic illness considered. DNA-diagnosis of relative "low" prior risks of a child with CF (e.g. 1:180, 1:240 and 1:480) leads to costs in stead of savings. For higher prior risks of CF and for the three other diseases DNA-diagnosis induces considerable savings. This result remains valid when assumptions regarding behaviour regarding reproduction and receiving DNA-diagnosis under different circumstances are varied

Osteoporosis in the Netherlands; A burden of illness study commissioned by Merck Sharp & Dohme

This report provides an overview of the available quantitative information about osteoporosis in the Netherlands, and of the costs associated with it. We present information relevant for this country, making as few assumptions as possible. Although the main subject is osteoporosis, the focus in this report is on fractures, as these are the most relevant outcome events of this condition. Data were collected from publicly available data sources and from international literature and information is mostly about the year 1993. The reader finds detailed information about the occurrence of osteoporosis and fractures, the utilization of health care, mortality, and the costs in the results section of this report. In the conclusions, we present a synthesis of the most important findings. Osteoporosis is, by consensus, defined as a systemic skeletal disease, characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. There is an important age-related decrease in bone mass and bone strength. Osteoporosis is primarily described in post-menopausal women but men are not free from it; they also reach high fracture incidence rates at an older age. Combined with the longer survival of women, this leads to the observation that most osteoporotic fractures are encountered in females. Osteoporosis and fractures are a major source of illness and healthcare costs in the Netherlands, both today as in the foreseeable future. Especially the most serious consequence, hip fracture, is frequent and the incidence is increasing. The total number of hip fractures will inevitable rise if no serious prevention efforts are undertaken. For the prevention of osteoporotic fractures it is important to know who are at risk as well as which preventive strategy is effective for the different risk categories. The parameter that is most commonly used nowadays to determine fracture risk is bone mineral density (BMD), but also other factors are important contributors to the fracture risk, namely the previously mentioned bone quality and the propensity to fall. Prevention only focussed on bone mineral density will thus do nothing to prevent the hip fractures caused by the above mentioned factors. An additional effect of therapy on bone quality can be important and the intervention should certainly not have adverse effects on bone quality. Reducing the frequency and severity of falls, and the use of external protective devices, together with physical exercise and other lifestyle interventions, have been looked at as additional intervention possibilities. Patients with a hip fracture more often have concomitant illnesses and a poor general condition. This condition in itself can increase the risk of falling and the perioperative risk. This situation can also impair the rehabilitation after treatment and hamper mobilization. Osteoporosis and fractures are found to be an important cause of health care consumption. Hip fractures lead to long hospita

Becoming deafblind: Negotiating a place in a hostile world

Doctor of PhilosophyThis study addresses the situation of adults who become deafblind. To date, their everday lives have received little attention in the research literature. Of the few studies conducted many involve surveys, the findings of which present the characteristics of people who are deafblind such as their rates of employment, need for support, or use of equipment. There are also a small number of qualitative studies that have explored the effects of having dual sensory impairment, and particularly in relation to communication and psycho-social wellbeing. Important as these research efforts have been, there is little empirical information available about the everyday lives of people who become deafblind and their concerns, nor any systematic attempt to theorise their experiences. There are however many personal anecdotes typically presented at conferences or through community publications and newsletters. This project aimed to redress the gap in the literature by developing a theoretical framework to explain the everyday experiences of adult who become deafblind. In doing so, it built upon the research and anecdotal literature with an overall purpose of presenting, through rigorous research, the experiences of adults who become deafblind and to do so within the broader discourse on disability and disablism. The study was informed by the social relational understanding of disability developed within the Nordic countries. Grounded theory was the method of choice to examine the lives of adults who become deafblind from their own perspective.Participant observation was employed through direct engagement in shared experiences with adults who have become deafblind both at a social group and via an e-mail list group. Mulitple in-depth interviews were undertaken both face to face and by e-mail with a smaller group of eight participants.The core finding from this study is that people who become deafblind are rendered interactionally powerless in a society predicated on seeing and hearing. The powerlessness that they experience comes from having this dual impairment in a world in which being able to see and hear are expected both in the physical and social environment. The inability of people who become deafblind to 'know and be' in the world in the same way as others results in them feeling, and experienceing, interactional powerlessness. In response, people who become deafblind actively engage in trying to minimise or remove their powerlessness. They do so by working to negotiate a place in this hostile world. They adopt four interrelated strategies, namely, doing things differently, managing support relationships, survivings others' perceptions and presenting sides of self.This study, with its central tenet that interactional powerlessness drives ongoing attempts to negotiate a place makes a theoretical contribution to understanding the experience of becoming deafblind. The findings support the concept of disbaility as social relational. Disability is not the same as the sensory impairment, rather it is expressed in the organisation of personal relations in society which render some more powerful than others and in this case, some less powerful due to their inability to use the natural means of communication of hearing and sight. Moreover, the study findings propose that professionals working with people with this dual sensory impairment must endeavour to reduce their part in the hostile world by providing information about options and support available; recognising the complexity of these adults support requirements; and considering the link between psycho-emotional issues and disablism. Further research is needed to understand empirically and theoretically the relative contribution of personal relationships vis a vis organisational or structural relationships in disabling people who become deafblind

