Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis

Objective: To quantify the effect of strategies to improve retention in randomised trials.<p></p> Design: Systematic review and meta-analysis.<p></p> Data sources Sources searched: MEDLINE, EMBASE, PsycINFO, DARE, CENTRAL, CINAHL, C2-SPECTR, ERIC, PreMEDLINE, Cochrane Methodology Register, Current Controlled Trials metaRegister, WHO trials platform, Society for Clinical Trials (SCT) conference proceedings and a survey of all UK clinical trial research units.<p></p> Review: methods Included trials were randomised evaluations of strategies to improve retention embedded within host randomised trials. The primary outcome was retention of trial participants. Data from trials were pooled using the fixed-effect model. Subgroup analyses were used to explore the heterogeneity and to determine whether there were any differences in effect by the type of strategy.<p></p> Results: 38 retention trials were identified. Six broad types of strategies were evaluated. Strategies that increased postal questionnaire responses were: adding, that is, giving a monetary incentive (RR 1.18; 95% CI 1.09 to 1.28) and higher valued incentives (RR 1.12; 95% CI 1.04 to 1.22). Offering a monetary incentive, that is, an incentive given on receipt of a completed questionnaire, also increased electronic questionnaire response (RR 1.25; 95% CI 1.14 to 1.38). The evidence for shorter questionnaires (RR 1.04; 95% CI 1.00 to 1.08) and questionnaires relevant to the disease/condition (RR 1.07; 95% CI 1.01 to 1.14) is less clear. On the basis of the results of single trials, the following strategies appeared effective at increasing questionnaire response: recorded delivery of questionnaires (RR 2.08; 95% CI 1.11 to 3.87); a ‘package’ of postal communication strategies (RR 1.43; 95% CI 1.22 to 1.67) and an open trial design (RR 1.37; 95% CI 1.16 to 1.63). There is no good evidence that the following strategies impact on trial response/retention: adding a non-monetary incentive (RR=1.00; 95% CI 0.98 to 1.02); offering a non-monetary incentive (RR=0.99; 95% CI 0.95 to 1.03); ‘enhanced’ letters (RR=1.01; 95% CI 0.97 to 1.05); monetary incentives compared with offering prize draw entry (RR=1.04; 95% CI 0.91 to 1.19); priority postal delivery (RR=1.02; 95% CI 0.95 to 1.09); behavioural motivational strategies (RR=1.08; 95% CI 0.93 to 1.24); additional reminders to participants (RR=1.03; 95% CI 0.99 to 1.06) and questionnaire question order (RR=1.00, 0.97 to 1.02). Also based on single trials, these strategies do not appear effective: a telephone survey compared with a monetary incentive plus questionnaire (RR=1.08; 95% CI 0.94 to 1.24); offering a charity donation (RR=1.02, 95% CI 0.78 to 1.32); sending sites reminders (RR=0.96; 95% CI 0.83 to 1.11); sending questionnaires early (RR=1.10; 95% CI 0.96 to 1.26); longer and clearer questionnaires (RR=1.01, 0.95 to 1.07) and participant case management by trial assistants (RR=1.00; 95% CI 0.97 to 1.04).<p></p> Conclusions: Most of the trials evaluated questionnaire response rather than ways to improve participants return to site for follow-up. Monetary incentives and offers of monetary incentives increase postal and electronic questionnaire response. Some strategies need further evaluation. Application of these results would depend on trial context and follow-up procedures.<p></p&gt

Family caregivers’ conceptualisation of quality end-of-life care for people with dementia: A qualitative study

BACKGROUND: People with dementia have been described as the ‘disadvantaged dying’ with poor end-of-life care. Towards the end of life, people with dementia cannot report on the care they receive. It is therefore important to talk to caregivers; however, few have explored the views about end-of-life care from the caregivers’ perspective. The majority of research on family caregivers has focussed on the burden and psychological impact of caring for a relative with dementia. AIM: This study aimed to explore the views of family caregivers about quality end-of-life care for people with dementia. DESIGN: Qualitative study using in-depth interviews and analysed using thematic analysis. SETTING/PARTICIPANTS: Purposive sampling from a third sector organisation’s caregiver network was used to recruit 47 caregivers in England (2012–2013), consisting of (1) family caregivers of someone who had recently received a diagnosis of dementia, (2) family caregivers currently caring for someone with dementia and (3) bereaved family caregivers. RESULTS: Three over-arching themes were derived from the interviewees’ discourse, including maintaining the person within, fostering respect and dignity and showing compassion and kindness. CONCLUSION: End-of-life care for people with dementia does not differ from care throughout the dementia trajectory. Throughout the findings, there is an implicit underlying theme of conflict: conflict between family caregivers and an increasingly systematised service of care and conflict between family caregivers and professionals. This study has in particular demonstrated the importance of the psycho-social aspects of care, aligning with the holistic definition of palliative care

Identifying additional studies for a systematic review of retention strategies in randomised controlled trials: making contact with trials units and trial methodologists

BACKGROUND: Search strategies for systematic reviews aim to identify all evidence relevant to the research question posed. Reports of methodological research can be difficult to find leading to biased results in systematic reviews of research methodology. Evidence suggests that contact with investigators can help to identify unpublished research. To identify additional eligible randomised controlled trials (RCTs) for a Cochrane systematic review of strategies to improve retention in RCTs, we conducted a survey of UK clinical trials units (CTUs) and made contact with RCT methodologists. METHODS: Key contacts for all UK CTUs were sent a personalised email with a short questionnaire and summary protocol of the Cochrane methodology review. The questionnaire asked whether a RCT evaluating strategies to improve retention embedded in a RCT had ever been conducted by the CTU. Questions about the stage of completion and publication of such RCTs were included. The summary protocol outlined the aims, eligibility criteria, examples of types of retention strategies, and the primary outcome for the systematic review. Personal communication with RCT methodologists and presentations of preliminary results of the review at conferences were also used to identify additional eligible RCTs. We checked the results of our standard searches to see if eligible studies identified through these additional methods were also found using our standard searches. RESULTS: We identified 14 of the 38 RCTs included in the Cochrane methodology review by contacting trials units and methodologists. Eleven of the 14 RCTs identified by these methods were either published in grey literature, in press or unpublished. Three remaining RCTs were fully published at the time. Six of the RCTs identified were not found through any other searches. The RCTs identified represented data for 6 of 14 RCTs of incentive strategies (52% of randomised participants included in the review), and 6 of 14 RCTs of communication strategies (52% of randomised participants included in the Cochrane review). Data were unavailable for two of the RCTs identified. CONCLUSIONS: Methodological evaluations embedded in RCTs may be unpublished, published in the grey literature or where published, poorly indexed in bibliographic databases. To identify such studies and minimise selection bias in systematic reviews of methodological evaluations, reviewers should consider contacting CTUs and trial methodologists

Use of strategies to improve retention in primary care randomised trials: a qualitative study with in-depth interviews

Objective To explore the strategies used to improve retention in primary care randomised trials.<p></p> Design Qualitative in-depth interviews and thematic analysis.<p></p> Participants 29 UK primary care chief and principal investigators, trial managers and research nurses.<p></p> Methods In-depth face-to-face interviews.<p></p> Results Primary care researchers use incentive and communication strategies to improve retention in trials, but were unsure of their effect. Small monetary incentives were used to increase response to postal questionnaires. Non-monetary incentives were used although there was scepticism about the impact of these on retention. Nurses routinely used telephone communication to encourage participants to return for trial follow-up. Trial managers used first class post, shorter questionnaires and improved questionnaire designs with the aim of improving questionnaire response. Interviewees thought an open trial design could lead to biased results and were negative about using behavioural strategies to improve retention. There was consensus among the interviewees that effective communication and rapport with participants, participant altruism, respect for participant's time, flexibility of trial personnel and appointment schedules and trial information improve retention. Interviewees noted particular challenges with retention in mental health trials and those involving teenagers.<p></p> Conclusions The findings of this qualitative study have allowed us to reflect on research practice around retention and highlight a gap between such practice and current evidence. Interviewees describe acting from experience without evidence from the literature, which supports the use of small monetary incentives to improve the questionnaire response. No such evidence exists for non-monetary incentives or first class post, use of which may need reconsideration. An exploration of barriers and facilitators to retention in other research contexts may be justified.<p></p&gt

Prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries: a systematic review and meta-analysis

OBJECTIVE: To systematically review the research conducted on prevalence of frailty and prefrailty among community-dwelling older adults in low-income and middle-income countries (LMICs) and to estimate the pooled prevalence of frailty and prefrailty in community-dwelling older adults in LMICs. DESIGN: Systematic review and meta-analysis. PROSPERO registration number is CRD42016036083. DATA SOURCES: MEDLINE, EMBASE, AMED, Web of Science, CINAHL and WHO Global Health Library were searched from their inception to 12 September 2017. SETTING: Low-income and middle-income countries. PARTICIPANTS: Community-dwelling older adults aged ≥60 years. RESULTS: We screened 7057 citations and 56 studies were included. Forty-seven and 42 studies were included in the frailty and prefrailty meta-analysis, respectively. The majority of studies were from upper middle-income countries. One study was available from low-income countries. The prevalence of frailty varied from 3.9% (China) to 51.4% (Cuba) and prevalence of prefrailty ranged from 13.4% (Tanzania) to 71.6% (Brazil). The pooled prevalence of frailty was 17.4% (95% CI 14.4% to 20.7%, I²=99.2%) and prefrailty was 49.3% (95% CI 46.4% to 52.2%, I²=97.5%). The wide variation in prevalence rates across studies was largely explained by differences in frailty assessment method and the geographic region. These findings are for the studies with a minimum recruitment age 60, 65 and 70 years. CONCLUSION: The prevalence of frailty and prefrailty appears higher in community-dwelling older adults in upper middle-income countries compared with high-income countries, which has important implications for healthcare planning. There is limited evidence on frailty prevalence in lower middle-income and low-income countries

Use of contraceptives and risk of inflammatory bowel disease: A nested case–control study

