Examining the effectiveness of different dental recall strategies on maintenance of optimum oral health: the INTERVAL dental recalls randomised controlled trial.

Objective To compare the clinical effectiveness of different frequencies of dental recall over a four-year period.Design A multi-centre, parallel-group, randomised controlled trial with blinded clinical outcome assessment. Participants were randomised to receive a dental check-up at six-monthly, 24-monthly or risk-based recall intervals. A two-strata trial design was used, with participants randomised within the 24-month stratum if the recruiting dentist considered them clinically suitable. Participants ineligible for 24-month recall were randomised to a risk-based or six-month recall interval.Setting UK primary dental care.Participants Practices providing NHS care and adults who had received regular dental check-ups.Main outcome measures The percentage of sites with gingival bleeding on probing, oral health-related quality of life (OHRQoL), cost-effectiveness.Results In total, 2,372 participants were recruited from 51 dental practices. Of those, 648 were eligible for the 24-month recall stratum and 1,724 participants were ineligible. There was no evidence of a significant difference in the mean percentage of sites with gingival bleeding on probing between intervention arms in any comparison. For those eligible for 24-month recall stratum: the 24-month versus six-month group had an adjusted mean difference of -0.91%, 95% CI (-5.02%, 3.20%); the 24-month group versus risk-based group had an adjusted mean difference of 0.07%, 95% CI (-3.99%, 4.12%). For the overall sample, the risk-based versus six-month adjusted mean difference was 0.78%, 95% CI (-1.17%, 2.72%). There was no evidence of a difference in OHRQoL (0-56 scale, higher score for poorer OHRQoL) between intervention arms in any comparison. For the overall sample, the risk-based versus six-month effect size was -0.35, 95% CI (-1.02, 0.32). There was no evidence of a clinically meaningful difference between the groups in any comparison in either eligibility stratum for any of the secondary clinical or patient-reported outcomes.Conclusion Over a four-year period, we found no evidence of a difference in oral health for participants allocated to a six-month or a risk-based recall interval, nor between a 24-month, six-month or risk-based recall interval for participants eligible for a 24-month recall. However, patients greatly value and are willing to pay for frequent dental check-ups.

Risk-based, 6-monthly and 24-monthly dental check-ups for adults: the INTERVAL three-arm RCT.