An exploration of the non-iterative time trade off method to value health states

Time Trade-Off (TTO) usually relies on “iteration”, which is susceptible to bias. Discrete Choice Experiment with duration (or DCETTO) is free of such bias, but respondents find this cognitively more challenging. This paper explores non-iterative TTO with or without lead time: NI(LT)TTO. In NI(LT)TTO respondents see a series of independent pairwise choices without iteration (similar to DCETTO), but one of the two scenarios always involves full health for a shorter duration (similar to TTO). We compare three different “Types” of NI(LT)TTO relative to DCETTO. Each Type is presented in two “Modes”: (a) verbally tabulated (as in a DCE); and (b) with visual aids (as in a TTO). The study has eight survey variants, each with 12 experimental choice tasks and a 13th task with a logically determined answer. Data on the 12 experimental choices from an online survey of 6,618 respondents are modelled, by variant, using conditional logistic regressions. The results indicate that NI(LT)TTO is feasible, but some relatively mild states appear to have implausibly low predicted values, and the range of predicted values is much narrower than in DCETTO. The presentation of NI(LT)TTO tasks needs further improvement

One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the addit

An innovative approach to modelling the optimal treatment sequence for patients with relapsing–remitting multiple sclerosis : implementation, validation, and impact of the decision-making approach

Introduction An innovative computational model was developed to address challenges regarding the evaluation of treatment sequences in patients with relapsing–remitting multiple sclerosis (RRMS) through the concept of a ‘virtual’ physician who observes and assesses patients over time. We describe the implementation and validation of the model, then apply this framework as a case study to determine the impact of different decision-making approaches on the optimal sequence of disease-modifying therapies (DMTs) and associated outcomes. Methods A patient-level discrete event simulation (DES) was used to model heterogeneity in disease trajectories and outcomes. The evaluation of DMT options was implemented through a Markov model representing the patient’s disease; outcomes included lifetime costs and quality of life. The DES and Markov models underwent internal and external validation. Analyses of the optimal treatment sequence for each patient were based on several decision-making criteria. These treatment sequences were compared to current treatment guidelines. Results Internal validation indicated that model outcomes for natural history were consistent with the input parameters used to inform the model. Costs and quality of life outcomes were successfully validated against published reference models. Whereas each decision-making criterion generated a different optimal treatment sequence, cladribine tablets were the only DMT common to all treatment sequences. By choosing treatments on the basis of minimising disease progression or number of relapses, it was possible to improve on current treatment guidelines; however, these treatment sequences were more costly. Maximising cost-effectiveness resulted in the lowest costs but was also associated with the worst outcomes. Conclusions The model was robust in generating outcomes consistent with published models and studies. It was also able to identify optimal treatment sequences based on different decision criteria. This innovative modelling framework has the potential to simulate individual patient trajectories in the current treatment landscape and may be useful for treatment switching and treatment positioning decisions in RRMS

Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be$2,973 per patient. CONCLUSION: As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization