Conducting public involvement in dementia research: The contribution of the European Working Group of People with Dementia to the ROADMAP project.

BACKGROUND: Dementia outcomes include memory loss, language impairment, reduced quality of life and personality changes. Research suggests that outcomes selected for dementia clinical trials might not be the most important to people affected. OBJECTIVE: One of the goals of the 'Real world Outcomes across the Alzheimer's Disease spectrum for better care: Multi-modal data Access Platform' (ROADMAP) project was to identify important outcomes from the perspective of people with dementia and their caregivers. We review how ROADMAP's Public Involvement shaped the programme, impacted the research process and gave voice to people affected by dementia. DESIGN: The European Working Group of People with Dementia (EWGPWD) were invited to participate. In-person consultations were held with people with dementia and caregivers, with advance information provided on ROADMAP activities. Constructive criticism of survey content, layout and accessibility was sought, as were views and perspectives on terminology and key concepts around disease progression. RESULTS: The working group provided significant improvements to survey accessibility and acceptability. They promoted better understanding of concepts around disease progression and how researchers might approach measuring and interpreting findings. They effectively expressed difficult concepts through real-world examples. CONCLUSIONS: The role of the EWGPWD in ROADMAP was crucial, and its impact was highly influential. Involvement from the design stage helped shape the ethos of the programme and ultimately its meaningfulness. PUBLIC CONTRIBUTION: People with dementia and their carers were involved through structured consultations and invited to provide feedback on project materials, methods and insight into terminology and relevant concepts.

Valuing Alzheimer's disease drugs: a health technology assessment perspective on outcomes.

OBJECTIVES: Due 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. METHOD: We 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. RESULTS: Overall, 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. CONCLUSIONS: We 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.

Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube.

INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.

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.

Challenges for Optimizing Real-World Evidence in Alzheimer's Disease: The ROADMAP Project.

ROADMAP is a public-private advisory partnership to evaluate the usability of multiple data sources, including real-world evidence, in the decision-making process for new treatments in Alzheimer's disease, and to advance key concepts in disease and pharmacoeconomic modeling. ROADMAP identified key disease and patient outcomes for stakeholders to make informed funding and treatment decisions, provided advice on data integration methods and standards, and developed conceptual cost-effectiveness and disease models designed in part to assess whether early treatment provides long-term benefit.

The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer.

This systematic review aims to improve understanding of the burden of disease associated with brain metastases from non-small-cell lung cancer (NSCLC) in terms of survival, quality of life (QoL) and economic impact. PubMed/MEDLINE, Cochrane collaboration and EMBASE databases were searched for articles published in English from 2000 to 2014. Of 3288 abstracts retrieved, 3156 were eliminated without a full-text review. Of the 132 articles that received a full-text review, a final set of 93 articles was included in an initial literature analysis. In order to homogenize the patient populations evaluated, we included entries that were either entirely composed of NSCLC patients or that had >50% of NSCLC patients in the total study population. From the studies identified in this systematic review, median OS and PFS varied based on the type of treatment received, although whole-brain radiotherapy (WBRT) was associated with the shortest OS and PFS durations. Regimens incorporating targeted therapy in molecularly selected patients were associated with the longest OS and PFS durations. QoL findings varied among studies, generally WBRT resulted in stable or worsening QoL scores rather than improvements. Healthcare costs were increased following diagnosis of brain metastases regardless of treatment. The findings from this review highlight the need for more effective treatments of brain metastases from NSCLC that improve survival function, QoL and potentially decrease costs.

Annual Medical Costs of Swedish Patients with Type 2 Diabetes Before and After Insulin Initiation.

INTRODUCTION: Although insulin is one of the most effective interventions for the treatment of type 2 diabetes, its disadvantages incur substantial medical cost. This study was designed to evaluate the medical costs of Swedish type 2 diabetic patients initiating insulin on top of metformin and/or sulfonylurea (SU), and to evaluate if costs before and after insulin initiation differ for patients where insulin is initiated above or below the recommended glycosylated hemoglobin (HbA1c) level (7.5%). METHODS: This was a register-based retrospective cohort study in which patients were identified from the Sörmland county council diabetes register. Patients being prescribed at least one prescription of metformin and/or SU from 2003 to 2010, and later prescribed insulin, were included. RESULTS: One hundred patients fulfilled the inclusion criteria and had at least 1 year of follow-up. The mean age was 61 years and 59% of patients were male. Mean time since diagnosis was 4.1 years, and since initiation of insulin was 2.2 years. The mean HbA1c level at index date was 8.0%. Total mean costs for the whole cohort were SEK 17,230 [standard deviation (SD) 17,228] the year before insulin initiation, and SEK 31,656 (SD 24,331) the year after insulin initiation (p < 0.0001). When stratifying by HbA1c level, patients with HbA1c <7.5% had total healthcare costs of SEK 17,678 (SD 12,946) the year before the index date and SEK 35,747 (SD 30,411) the year after (p < 0.0001). Patients with HbA1c levels ≥7.5% had total healthcare costs of SEK 16,918 (SD 19,769) the year before the index date and SEK 28,813 (SD 18,779) the year after (p < 0.0001). CONCLUSION: Despite the small sample size, this study demonstrates that mean annual medical costs almost double the year after patients are initiated on insulin. The costs increased the year after insulin initiation, regardless of the HbA1c level at initiation of insulin, and the largest increase in costs were due to increased filled prescriptions.

