Valuing Alzheimer's Disease drugs:A health technology assessment perspective on outcomes

ObjectivesDue to the nature of Alzheimer's disease (AD), health technology assessment (HTA) agencies might face considerable challenges in choosing appropriate outcomes and outcome measures for drugs that treat the condition. This study sought to understand which outcomes informed previous HTAs, to explore possible reasons for prioritizations, and derive potential implications for future assessments of AD drugs.MethodWe conducted a literature review of studies that analyzed decisions made in HTAs (across disease areas) in three European countries: England, Germany, and The Netherlands. We then conducted case studies of technology assessments conducted for AD drugs in these countries.ResultsOverall, outcomes measured using clinical scales dominated decisions or recommendations about whether to fund AD drugs, or price negotiations. HTA processes did not always allow the inclusion of outcomes relevant to people with AD, their carers, and families. Processes did not include early discussion and agreement on what would constitute appropriate outcome measures and cut-off points for effects.ConclusionsWe conclude that in order to ensure that future AD drugs are valued appropriately and timely, early agreement with various stakeholders about outcomes, outcome measures, and cut-offs is important

What outcomes are important to patients with mild cognitive impairment or Alzheimer's disease, their caregivers, and health-care professionals? A systematic review

Introduction: Clinical trials involving patients with Alzheimer’s disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.</br

E-epidemiology : Adapting epidemiological methods for the 21st century

The traditional methods in epidemiological data collection are both costly and time consuming and less convenient for longitudinal large-scale studies. During the last decades, epidemiological studies suffer from low response rates, indicating a need to revise methods used in epidemiological data collection. e-epidemiology is the science underlying usage of Information and Communication Technologies (ICT) in epidemiological studies and enable new possibilities for data collection. In this thesis four studies evaluating methods including mobile phones, the web and Interactive Voice Response (IVR) are described. In study I, the feasibility of using an Internet-based hearing test combined with a web-based questionnaire was evaluated in a pilot study among Swedish hunters. The response rate was very low with a bias toward older individuals (40-60 years) who had access to the correct equipment at study start. Though a number of limitations, the hearing-test demonstrates a possibility of using the web in epidemiological data collection. In study II, repeated measures of physical activity level (PAL) through a Java-based questionnaire in mobile phones were compared to a gold standard of measuring energy expenditure. The Java-based physical activity questionnaire sent repeatedly through mobile phones produced average PAL estimates that agreed well with PAL reference values, indicating that the method may be a feasible and cost effective method for data collection on physical activity. Study III compared data collected through Short Message Service (SMS) to traditional telephone interviews in a population-based sample. Though the study produced very low response rate, the results on influenza vaccination status was not statistically significantly different from data collected through telephone interviews. Study IV compared data on self-reports on infectious disease where the participants could choose between web and IVR. The web was more popular than IVR and attracted more men and younger individuals with a higher completed education compared to IVR. There was no statistically significantly difference of reported infections or Influenza-Like Illness (ILI) between the two techniques after adjusting for available confounders. Studies I, III and IV were affected by low response rates, effecting both the validity and precision of the results. All studies were affected by bias and all but study II were probably confounded by age. The mechanisms behind these factors are important to evaluate further in order to understand how it affects the collected data. However, when possible to adjust for confounders, the techniques per se did not seem to influence data negatively compared to reference data. All studies were evaluated on a Swedish population with high access to the Internet and mobile phones, and the results might not be generalizable to populations with less access. This thesis has demonstrated a fraction of the possibilities using ICT in epidemiological data collection and e-epidemiology is still in its youth. Once the techniques have been thoroughly evaluated, there are probably endless possibilities to ensure high quality data collection through methods adapted to a modern society

Estimation of Physical Activity Levels Using Cell Phone Questionnaires: A Comparison With Accelerometry for Evaluation of Between-Subject and Within-Subject Variations

