Facilitating the use of the target product profile in academic research: a systematic review.

BACKGROUND: The Target Product Profile (TPP) is a tool used in industry to guide development strategies by addressing user needs and fostering effective communication among stakeholders. However, they are not frequently used in academic research, where they may be equally useful. This systematic review aims to extract the features of accessible TPPs, to identify commonalities and facilitate their integration in academic research methodology. METHODS: We searched peer-reviewed papers published in English developing TPPs for different products and health conditions in four biomedical databases. Interrater agreement, computed on random abstract and paper sets (Cohen's Kappa; percentage agreement with zero tolerance) was > 0.91. We interviewed experts from industry contexts to gain insight on the process of TPP development, and extracted general and specific features on TPP use and structure. RESULTS: 138 papers were eligible for data extraction. Of them, 92% (n = 128) developed a new TPP, with 41.3% (n = 57) focusing on therapeutics. The addressed disease categories were diverse; the largest (47.1%, n = 65) was infectious diseases. Only one TPP was identified for several fields, including global priorities like dementia. Our analyses found that 56.5% of papers (n = 78) was authored by academics, and 57.8% of TPPs (n = 80) featured one threshold level of product performance. The number of TPP features varied widely across and within product types (n = 3-44). Common features included purpose/context of use, shelf life for drug stability and validation aspects. Most papers did not describe the methods used to develop the TPP. We identified aspects to be taken into account to build and report TPPs, as a starting point for more focused initiatives guiding use by academics. DISCUSSION: TPPs are used in academic research mostly for infectious diseases and have heterogeneous features. Our extraction of key features and common structures helps to understand the tool and widen its use in academia. This is of particular relevance for areas of notable unmet needs, like dementia. Collaboration between stakeholders is key for innovation. Tools to streamline communication such as TPPs would support the development of products and services in academia as well as industry.

Returning individual-specific results of a dementia prevalence study: insights from prospective participants living in Switzerland.

OBJECTIVES: To explore prospective participants' preferences regarding the return of their individual-specific results from a dementia prevalence study (a probabilistic diagnosis of dementia). METHODS/DESIGN: We conducted a qualitative study with 22 individuals aged 45 to 86 and resident in the Canton of Ticino (Switzerland). Participants had previously joined the validation phase of an epidemiological study into dementia and its impact. RESULTS: We found that individuals welcome the return of their individual-specific results, provided these meet a number of validity, clinical, and personal utility criteria. They justify researchers' duty to return study findings with the principles of beneficence (eg, providing information that can help participants' medical decision-making) and justice (eg, acknowledging participants' efforts to help research by sharing their personal information). Furthermore, individuals anticipate societal benefits of the return of individual specific study findings, including improved interpersonal relationships among individuals and decreased dementia-related stigma. CONCLUSIONS: Our findings suggest that researchers should address the return of individual-specific study results early on during study design and involve prospective participants in identifying both the conditions under which results should be offered and the perceived individual and societal benefits returning can have.

Estimating the number of people living with dementia at different stages of the condition in India: A Delphi process.

INTRODUCTION: Numerous studies have previously estimated the dementia prevalence in India. However, as these estimates use different methodologies and sampling strategies, generating definitive prevalence estimates can be difficult. METHODS: A Delphi process involving eight clinical and academic experts provided prevalence estimates of dementia within India, split by sex and age. The experts were also asked to estimate the number of people potentially living at different stages of the condition. A priori criteria were used to ascertain the point in which consensus was achieved. RESULTS: Our consensus estimates generated a dementia prevalence of 2.8% (95% CI = 1.9 to 3.6) for those aged 60 years and above in India. Consensus was achieved across age and sex prevalence estimates, with the exception of one (females aged 60-64). Our experts estimated that 42.9% of people living with dementia in India had a mild severity. CONCLUSIONS: The findings indicate that there could be approximately 3.9 million people living with dementia in India, of which 1.7 million could be living with dementia of mild severity. Such estimates can better help researchers and policy makers to estimate the true cost and impact of dementia in India and can inform resource allocation decisions.

Comprehensive measurement of the prevalence of dementia in low- and middle-income countries: STRiDE methodology and its application in Indonesia and South Africa.