The validity of self-initiated, event-driven infectious disease reporting in general population cohorts.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Estimating physical activity using a cell phone questionnaire sent by means of short message service (SMS): a randomized population-based study.

An investigation in a randomized population-based Swedish study with 564 participants aged 18-80 years showed that mean physical activity levels obtained using short message service (SMS) by means of cell phones (n = 171) were equal to corresponding levels obtained when sending identical questions by web (n = 182) or paper (n = 211). The response rates were similar for the SMS, web and paper groups.

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. OBJECTIVE: 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. METHODS: 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/m² to 33.6 kg/m²). The results were evaluated by fitting linear mixed effect models and descriptive statistics and graphs. RESULTS: 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. CONCLUSIONS: 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.

Interactive voice response and web-based questionnaires for population-based infectious disease reporting.

The authors aimed to evaluate the web and an Interactive Voice Response (IVR) phone service as vehicles in population-based infectious disease surveillance. Fourteen thousand subjects were randomly selected from the Swedish population register and asked to prospectively report all respiratory tract infections, including Influenza-like Illness (ILI-clinical symptoms indicative of influenza but no laboratory confirmation), immediately as they occurred during a 36-week period starting October 2007. Participants were classified as belonging to the web or IVR group based on their choice of technology for initial registration. In all, 1,297 individuals registered via IVR while 2,044 chose the web. The latter were more often young and well-educated than those registered via IVR. Overall, 52% of the participants reported at least one infection episode. The risk of an infectious disease report was 14% (95% CI: 6, 22%) higher in the web group than in the IVR group. For ILI the excess was 27% (95% CI: 11, 47%). After adjustments for socio-demographic factors, statistically non-significant excesses of 1 and 8% remained, indicating trivial differences potentially attributable to the two reporting techniques. With attention to confounding, it should be possible to combine the web and IVR for simple reporting of infectious disease symptoms.

An internet-based hearing test for simple audiometry in nonclinical settings: preliminary validation and proof of principle.

OBJECTIVE: To investigate the validity and reproducibility of a newly developed internet-based self-administered hearing test using clinical pure-tone air-conducted audiometry as gold standard. STUDY DESIGN: Cross-sectional intrasubject comparative study. SETTING: Karolinska University Hospital, Solna, Sweden. PATIENTS: Seventy-two participants (79% women) with mean age of 45 years (range, 19-71 yr). Twenty participants had impaired hearing according to the gold standard test. INTERVENTIONS: Hearing tests. MAIN OUTCOME MEASURES: The Pearson correlation coefficient between the results of the studied Internet-based hearing test and the gold standard test, the greatest mean differences in decibel between the 2 tests over tested frequencies, sensitivity and specificity to diagnose hearing loss defined by Heibel-Lidén, and test-retest reproducibility with the Pearson correlation coefficient. RESULTS: The Pearson correlation coefficient was 0.94 (p < 0.0001) for the right ear and 0.93 for the left (p = 0.0001). The greatest mean differences were seen for the frequencies 2 and 4 kHz, with -5.6 dB (standard deviation, 8.29), and -5.1 dB (standard deviation, 6.9), respectively. The 75th percentiles of intraindividual test-gold standard differences did not exceed -10 dB for any of the frequencies. The sensitivity for hearing loss was 75% (95% confidence interval, 51%-90%), and the specificity was 96% (95% confidence interval, 86%-99%). The test-retest reproducibility was excellent, with a Pearson correlation coefficient of 0.99 (p < 0.0001) for both ears. CONCLUSION: It is possible to assess hearing with reasonable accuracy using an Internet-based hearing test on a personal computer with headphones. The practical viability of self-administration in participants' homes needs further evaluation.

Measures of physical activity using cell phones: validation using criterion methods.

BACKGROUND: Physical activity is associated with reduced risks of many chronic diseases. Data collected on physical activity in large epidemiological studies is often based on paper questionnaires. The validity of these questionnaires is debated, and more effective methods are needed. OBJECTIVE: This study evaluates repeated measures of physical activity level (PAL) and the feasibility of using a Java-based questionnaire downloaded onto cell phones for collection of such data. The data obtained were compared with reference estimates based on the doubly labeled water method and indirect calorimetry (PAL(ref)). METHOD: Using a Java-based cell phone application, 22 women reported their physical activity based on two short questions answered daily over a 14-day period (PAL(cell)). Results were compared with reference data obtained from the doubly labeled water method and indirect calorimetry (PAL(ref)). Results were also compared against physical activity levels assessed by two regular paper questionnaires completed by women at the end of the 14-day period (PAL(quest1) and PAL(quest2)). PAL(cell), PAL(quest1), and PAL(quest2) were compared with PAL(ref) using the Bland and Altman procedure. RESULTS: The mean difference between PAL(cell) and PAL(ref) was small (0.014) with narrow limits of agreement (2SD = 0.30). Compared with PAL(ref), the mean difference was also small for PAL(quest1) and PAL(quest2) (0.004 and 0.07, respectively); however, the limits of agreement were wider (PAL(quest1), 2SD = 0.50 and PAL(quest2), 2SD = 0.90). The test for trend was statistically significant for PAL(quest1) (slope of regression line = 0.79, P = .04) as well as for PAL(quest2) (slope of regression line = 1.58, P < .001) when compared with PAL(ref). CONCLUSION: A Java-based physical activity questionnaire administered daily using cell phones produced PAL estimates that agreed well with PAL reference values. Furthermore, the limits of agreement between PAL obtained using cell phones, and reference values were narrower than for corresponding estimates obtained using paper questionnaires. Java-based questionnaires downloaded onto cell phones may be a feasible and cost-effective method of data collection for large-scale prospective studies of physical activity.

