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Frank Sullivan

Publications and source records attributed to Frank Sullivan.

At least 19 recordsLinked to original sources
PubMed2026

Strategies to improve recruitment to randomised trials.

BACKGROUND: Recruiting participants to randomised controlled trials (RCTs) is challenging. Identifying effective recruitment strategies would benefit health research: poor recruitment leads to underpowered trials, reducing the reliability of findings and increasing the risk of wasted resources, ethical concerns, and trial failure. Evidence to inform recruitment strategies is increasingly generated through Studies Within A Trial (SWATs), which are methodological studies embedded within host RCTs. This is an update of a review last published in 2018. OBJECTIVES: Primary: to quantify the effects of strategies to improve recruitment of participants to RCTs. Secondary: to evaluate recruitment strategies' cost-effectiveness and impact on retention, and the equity, diversity, and inclusion (EDI) characteristics of recruited participants. SEARCH METHODS: We used MEDLINE, Embase, and six other databases to identify the studies included in the review. We also sought unpublished recruitment SWATs through social media and targeted email dissemination to trial methodology networks. The latest search date was 16 February 2023. SELECTION CRITERIA: We included randomised SWATs evaluating trial recruitment strategies embedded in healthcare and non-healthcare trials. We excluded quasi-randomised, hypothetical, questionnaire-only, retention-only, or clinician incentive studies. DATA COLLECTION AND ANALYSIS: Primary outcome: proportion of eligible participants or centres recruited. SECONDARY OUTCOMES: cost-effectiveness, retention rates, and EDI characteristics of included participants. We conducted random-effects meta-analysis for strategies evaluated in at least two studies; otherwise, we synthesised results narratively. We reported effects as risk differences (RDs) with 95% confidence intervals (CIs), and assessed between-trial heterogeneity. We used GRADE to assess the certainty of evidence for the primary outcome. We expressed cost-effectiveness as the incremental cost per additional participant recruited in pounds sterling (GBP). MAIN RESULTS: We identified 91 eligible studies (53 new to this update), providing 94 comparisons and involving at least 176,747 participants. Eighty-one studies involved strategies aimed at trial participants, while 10 evaluated strategies aimed at recruiters. All were healthcare studies. We found 65 recruitment strategies; 49 were evaluated in a single study. Only five strategies were supported by high-certainty evidence according to GRADE criteria, and we focus on these strategies in the summary below. Open-label trials versus blinded, placebo trials. Open-label trials recruited more participants than blinded trials (RD 10%, 95% CI 8% to 12%; 3 studies, 9004 participants), corresponding to approximately 10 additional participants per 100 approached. The studies involved mostly women in the UK and Estonia. No cost or retention data were reported. Telephone reminder versus no telephone reminder. Telephone reminders to people who did not respond to an initial postal invitation boosted recruitment by 6% (95% CI 3% to 9%; 2 studies, 1450 participants), in trials with low underlying recruitment (we are less certain for trials with over 10% recruitment). The studies involved people with a mean age of 58 years in Canada and Norway. No cost or retention data were reported. Recruitment primer letter versus no letter. Pre-recruitment letters and leaflets designed to encourage participation made little or no difference to recruitment (absolute improvement 1%, 95% CI -1% to 2%; 2 studies, 5376 participants), and were associated with increased costs compared to not sending a primer (incremental cost: GBP 2.08). The studies involved mostly older white people in the UK and Ireland. Multimedia information via a digital link/QR code plus paper participant information leaflet (PIL) versus paper PIL alone. This made little or no difference to recruitment (absolute improvement 0%, 95% CI -1% to 1%; 7 studies, 11,612 participants) and retention (absolute improvement 0%, 95% CI -2% to 3%; 5 studies, 7403 participants), and increased costs compared to not including multimedia information (incremental cost: GBP 0.78). The studies involved people in the UK. Optimised, user-tested PIL versus standard PIL. Optimising participant information leaflets (e.g. through user-testing the leaflet with the target population to shape its content, format, and appearance) made little or no difference to recruitment: absolute improvement was 0% (95% CI 0% to 1%; 6 studies, 27,805 participants). The studies involved people in the UK. Only one study reported EDI data; participants were mostly older women. No cost or retention data were reported. We had moderate-certainty evidence for 13 other strategies; confidence was often reduced because the results came from single studies. Seven strategies involved changes to how potential participants received information; four involved changes to trial conduct; one targeted the recruiter or recruitment site; and one tested non-monetary incentives. We had much less confidence in the other 47 comparisons because the studies had design flaws, were single studies, or had very uncertain results. Costs were reported in only 17 of 91 studies. Strategy impact on retention was reported in 15 studies. All but one study (99%) were from high-income countries. The most reported demographics were age (49 studies), sex (32 studies), gender (27 studies), and education level (16 studies). AUTHORS' CONCLUSIONS: The evidence on strategies to improve trial recruitment remains broad but lacks depth. Of 65 strategies evaluated, only five were supported by high-certainty evidence. Open-label trial designs and telephone reminders to non-responders increased recruitment, while optimised participant information leaflets, recruitment primer letters, and multimedia information provided alongside a paper participant information leaflet had little or no effect. Reporting of participant characteristics was poor, limiting assessment of equity, diversity, and inclusion across most studies. Evidence is heavily skewed toward high-income countries. Future research must prioritise evaluations in low-to-middle-income settings and consistently report cost, retention, and EDI outcomes. We strongly urge the methodology research community to strengthen the evidence base by prioritising replications of existing strategies over the development and testing of new ones. FUNDING: National Institute for Health and Care Research (Advanced Fellowship, Adwoa Parker, reference:NIHR302256). Health Research Board, Republic of Ireland, Evidence Synthesis Ireland (grant ESI-2021-001) REGISTRATION: This review updates an earlier Cochrane review, which was first published in 2002 and subsequently updated in 2007, 2010, and 2018. Previous versions of the review and their protocols are available at: https://doi.org/10.1002/14651858.MR000013.pub2 https://doi.org/10.1002/14651858.MR000013.pub3 https://doi.org/10.1002/14651858.MR000013.pub4 https://doi.org/10.1002/14651858.MR000013.pub5 https://doi.org/10.1002/14651858.MR000013.pub6.

Randomized Controlled Trials as Topic↗
PubMed2006

Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability.

BACKGROUND: Generation Scotland: the Scottish Family Health Study aims to identify genetic variants accounting for variation in levels of quantitative traits underlying the major common complex diseases (such as cardiovascular disease, cognitive decline, mental illness) in Scotland. METHODS/DESIGN: Generation Scotland will recruit a family-based cohort of up to 50,000 individuals (comprising siblings and parent-offspring groups) across Scotland. It will be a six-year programme, beginning in Glasgow and Tayside in the first two years (Phase 1) before extending to other parts of Scotland in the remaining four years (Phase 2). In Phase 1, individuals aged between 35 and 55 years, living in the East and West of Scotland will be invited to participate, along with at least one (and preferably more) siblings and any other first degree relatives aged 18 or over. The total initial sample size will be 15,000 and it is planned that this will increase to 50,000 in Phase 2. All participants will be asked to contribute blood samples from which DNA will be extracted and stored for future investigation. The information from the DNA, along with answers to a life-style and medical history questionnaire, clinical and biochemical measurements taken at the time of donation, and subsequent health developments over the life course (traced through electronic health records) will be stored and used for research purposes. In addition, a detailed public consultation process will begin that will allow respondents' views to shape and develop the study. This is an important aspect to the research, and forms the continuation of a long-term parallel engagement process. DISCUSSION: As well as gene identification, the family-based study design will allow measurement of the heritability and familial aggregation of relevant quantitative traits, and the study of how genetic effects may vary by parent-of-origin. Long-term potential outcomes of this research include the targeting of disease prevention and treatment, and the development of screening tools based on the new genetic information. This study approach is complementary to other population-based genetic epidemiology studies, such as UK Biobank, which are established primarily to characterise genes and genetic risk in the population.

Adolescent↗
PubMed2006

Reducing door-to-antibiotic time in community-acquired pneumonia: Controlled before-and-after evaluation and cost-effectiveness analysis.

BACKGROUND: Practice guidelines suggest that all patients hospitalised with community-acquired pneumonia (CAP) should receive antibiotics within 4 h of admission. An audit at our hospital during 1999-2000 showed that this target was achieved in less than two thirds of patients with severe CAP. METHODS: An experienced multidisciplinary steering group designed a management pathway to improve the early delivery of appropriate antibiotics to patients with CAP. This was implemented using a multifaceted strategy. The effect of implementation was evaluated using a controlled before-and-after study design over two winter seasons (November-April 2001-2 and 2002-3). Cost-effectiveness analyses were performed from the hospital's perspective. RESULTS: The proportion of patients receiving appropriate antibiotics within 4 h of admission to hospital increased from 33% to 56% at the intervention site, and from 32% to 36% at the control site (absolute change adjusted for differences in severity of illness 17%, p = 0.035). The cost per additional patient receiving appropriate antibiotics within 4 h was 132 pound with no post-implementation evaluation, and 456 pound for a limited post-implementation evaluation. Simple modelling from the results of a large observational study suggests that the cost per death prevented could be 3003 pound with no post-implementation evaluation, or 16,632 pound with a limited post-implementation evaluation. CONCLUSIONS: The intervention markedly improved door-to-antibiotic time, albeit at considerable cost. It might still be a cost-effective strategy, however, to reduce mortality in CAP. Uncertainty about the cost effectiveness of such interventions is likely to be resolved only by a well-designed, cluster randomised trial.

Aged↗
PubMed2006

A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats.

The reproductive toxicity of curcumin, turmeric yellow, in Wistar rats was studied in order to generate additional relevant toxicity information for the use of curcumin in humans by oral administration. The two generation reproduction study was designed and conducted in accordance with OECD Guideline No. 416 [OECD, 1983. Guidelines for Testing of Chemicals, Guideline No. 416. Two Generation Reproduction Toxicity Study, adopted on 26th May 1983] and in compliance with Good Laboratory Practices (OECD, 1997 Principles of Good Laboratory Practice for the Testing of Chemicals. OECD, C(97)186/Final). The curcumin, mixed in the experimental diet at the concentrations of 1500, 3000 and 10,000 ppm was fed to three groups of rats, i.e., low, mid and high dose groups, and studied for two successive generations. A concurrent control group received experimental diet without the curcumin mixture. There were no treatment related adverse toxicological effects in the parental animals. No gross or microscopic changes were observed in any of the organs. None of the reproductive parameters were affected and there were no effects on the offspring other than a small reduction in pre-weaning body weight gain of the F2 pups at the highest dose level. It was concluded that the no observed adverse effect level (NOAEL) for reproductive toxicity of curcumin, fed in the diet for two successive generations to rats in this study was 10,000 ppm, which is equivalent to 847 and 959 mg/kg bodyweight (bw) per day for male rats and 1043 and 1076 for females for F0 and F1 generations, respectively. This study was the final toxicology study on curcumin reviewed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at the 61st Meeting, 2003. The JECFA group considered that the small body weight reduction in the F2 pups of the highest dose group prevented this from being regarded as a no adverse effect level, and so allocated an ADI for curcumin of 0-3 mg/kg bw based on the intake of 250-320 mg/kg bw in the mid-dose group as the NOEL.

Animals↗
PubMed2006

Analysis of referrals to a multi-disciplinary breast cancer genetics clinic: practical and economic considerations.

Analysis of activity was undertaken in an established regional clinic providing risk assessment, counselling, screening and management for women with a family history of breast or ovarian cancer. The objectives were to determine: (1) how closely the route and pattern of referrals matched official guidelines (2) whether the previously recorded socio-economic imbalance among clinic clientele persisted and (3) the economic and practical consequences of committing resources to verification and extension of reported family histories. The findings were: (1) after some years of operation, the proportion of referrals direct from primary care had increased from less than 50% to over 75%, with a concomitant slight decrease in overall referral rate; (2) the socio-economic distribution of patients referred had become less selective and (3) extension and verification of reported family histories led to a redistribution of risk categories, increasing the proportion of referrals judged to be in the "low risk" category, from 25% (based on referral letter alone) to 41% (at the end of the process). The costs associated with this approach are offset by the savings generated and it allows specialised counselling and screening services to be targeted more efficiently.

Breast Neoplasms↗
PubMed2006

How much does pre-trial testing influence complex intervention trials and would more testing make any difference? An email survey.

BACKGROUND: The UK Medical Research Council has proposed that complex interventions should be tested in exploratory trials prior to a full-scale trial so as to better define the intervention and test the feasibility of components such as recruitment. It is not clear to what extent this is being done. This study aimed to determine to what extent complex interventions are tested prior to a full-scale trial and whether more or different testing would have led to a different intervention being used in the trial. METHODS: Email survey of the authors of complex intervention trials published in seven major journals in 2004. RESULTS: 72% (50/69) of eligible authors replied. Eight authors did not consider their interventions to be complex. The majority of respondents' complex interventions were tested (34/42): some extensively. Conversely, only 17 of the 34 published reports describing these trials mention testing. Two-thirds (22/34) of those testing their interventions did not believe that more or different testing would have produced a more effective intervention. 31% (13/42) of all authors did believe further testing would have led to improvements. Five respondents mentioned a lack of funding as a reason for not doing more testing. CONCLUSION: Complex interventions are generally tested prior to their evaluation in a full-scale trial, although the amount of testing varies. Testing is often not described in trial reports, which makes it hard to judge whether a trial result could be improved with a better intervention, or whether further work with a different intervention is required.

Attitude of Health Personnel↗
PubMed2006

Is the involvement of opinion leaders in the implementation of research findings a feasible strategy?

BACKGROUND: There is only limited empirical evidence about the effectiveness of opinion leaders as health care change agents. AIM: To test the feasibility of identifying, and the characteristics of, opinion leaders using a sociometric instrument and a self-designating instrument in different professional groups within the UK National Health Service. DESIGN: Postal questionnaire survey. SETTING AND PARTICIPANTS: All general practitioners, practice nurses and practice managers in two regions of Scotland. All physicians and surgeons (junior hospital doctors and consultants) and medical and surgical nursing staff in two district general hospitals and one teaching hospital in Scotland, as well as all Scottish obstetric and gynaecology, and oncology consultants. RESULTS: Using the sociometric instrument, the extent of social networks and potential coverage of the study population in primary and secondary care was highly idiosyncratic. In contrast, relatively complex networks with good coverage rates were observed in both national specialty groups. Identified opinion leaders were more likely to have the expected characteristics of opinion leaders identified from diffusion and social influence theories. Moreover, opinion leaders appeared to be condition-specific. The self-designating instrument identified more opinion leaders, but it was not possible to estimate the extent and structure of social networks or likely coverage by opinion leaders. There was poor agreement in the responses to the sociometric and self-designating instruments. CONCLUSION: The feasibility of identifying opinion leaders using an off-the-shelf sociometric instrument is variable across different professional groups and settings within the NHS. Whilst it is possible to identify opinion leaders using a self-designating instrument, the effectiveness of such opinion leaders has not been rigorously tested in health care settings. Opinion leaders appear to be monomorphic (different leaders for different issues). Recruitment of opinion leaders is unlikely to be an effective general strategy across all settings and professional groups; the more specialised the group, the more opinion leaders may be a useful strategy.

Journal Article↗
PubMed2006

Receiver operating characteristics of the prostate specific antigen test in an unselected population.

OBJECTIVES: To determine the operating characteristics of prostate-specific antigen (PSA) testing and prostate cancer diagnosis rates in men who have had an initial PSA test in Tayside. SETTING: A retrospective cohort study in Tayside, Scotland from 1992 to 2001. METHODS: In total, 20,623 men were PSA tested during the period 1992-2001. After exclusions, 19,660 were studied. Sensitivity and specificity were calculated for various PSA cut-off values by age group using logistic regression weighted for verification bias (biopsy). Cox regression analysis was performed using six test pattern cohorts. RESULTS: The annual rate of PSA testing increased from 5.1 per 1000 man years in 1992 to 21.3 per 1000 man years in 2001. The average number of PSA tests per patient increased from 1.11 in 1992 to 2.57 in 2001. Prostate cancer diagnosis and death rates remained constant from 1995 onward. The PSA test had generally inadequate sensitivity and specificity values, so a unique cut-off could not be found for the two older age groups which could be used as a recommendation for biopsy. The commonly used 4 ng/mL cut-off was reasonably sensitive and specific only for the under 60 age group with values of 92.4% and 90.7%, respectively. For prostate cancer diagnosis, the hazard ratios (HR) were reported relative to those with a series of all normal tests. For those with an initially normal PSA test who had at least one abnormal retest result the HR for diagnosis was 10.43 (95% confidence interval [CI] 6.17-17.63). For those with initially abnormal tests with normal retests HR = 1.63 (95% CI 0.65-4.07). CONCLUSIONS: There are no optimal PSA cut-off values for older age groups with which to make a confident referral for biopsy. The increase in PSA testing and the questionable cut-off values of the test calls for the development of an alternative screening strategy.

Adult↗