BACKGROUND: A core element of the Strengthening Responses to Dementia in Developing Countries (STRiDE) programme was to generate novel data on the prevalence, cost and impact of dementia in low- and middle-income countries, to build better health policy. Indonesia and South Africa are two middle-income countries in need of such data. AIMS: To present the STRiDE methodology and generate estimates of dementia prevalence in Indonesia and South Africa. METHOD: We conducted community-based, single-phase, cross-sectional studies in Indonesia and South Africa, randomly sampling participants aged 65 years or older in each country. Dementia prevalence rates for each country were generated by using the 10/66 short schedule and applying its diagnostic algorithm. Weighted estimates were calculated with national sociodemographic data. RESULTS: Data were collected between September and December 2021 in 2110 people in Indonesia and 408 people in South Africa. The adjusted weighted dementia prevalence was 27.9% (95% CI 25.2-28.9) in Indonesia and 12.5% (95% CI 9.5-16.0) in South Africa. Our results indicate that there could be >4.2 million people in Indonesia and >450 000 people in South Africa who have dementia. Only five participants (0.2%) in Indonesia and two (0.5%) in South Africa had been previously diagnosed with dementia. CONCLUSIONS: Despite prevalence estimates being high, formal diagnosis rates of dementia were very low across both countries (<1%). Further STRiDE investigations will provide indications of the impact and costs of dementia in these countries, but our results provide evidence that dementia needs to be prioritised within national health and social care policy agendas.

Evaluating measurement properties of subjective cognitive decline self-reported outcome measures: a systematic review.

BACKGROUND: Subjective cognitive decline (SCD) is present in the early stage of preclinical Alzheimer's disease (AD) and is associated with an increased risk of further cognitive decline and AD dementia later in life. Early detection of at-risk groups with subjective complaints is critical for targeted dementia prevention at the earliest. Accurate assessment of SCD is crucial. However, current measures lack important psychometric evaluations and or reporting. OBJECTIVES: To systematically evaluate measurement properties of self-reported outcome measures (PROMs) used to assess SCD in the older adult population with or at risk of AD. METHODS AND ANALYSIS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols 2015 Checklist for reporting. We conducted a literature search, screened, and included validation studies of SCD based on self-reported questionnaires from both population-based and clinical studies, conducted in older adults (≥ 55). We critically appraised the included primary studies using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. RESULTS: Sixteen studies met the inclusion criteria. The included studies reported psychometric properties of 17 SCD self-reported questionnaires. We extracted data on the structural validity, internal consistency, test-retest reliability, and cross-cultural validity and found a widespread proneness to bias across studies, and a marked heterogeneity is assessed and reported measurement properties that prevented the consolidation of results. CONCLUSION: Our findings suggest that available SCD questionnaires lack content validity evaluation. Currently available measurements of SCD lack development and validation standards. Further work is needed to develop and validate SCD self-reported measurement with good quality measurement properties.

Investigating the Association Between Polygenic Risk Scores for Alzheimer's Disease With Cognitive Performance and Intrinsic Functional Connectivity in Healthy Adults.

Background: Alzheimer's disease (AD) pathology is present many years before the onset of clinical symptoms. AD dementia cannot be treated. Timely and early detection of people at risk of developing AD is key for primary and secondary prevention. Moreover, understanding the underlying pathology that is present in the earliest stages of AD, and the genetic predisposition to that might contribute to the development of targeted disease-modifying treatments. Objectives: In this study, we aimed to explore whether genetic disposition to AD in asymptomatic individuals is associated with altered intrinsic functional connectivity as well as cognitive performance on neuropsychological tests. Methods: We examined 136 cognitively healthy adults (old group: mean age = 69.32, SD = 4.23; young group: mean age = 31.34, SD = 13.12). All participants had undergone resting-state functional magnetic resonance imagining (fMRI), DNA genotyping to ascertain polygenic risk scores (PRS), and neuropsychological testing for global cognition, working memory, verbal fluency, and executive functions. Results: Two-step hierarchical regression analysis revealed that higher PRS was significantly associated with lower scores in working memory tasks [Letter Number Span: ΔR 2 = 0.077 (p < 0.05); Spatial Span: ΔR 2 = 0.072 (p < 0.05)] in older adults (>60 years). PRS did not show significant modulations of the intrinsic functional connectivity of the posterior cingulate cortex (PCC) with other regions of interest in the brain that are affected in AD. Conclusion: Allele polymorphisms may modify the effect of other AD risk factors. This potential modulation warrants further investigations, particularly in cognitively healthy adults.