SMS versus telephone interviews for epidemiological data collection: feasibility study estimating influenza vaccination coverage in the Swedish population.

This study compared the use of Short Message Service (SMS) on mobile phones and the use of telephone interviews in collecting self-reported data about influenza vaccination. Through random selection from the Swedish population registry, 2,400 individuals were assigned to be contacted through SMS (SMS-group), and 2,150 were assigned to undergo personal telephone interviews (TI-group). Both groups were asked three questions about influenza and influenza vaccination. Mobile phone numbers were found for 1,055 persons in the SMS-group of whom 154 (6% of the original sample; 15% of all who had a listed mobile phone number) responded. Landline or mobile phone numbers were found for 1,636 persons in the TI-group and 1,009 (47% of the original TI sample; 62% of those where a telephone number was found) responded. The vaccination data collected via SMS was not statistically significantly different from data collected through telephone interviews, and adjustment for different background factors did not change this. Compared to the original sample, there was an under representation of elderly and less educated individuals among the participants in the SMS-group, and under representation of less educated in the TI-group. Though the participation rate was low, SMS is a feasible method for collection of information on vaccination status data among the Swedish population compared to telephone interviews.

Evaluation of an internet-based hearing test--comparison with established methods for detection of hearing loss.

BACKGROUND: Hearing impairment is most accurately measured by a clinical pure-tone audiogram. This method is not suitable for large-scale, population-based epidemiological studies as it requires that study participants visit a clinic with trained personnel. An alternative approach to measuring hearing ability is self-estimation through questionnaires, but the correlation to clinical audiometric tests varies. OBJECTIVE: To evaluate an Internet-based hearing test pilot compared to a question about self-estimated hearing and the feasibility of using an Internet-based hearing test and an Internet-based questionnaire in a population of 560 members of the Swedish Hunters' Association in the age group 20-60 years. METHODS: An invitation was mailed to the participants in March 2007 together with the URL to the study Web site, a personal username, and a password. The Web site included the questionnaire, the hearing test, and instructions for participating in the study. The hearing test resembles a clinical audiogram presenting 6 tones between 500 and 8000 Hz. Tones are presented between 0 and 60 dB, and the participant responds to the tones by pressing the space bar. The hearing test requires headphones and is based on JAVA programming. Before the participant can start the hearing test, it has to be calibrated against a reference person with good hearing between 15 and 35 years of age. RESULTS: After 5 months, 162 out of 560 (29%) had answered the questionnaire, out of which 88 (16%) had completed the hearing test. Those who actively declined participation numbered 230 out of 560 (41%). After removing duplicates and hearing tests calibrated by unreliable reference data, 61 hearing tests remained for analysis. The prevalence of hearing impairment from the Internet-based hearing test was 20% (12 out of 61), compared to 52% (32 out of 61) from the self-estimated question. Those who completed the hearing test were older than the non-participants, and more had headphones (P = .003) and the correct version of the JAVA program (P = .007) than those who only answered the questionnaire. CONCLUSIONS: Though an Internet-based hearing test cannot replace a clinical pure-tone audiogram conducted by a trained audiologist, it is a valid and useful screening tool for hearing ability in a large population carried out at a low cost.

Will forensic use of medical biobanks decrease public trust in healthcare services? Some empirical observations.

AIM: The authors tested the prevalent hypothesis that forensic use of medical biobanks has a negative impact on public trust in healthcare services. METHOD: A questionnaire was sent to 1,184 inhabitant in the age group 20-80 years in Stockholm County, Sweden, in November 2005. RESULTS: With a response rate of 68.4%, the results showed that a majority (88.1%) of the respondents thought that it would be acceptable for the police to gain access to genetic samples stored in relation to healthcare; 5.6% said no and 6.3% were uncertain. In the case of police access to medical biobanks, a minority (6.3%) indicated that this would have a negative impact on their trust, a larger proportion (37.8%) that it would influence their trust in the healthcare services positively, and 56% stated that it would not affect their trust at all. CONCLUSION: The hypothesis tested appears to be unfounded. This should cause us to reconsider prevalent assumptions and current policies on the interface of medical and forensic genetics.