Background: Physical activity promotes health and longevity. Further elaboration of the role of physical activity for human health in epidemiological studies on large samples requires accurate methods that are easy to use, cheap, and possible to repeat. The use of telecommunication technologies such as cell phones is highly interesting in this respect. In an earlier report, we showed that physical activity level (PAL) assessed using a cell phone procedure agreed well with corresponding estimates obtained using the doubly labeled water method. However, our earlier study indicated high within-subject variation in relation to between-subject variations in PAL using cell phones, but we could not assess if this was a true variation of PAL or an artifact of the cell phone technique. less thanbrgreater than less thanbrgreater thanObjective: Our objective was to compare within-and between-subject variations in PAL by means of cell phones with corresponding estimates using an accelerometer. In addition, we compared the agreement of daily PAL values obtained using the cell phone questionnaire with corresponding data obtained using an accelerometer. less thanbrgreater than less thanbrgreater thanMethods: PAL was measured both with the cell phone questionnaire and with a triaxial accelerometer daily during a 2-week study period in 21 healthy Swedish women (20 to 45 years of age and BMI from 17.7 kg/m(2) to 33.6 kg/m(2)). The results were evaluated by fitting linear mixed effect models and descriptive statistics and graphs. less thanbrgreater than less thanbrgreater thanResults: With the accelerometer, 57% (95% confidence interval [CI] 40%-66%) of the variation was within subjects, while with the cell phone, within-subject variation was 76% (95% CI 59%-83%). The day-to-day variations in PAL observed using the cell phone questions agreed well with the corresponding accelerometer results. less thanbrgreater than less thanbrgreater thanConclusions: Both the cell phone questionnaire and the accelerometer showed high within-subject variations. Furthermore, day-to-day variations in PAL within subjects assessed using the cell phone agreed well with corresponding accelerometer values. Consequently, our cell phone questionnaire is a promising tool for assessing levels of physical activity. The tool may be useful for large-scale prospective studies.Funding Agencies|Swedish Research Council, FORMAS||Magnus Bergvall Foundation||Thuring Foundation||Swedish Society of Medicine|

The Validity of Self-Initiated, Event-Driven Infectious Disease Reporting in General Population Cohorts

<div><p>Background</p><p>The 2009/2010 pandemic influenza highlighted the need for valid and timely incidence data. In 2007 we started the development of a passive surveillance scheme based on passive follow-up of representative general population cohorts. Cohort members are asked to spontaneously report all instances of colds and fevers as soon as they occur for up to 9 months. Suspecting that compliance might be poor, we aimed to assess the validity of self-initiated, event-driven outcome reporting over long periods.</p><p>Methods</p><p>During two 8 week periods in 2008 and 2009, 2376 and 2514 cohort members in Stockholm County were sent one-week recall questionnaires, which served as reference method.</p><p>Results</p><p>The questionnaires were completed by 88% and 86% of the cohort members. Whilst the false positive proportion (1–specificity) in the reporting was low (upper bound of the 95% confidence interval [CI] ≤2% in each season), the false negative proportion (failure to report, 1–sensitivity) was considerable (60% [95% CI 52%–67%] in each season). Still, the resulting epidemic curves for influenza-like illness compared well with those from existing General Practitioner-based sentinel surveillance in terms of shape, timing of peak, and year-to-year variation. This suggested that the error was fairly constant.</p><p>Conclusions</p><p>Passive long-term surveillance through self-initiated, event-driven outcome reporting underestimates incidence rates of common upper respiratory tract infections. However, because underreporting appears predictable, simple corrections could potentially restore validity.</p></div

Epidemic curves for influenza-like illness (ILI).

<p>The curves are derived from the passive follow-up with self-initiated, event-driven outcome reporting in population-based surveillance cohorts (solid line) and adjusted for imperfect sensitivity (dashed line). The upper graph represents 2008, the lower one 2009.</p

Number of persons by number of illness episodes in the end-of-follow-up questionnaire and number of event-driven surveillance reports during the entire 2007/2008 season.

<p>Wilcoxon matched pairs signed rank sum test p<0.0001.</p