BACKGROUND: Traditionally, patients are encouraged to attend dental recall appointments at regular 6-month intervals, irrespective of their risk of developing dental disease. Stakeholders lack evidence of the relative effectiveness and cost-effectiveness of different recall strategies and the optimal recall interval for maintenance of oral health. OBJECTIVES: To test effectiveness and assess the cost-benefit of different dental recall intervals over a 4-year period. DESIGN: Multicentre, parallel-group, randomised controlled trial with blinded clinical outcome assessment at 4 years and a within-trial cost-benefit analysis. NHS and participant perspective costs were combined with benefits estimated from a general population discrete choice experiment. A two-stratum trial design was used, with participants randomised to the 24-month interval if the recruiting dentist considered them clinically suitable. Participants ineligible for 24-month recall were randomised to a risk-based or 6-month recall interval. SETTING: UK primary care dental practices. PARTICIPANTS: Adult, dentate, NHS patients who had visited their dentist in the previous 2 years. INTERVENTIONS: Participants were randomised to attend for a dental check-up at one of three dental recall intervals: 6-month, risk-based or 24-month recall. MAIN OUTCOMES: Clinical - gingival bleeding on probing; patient - oral health-related quality of life; economic - three analysis frameworks: (1) incremental cost per quality-adjusted life-year gained, (2) incremental net (societal) benefit and (3) incremental net (dental health) benefit. RESULTS: A total of 2372 participants were recruited from 51 dental practices; 648 participants were eligible for the 24-month recall stratum and 1724 participants were ineligible. There was no evidence of a significant difference in the mean percentage of sites with gingival bleeding between intervention arms in any comparison. For the eligible for 24-month recall stratum: the 24-month (n = 138) versus 6-month group (n = 135) had an adjusted mean difference of -0.91 (95% confidence interval -5.02 to 3.20); the risk-based (n = 143) versus 6-month group had an adjusted mean difference of -0.98 (95% confidence interval -5.05 to 3.09); the 24-month versus risk-based group had an adjusted mean difference of 0.07 (95% confidence interval -3.99 to 4.12). For the overall sample, the risk-based (n = 749) versus 6-month (n = 737) adjusted mean difference was 0.78 (95% confidence interval -1.17 to 2.72). There was no evidence of a difference in oral health-related quality of life between intervention arms in any comparison. For the economic evaluation, under framework 1 (cost per quality-adjusted life-year) the results were highly uncertain, and it was not possible to identify the optimal recall strategy. Under framework 2 (net societal benefit), 6-month recalls were the most efficient strategy with a probability of positive net benefit ranging from 78% to 100% across the eligible and combined strata, with findings driven by the high value placed on more frequent recall services in the discrete choice experiment. Under framework 3 (net dental health benefit), 24-month recalls were the most likely strategy to deliver positive net (dental health) benefit among those eligible for 24-month recall, with a probability of positive net benefit ranging from 65% to 99%. For the combined group, the optimal strategy was less clear. Risk-based recalls were more likely to be the most efficient recall strategy in scenarios where the costing perspective was widened to include participant-incurred costs, and in the Scottish subgroup. LIMITATIONS: Information regarding factors considered by dentists to inform the risk-based interval and the interaction with patients to determine risk and agree the interval were not collected. CONCLUSIONS: Over a 4-year period, we found no evidence of a difference in oral health for participants allocated to a 6-month or a risk-based recall interval, nor between a 24-month, 6-month or risk-based recall interval for participants eligible for a 24-month recall. However, people greatly value and are willing to pay for frequent dental check-ups; therefore, the most efficient recall strategy depends on the scope of the cost and benefit valuation that decision-makers wish to consider. FUTURE WORK: Assessment of the impact of risk assessment tools in informing risk-based interval decision-making and techniques for communicating a variable recall interval to patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95933794. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme [project numbers 06/35/05 (Phase I) and 06/35/99 (Phase II)] and will be published in full in Health Technology Assessment; Vol. 24, No. 60. See the NIHR Journals Library website for further project information.

Traditionally, dentists have encouraged both patients at low risk and patients at high risk of developing dental disease to attend their dental practices for regular 6-month 'check-ups'. There is, however, little evidence available for either patients or dentists to use when deciding on the best dental recall interval (i.e. time between dental check-ups) for maintaining oral health. In this study, we wanted to find out, for adult patients who regularly attend the dentist, what interval of time between dental check-ups maintains optimum oral health and represents value for money. A total of 2372 adults who regularly attended 51 different dental practices across Scotland, Northern Ireland, England and Wales were involved. Patients aged 18 years or over who received all or part of their care as NHS patients were randomly allocated to groups to receive a check-up either every 6 months, at an individualised recall interval based on their own risk of oral disease (risk-based recall), or every 24 months (if considered at low risk by their dentist). The recruited adults completed questionnaires at their first trial appointment and then every year of the 4-year study. Their attendance at recall appointments was recorded and they received a clinical assessment taken by study staff at the end of their involvement at year 4. After 4 years, there was no evidence of a difference in the oral health of patients allocated to a 6-month or variable risk-based recall interval. For patients considered by their dentists to be suitable for a 24-month recall interval, there was no difference between those in the 24-month, 6-month or risk-based recall intervals. However, people greatly value and are willing to pay for frequent dental check-ups. The recall strategy that offers the best value for money to patients and the NHS, therefore, depends on what people and decision-makers wish to value within a health-care system.

Where do we go from here? - Opportunities and barriers to the career development of trial managers: a survey of UK-based trial management professionals.