Background: How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described. // Aim: To examine associations between types of hormonal contraception and development of IBD. // Methods: This was a nested case–control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated. // Results: 4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively). // Conclusions: We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis

Association between frailty and disability among rural community-dwelling older adults in Sri Lanka: a cross-sectional study

OBJECTIVE: We examined the association between frailty and disability in rural community-dwelling older adults in Kegalle district of Sri Lanka. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 746 community-dwelling adults aged ≥60 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Frailty was assessed using the Fried phenotype. Disability was operationalised in terms of having one or more activity limitation/s in instrumental activities of daily living (IADL) and basic activities of daily living (BADL). RESULTS: The median age of the sample was (median 68; IQR 64-75) years and 56.7% were female. 15.2% were frail and 48.5% were prefrail. The prevalence of ≥1 IADL limitations was high, 84.4% among frail adults. 38.7% of frail adults reported ≥1 BADL limitations. Over half of frail older adults (58.3%) reported both ≥1 physical and cognitive IADL limitations. Being frail decreased the odds of having no IADL limitations, and was associated with a higher count of IADL limitations. No significant association was found between prefrailty and number of IADL limitations. CONCLUSIONS: The prevalence of ≥1 IADL limitations was high among rural community-dwelling frail older adults. Findings imply the greater support and care required for rural Sri Lankan frail older adults to live independently in the community

Quality and use of unlicensed vitamin D preparations in primary care in England: retrospective review of national prescription data and laboratory analysis

AIM: To evaluate the type (licensed vs. unlicensed) and cost of preparations used to fulfil vitamin D prescriptions in England over time, and to compare measured vitamin D content of selected vitamin D preparations against labelled claim. METHODS: Retrospective analysis of vitamin D prescription data in primary care in England (2008-2018). Laboratory analysis of 13 selected vitamin D preparations. RESULTS: Alongside a rise in the number of oral licensed colecalciferol preparations from 0 to 27 between 2012 and 2018, the proportion of vitamin D prescriptions in which licensed vitamin D preparations were supplied increased from 11.8 to 54.2%. However, the use of unlicensed food supplements (dose strength: 400-50,000 IU) remained high accounting for 39.7% of vitamin D prescriptions in 2018. The two licensed preparations showed mean (± standard deviation) vitamin D content of 90.9 ± 0.7% and 90.5 ± 3.9% of the labelled claimed amount, meeting the British Pharmacopeia specification for licensed medicines (90-125% of labelled claim). The 11 food supplements showed vitamin D content ranging from 41.2 ± 10.6% to 165.3 ± 17.8% of the labelled claim, with 8 of the preparations failing to comply with the food supplement specification (80-150% of labelled claim). CONCLUSIONS: Despite the increasing availability of quality assured licensed preparations, food supplements continued to be used interchangeably with licensed preparations to fulfil vitamin D prescriptions. Food supplements, manufactured under less stringent quality standards, showed wide variations between measured and declared vitamin D content, which could lead to the risk of under- and over-dosing

Predicting dementia risk in primary care: development and validation of the Dementia Risk Score using routinely collected data

BACKGROUND: Existing dementia risk scores require collection of additional data from patients, limiting their use in practice. Routinely collected healthcare data have the potential to assess dementia risk without the need to collect further information. Our objective was to develop and validate a 5-year dementia risk score derived from primary healthcare data. METHODS: We used data from general practices in The Health Improvement Network (THIN) database from across the UK, randomly selecting 377 practices for a development cohort and identifying 930,395 patients aged 60-95 years without a recording of dementia, cognitive impairment or memory symptoms at baseline. We developed risk algorithm models for two age groups (60-79 and 80-95 years). An external validation was conducted by validating the model on a separate cohort of 264,224 patients from 95 randomly chosen THIN practices that did not contribute to the development cohort. Our main outcome was 5-year risk of first recorded dementia diagnosis. Potential predictors included sociodemographic, cardiovascular, lifestyle and mental health variables. RESULTS: Dementia incidence was 1.88 (95 % CI, 1.83-1.93) and 16.53 (95 % CI, 16.15-16.92) per 1000 PYAR for those aged 60-79 (n = 6017) and 80-95 years (n = 7104), respectively. Predictors for those aged 60-79 included age, sex, social deprivation, smoking, BMI, heavy alcohol use, anti-hypertensive drugs, diabetes, stroke/TIA, atrial fibrillation, aspirin, depression. The discrimination and calibration of the risk algorithm were good for the 60-79 years model; D statistic 2.03 (95 % CI, 1.95-2.11), C index 0.84 (95 % CI, 0.81-0.87), and calibration slope 0.98 (95 % CI, 0.93-1.02). The algorithm had a high negative predictive value, but lower positive predictive value at most risk thresholds. Discrimination and calibration were poor for the 80-95 years model. CONCLUSIONS: Routinely collected data predicts 5-year risk of recorded diagnosis of dementia for those aged 60-79, but not those aged 80+. This algorithm can identify higher risk populations for dementia in primary care. The risk score has a high negative predictive value and may be most helpful in 'ruling out' those at very low risk from further testing or intensive preventative activities