Description of the cross-cultural process adopted in the STRiDE (STrengthening Responses to dementia in DEveloping countries) program: A methodological overview.

Cross-cultural adaptation is an important part of using validated questionnaires across countries and settings. Here we describe the cross-cultural process adopted in the STRiDE (STrengthening Responses to dementia in DEveloping countries) program. We adopted a cross-cultural adaptation process including forward translation, back translations, and cognitive interviews of the STRiDE toolkit. In total, 50 older adults and 41 carers across sites in Indonesia and South Africa participated in cognitive interviews; field notes and verbatim quotes are reported. We describe the cross-cultural adaptation process of the STRiDE toolkit. During the process, issues were identified with the translated toolkit, including aspects related to cultural appropriateness, terminology equivalence, and timings. The data demonstrate that a rigorous, yet pragmatic, cross-cultural adaptation process can be achieved even with limited resources. Our process should help the design and conduct of future dementia research in various contexts.

Italian version of the short 10/66 dementia diagnostic schedule: a validation study.

OBJECTIVES: To determine the criterion and concurrent validity of the Italian version of the short 10/66 Dementia Diagnostic Schedule and algorithm in a sample of Italian native speakers, older adults. DESIGN: A cross-sectional, validation study. SETTING: The study was conducted with older adults living in the community and in nursing homes in the Canton of Ticino, Switzerland, and the Piedmont region in Italy between March and August 2019. PARTICIPANTS: A convenience sample of 229 participants (69% females) were recruited. The eligibility criteria were being ≥60 years old and having an informant. The final sample included 74 participants (32%) with a previous clinical diagnosis of dementia and 155 (68%) cognitively healthy older adults. PRIMARY AND SECONDARY OUTCOME MEASURES: The short version of 10/66 Dementia Diagnostic Schedule consists of the Community Screening Instrument for Dementia, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) 10-word list learning task with delayed recall and the depression scale, Euro-Depression (EURO-D) scale. Disability was measured using the WHO Disability Assessment Schedule (WHO-DAS II). RESULTS: The Italian version of the short 10/66 Dementia Diagnostic Schedule showed fair sensitivity (87%), specificity (61%) and agreement with the clinical diagnosis of dementia (kappa=0.40, area under the receiver operating characteristics curve=0.74). Older adults with dementia living in nursing homes had higher disability scores (WHO-DAS II mean=23.14, SE=1.29) than those living in the community (WHO-DAS II mean=7.08, SE=0.66). WHO-DAS II was positively correlated with the short version of the 10/66 dementia diagnosis (ß=5.23, 95% CI 2.05 to 8.41). CONCLUSIONS: In settings where lengthy diagnostic procedures are not feasible, the short 10/66 is a practical tool to identify dementia in older adults. Our findings extend evidence on the validity of the 10/66 dementia diagnostic algorithm to high-income countries, where epidemiological evidence on dementia and its impact is outdated.

Participants' Comprehension of the Informed Consent in an Epidemiological Study on Dementia Prevalence: A Qualitative Study.

Aim: In the absence of an effective treatment, informed participation in dementia research can hardly be underestimated. However, although informed consent is key in biomedical research, it may become a barrier to participation. Whether informed consent may cause confusion and contribute to unfair participant selection in dementia research is not known. In preparation of a future epidemiological study on the prevalence and impact of dementia in Switzerland, we aimed to conduct a qualitative study to explore participants' comprehension of the purpose of informed consent form and process shortly after participation in the pilot and validation study that preceded the large scale survey. Methods: We conducted a qualitative study with 22 participants of the validation phase of an epidemiological study on the prevalence and impact of dementia in Switzerland to capture their understanding of both the nature and the content of the informed consent form and process. Participants were older adults (65 years or more) eligible for a dementia epidemiological study and their informant (a person who could provide information on their health and cognition). None of the participants reported to be suffering from dementia at the time of the interview. Results: We found that participants held inaccurate and potentially trust-threatening beliefs regarding the scope of the informed consent. Participants identified contradictory contextual, formal and content needs that are difficult to be fulfilled, and misperceived the clinical and research settings in terms of informed consent procedures. Conclusions: Participants and their proxies should be informed about both the scope of the informed consent process, and the content of the informed consent document in a focused, age-appropriate manner, while dispelling confusion about the purpose of research.