BACKGROUND: Clinical trials commonly have a dedicated trial manager and effective trial management is essential to the successful delivery of high-quality trials. Trial managers have diverse experience and currently there is no standardised structured career pathway. The UK Trial Managers' Network (UKTMN) surveyed its members to understand what is important to them with respect to career development since this would be important in the development of any initiative intended to develop a skilled workforce. METHODS: We conducted an online survey of UKTMN members, who are trial management professionals, working on academic-led trials in the UK. Members were asked what they perceive as opportunities and barriers to career development. Two reminders were sent to facilitate completion of the survey, and responders were offered the opportunity to enter a prize draw for waived fees at the UKTMN annual meeting. Data were analysed descriptively by using Stata (version 15.1), and free-text responses were reviewed for themes. RESULTS: The survey was sent to 819 UKTMN members; 433 responses were received, although 13 were from non-UKTMN members; thus 420 respondents' data were included in analyses. Respondents were representative of UKTMN membership; however, more responses were received by trial managers based in registered clinical trials units (CTUs). The top three opportunities for career development were (i) training, (ii) helping design trials and (iii) undertaking relevant qualifications. The top three barriers were (i) funding, (ii) few opportunities to get involved in development activities aside from managing a trial and (iii) unclear organisational career pathway. Almost all respondents (401/420, 95.4%) considered career development either very or quite important. Although all respondents had a day-to-day role in managing trials, there was huge disparity between job titles. CONCLUSION: Career development is important to trial managers yet there is a lack of a structured pathway. The enablers and disablers to career development for trial managers should be clearly considered by the clinical trial community and, in particular, employers, sponsors and funders in order to develop a highly skilled workforce of trial managers, who are key to the delivery of trials.

Improving the Quality of Dentistry (IQuaD): a cluster factorial randomised controlled trial comparing the effectiveness and cost-benefit of oral hygiene advice and/or periodontal instrumentation with routine care for the prevention and management of periodontal disease in dentate adults attending dental primary care.

BACKGROUND: Periodontal disease is preventable but remains the most common oral disease worldwide, with major health and economic implications. Stakeholders lack reliable evidence of the relative clinical effectiveness and cost-effectiveness of different types of oral hygiene advice (OHA) and the optimal frequency of periodontal instrumentation (PI). OBJECTIVES: To test clinical effectiveness and assess the economic value of the following strategies: personalised OHA versus routine OHA, 12-monthly PI (scale and polish) compared with 6-monthly PI, and no PI compared with 6-monthly PI. DESIGN: Multicentre, pragmatic split-plot, randomised open trial with a cluster factorial design and blinded outcome evaluation with 3 years' follow-up and a within-trial cost-benefit analysis. NHS and participant costs were combined with benefits [willingness to pay (WTP)] estimated from a discrete choice experiment (DCE). SETTING: UK dental practices. PARTICIPANTS: Adult dentate NHS patients, regular attenders, with Basic Periodontal Examination (BPE) scores of 0, 1, 2 or 3. INTERVENTION: Practices were randomised to provide routine or personalised OHA. Within each practice, participants were randomised to the following groups: no PI, 12-monthly PI or 6-monthly PI (current practice). MAIN OUTCOME MEASURES: Clinical - gingival inflammation/bleeding on probing at the gingival margin (3 years). Patient - oral hygiene self-efficacy (3 years). Economic - net benefits (mean WTP minus mean costs). RESULTS: A total of 63 dental practices and 1877 participants were recruited. The mean number of teeth and percentage of bleeding sites was 24 and 33%, respectively. Two-thirds of participants had BPE scores of ≤ 2. Under intention-to-treat analysis, there was no evidence of a difference in gingival inflammation/bleeding between the 6-monthly PI group and the no-PI group [difference 0.87%, 95% confidence interval (CI) -1.6% to 3.3%; p = 0.481] or between the 6-monthly PI group and the 12-monthly PI group (difference 0.11%, 95% CI -2.3% to 2.5%; p = 0.929). There was also no evidence of a difference between personalised and routine OHA (difference -2.5%, 95% CI -8.3% to 3.3%; p = 0.393). There was no evidence of a difference in self-efficacy between the 6-monthly PI group and the no-PI group (difference -0.028, 95% CI -0.119 to 0.063; p = 0.543) and no evidence of a clinically important difference between the 6-monthly PI group and the 12-monthly PI group (difference -0.097, 95% CI -0.188 to -0.006; p = 0.037). Compared with standard care, no PI with personalised OHA had the greatest cost savings: NHS perspective -£15 (95% CI -£34 to £4) and participant perspective -£64 (95% CI -£112 to -£16). The DCE shows that the general population value these services greatly. Personalised OHA with 6-monthly PI had the greatest incremental net benefit [£48 (95% CI £22 to £74)]. Sensitivity analyses did not change conclusions. LIMITATIONS: Being a pragmatic trial, we did not deny PIs to the no-PI group; there was clear separation in the mean number of PIs between groups. CONCLUSIONS: There was no additional benefit from scheduling 6-monthly or 12-monthly PIs over not providing this treatment unless desired or recommended, and no difference between OHA delivery for gingival inflammation/bleeding and patient-centred outcomes. However, participants valued, and were willing to pay for, both interventions, with greater financial value placed on PI than on OHA. FUTURE WORK: Assess the clinical effectiveness and cost-effectiveness of providing multifaceted periodontal care packages in primary dental care for those with periodontitis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56465715. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 38. See the NIHR Journals Library website for further project information.

Reflecting on the methodological challenges of recruiting to a United Kingdom-wide, multi-centre, randomised controlled trial in gynaecology outpatient settings.

BACKGROUND: Successful recruitment of participants to any trial is central to its success. Trial results are routinely published, and recruitment is often cited to be slower and more difficult than anticipated. This article reflects on the methodological challenges of recruiting women with prolapse attending United Kingdom (UK) gynaecology outpatient clinics to a multi-centre randomised controlled trial (RCT) of physiotherapy, and the systems put in place in an attempt to address them. METHODS: Gynaecology outpatients with symptomatic prolapse were to be recruited over a 16-month period from 14 UK hospitals and one New Zealand hospital. Eligible women were informed about the trial by their gynaecologist and informed consent was obtained by the central trial office. Recruitment difficulties were encountered early on, and a number of strategies were employed to try to improve recruitment. RESULTS: Some strategies were more successful than others and they differed in the resources required. Actions that facilitated recruitment included increasing recruiting centres to 23 UK and two international hospitals, good centre support, using processes embedded in clinical practice, and good communication between the trial office, collaborators and participants. Collaborator incentives, whereby staff involved received the benefit immediately, were more successful than a nominal monetary payment per woman randomised. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to receive active treatment rather than allocation to the control group, lack of support staff and high staff turnover. Geographical variations in Primary Care Trust Research Management and Governance approval systems and general practitioner (GP) referral procedures also impacted negatively on recruitment. CONCLUSIONS: Our article reflects on the methodological challenges of recruiting to a multi-centre RCT in a UK gynaecology setting. Effective interventions included increasing the number of recruiting centres and providing collaborator incentives. Barriers to recruitment included fewer eligible women than anticipated, patient's preference to be allocated to the treatment group, lack of support staff, and variations in approval systems and GP referral procedures. To improve the evidence base on clinical trial recruitment, trialists need to publish their experiences and lessons learned. Future RCTs should evaluate, where possible, the effect of strategies designed to improve recruitment and retention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN35911035.

IQuaD dental trial; improving the quality of dentistry: a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care.

BACKGROUND: Periodontal disease is the most common oral disease affecting adults, and although it is largely preventable it remains the major cause of poor oral health worldwide. Accumulation of microbial dental plaque is the primary aetiological factor for both periodontal disease and caries. Effective self-care (tooth brushing and interdental aids) for plaque control and removal of risk factors such as calculus, which can only be removed by periodontal instrumentation (PI), are considered necessary to prevent and treat periodontal disease thereby maintaining periodontal health. Despite evidence of an association between sustained, good oral hygiene and a low incidence of periodontal disease and caries in adults there is a lack of strong and reliable evidence to inform clinicians of the relative effectiveness (if any) of different types of Oral Hygiene Advice (OHA). The evidence to inform clinicians of the effectiveness and optimal frequency of PI is also mixed. There is therefore an urgent need to assess the relative effectiveness of OHA and PI in a robust, sufficiently powered randomised controlled trial (RCT) in primary dental care. METHODS/DESIGN: This is a 5 year multi-centre, randomised, open trial with blinded outcome evaluation based in dental primary care in Scotland and the North East of England. Practitioners will recruit 1860 adult patients, with periodontal health, gingivitis or moderate periodontitis (Basic Periodontal Examination Score 0-3). Dental practices will be cluster randomised to provide routine OHA or Personalised OHA. To test the effects of PI each individual patient participant will be randomised to one of three groups: no PI, 6 monthly PI (current practice), or 12 monthly PI.Baseline measures and outcome data (during a three year follow-up) will be assessed through clinical examination, patient questionnaires and NHS databases.The primary outcome measures at 3 year follow up are gingival inflammation/bleeding on probing at the gingival margin; oral hygiene self-efficacy and net benefits. DISCUSSION: IQuaD will provide evidence for the most clinically-effective and cost-effective approach to managing periodontal disease in dentate adults in Primary Care. This will support general dental practitioners and patients in treatment decision making. TRIAL REGISTRATION: Protocol ID: ISRCTN56465715.

Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial).

CONTEXT: Vitamin D or calcium supplementation may have effects on vascular disease and cancer. OBJECTIVE: Our objective was to investigate whether vitamin D or calcium supplementation affects mortality, vascular disease, and cancer in older people. DESIGN AND SETTING: The study included long-term follow-up of participants in a two by two factorial, randomized controlled trial from 21 orthopedic centers in the United Kingdom. PARTICIPANTS: Participants were 5292 people (85% women) aged at least 70 yr with previous low-trauma fracture. INTERVENTIONS: Participants were randomly allocated to daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention. MAIN OUTCOME MEASURES: All-cause mortality, vascular disease mortality, cancer mortality, and cancer incidence were evaluated. RESULTS: In intention-to-treat analyses, mortality [hazard ratio (HR) = 0.93; 95% confidence interval (CI) = 0.85-1.02], vascular disease mortality (HR = 0.91; 95% CI = 0.79-1.05), cancer mortality (HR = 0.85; 95% CI = 0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25) did not differ significantly between participants allocated vitamin D and those not. All-cause mortality (HR = 1.03; 95% CI = 0.94-1.13), vascular disease mortality (HR = 1.07; 95% CI = 0.92-1.24), cancer mortality (HR = 1.13; 95% CI = 0.91-1.40), and cancer incidence (HR = 1.06; 95% CI = 0.91-1.23) also did not differ significantly between participants allocated calcium and those not. In a post hoc statistical analysis adjusting for compliance, thus with fewer participants, trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated, although all results remain nonsignificant. CONCLUSIONS: Daily vitamin D or calcium supplementation did not affect mortality, vascular disease, cancer mortality, or cancer incidence.

Using a business model approach and marketing techniques for recruitment to clinical trials.

Randomised controlled trials (RCTs) are generally regarded as the gold standard for evaluating health care interventions. The level of uncertainty around a trial's estimate of effect is, however, frequently linked to how successful the trial has been in recruiting and retaining participants. As recruitment is often slower or more difficult than expected, with many trials failing to reach their target sample size within the timescale and funding originally envisaged, the results are often less reliable than they could have been. The high number of trials that require an extension to the recruitment period in order to reach the required sample size potentially delays the introduction of more effective therapies into routine clinical practice. Moreover, it may result in less research being undertaken as resources are redirected to extending existing trials rather than funding additional studies.Poor recruitment to publicly-funded RCTs has been much debated but there remains remarkably little clear evidence as to why many trials fail to recruit well, which recruitment methods work, in which populations and settings and for what type of intervention. One proposed solution to improving recruitment and retention is to adopt methodology from the business world to inform and structure trial management techniques.We review what is known about interventions to improve recruitment to trials. We describe a proposed business approach to trials and discuss the implementation of using a business model, using insights gained from three case studies.

Marketing and clinical trials: a case study.

BACKGROUND: Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. METHODS: Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. RESULTS: The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. CONCLUSION: The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

BACKGROUND: Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). METHODS: In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. RESULTS: The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. CONCLUSION: This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies.

BACKGROUND: A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme. METHODS: The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate. RESULTS: Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed. CONCLUSION: Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone.