Pharmaceutical policies: effects of regulating drug insurance schemes.

BACKGROUND: Drug insurance schemes are systems that provide access to medicines on a prepaid basis and could potentially improve access to essential medicines and reduce out-of-pocket payments for vulnerable populations. OBJECTIVES: To assess the effects on drug use, drug expenditure, healthcare utilisation and healthcare outcomes of alternative policies for regulating drug insurance schemes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases, and two trials registers between November 2014 and September 2020, including a citation search for included studies on 15 September 2021 using Web of Science. We screened reference lists of all the relevant reports that we retrieved and reports from the Background section. Authors of relevant papers, relevant organisations, and discussion lists were contacted to identify additional studies, including unpublished and ongoing studies. SELECTION CRITERIA: We planned to include randomised trials, non-randomised trials, interrupted time-series studies (including controlled ITS [CITS] and repeated measures [RM] studies), and controlled before-after (CBA) studies. Two review authors independently assessed the search results and reference lists of relevant reports, retrieved the full text of potentially relevant references and independently applied the inclusion criteria to those studies. We resolved disagreements by discussion, and when necessary by including a third review author. We excluded studies of the following pharmaceutical policies covered in other Cochrane Reviews: those that determined how decisions were made about which conditions or drugs were covered; those that placed restrictions on reimbursement for drugs that were covered; and those that regulated out-of-pocket payments for drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included studies and assessed risk of bias for each study, with disagreements being resolved by consensus. We used the criteria suggested by  Cochrane Effective Practice and Organisation of Care (EPOC)  to assess the risk of bias of included studies. For randomised trials, non-randomised trials and controlled before-after studies, we planned to report relative effects. For dichotomous outcomes, we reported the risk ratio (RR) when possible and adjusted for baseline differences in the outcome measures. For interrupted time series and controlled interrupted time-series studies, we computed changes along two dimensions: change in level; and change in slope. We undertook a structured synthesis following the EPOC guidance on this topic, describing the range of effects found in the studies for each category of outcomes. MAIN RESULTS: We identified 58 studies that met the inclusion criteria (25 interrupted time-series studies and 33 controlled before-after studies). Most of the studies (54) assessed a single policy implemented in the United States (US) healthcare system: Medicare Part D. The other four assessed other drug insurance schemes from Canada and the US, but only one of them provided analysable data for inclusion in the quantitative synthesis. The introduction of drug insurance schemes may increase prescription drug use (low-certainty evidence). On the other hand, Medicare Part D may decrease drug expenditure measured as both out-of-pocket spending and total drug spending (low-certainty evidence). Regarding healthcare utilisation, drug insurance policies (such as Medicare Part D) may lead to a small increase in visits to the emergency department. However, it is uncertain whether this type of policy increases or decreases hospital admissions or outpatient visits by beneficiaries of the scheme because the certainty of the evidence was very low. Likewise, it is uncertain if the policy increases or reduces health outcomes such as mortality because the certainty of the evidence was very low. AUTHORS' CONCLUSIONS: The introduction of drug insurance schemes such as Medicare Part D in the US health system may increase prescription drug use and may decrease out-of-pocket payments by the beneficiaries of the scheme and total drug expenditures. It may also lead to a small increase in visits to the emergency department by the beneficiaries of the policy. Its effects on other healthcare utilisation outcomes and on health outcomes are uncertain because of the very low certainty of the evidence. The applicability of this evidence to settings outside US healthcare is limited.

Early detection of neovascular age-related macular degeneration: an economic evaluation based on data from the EDNA study.

BACKGROUND/AIMS: To evaluate the cost-effectiveness of non-invasive monitoring tests to detect the onset of neovascular age-related macular degeneration (nAMD) in the unaffected second eye of patients receiving treatment for unilateral nAMD in a UK National Health Service (NHS) hospital outpatient setting. METHODS: A patient-level state transition model was constructed to simulate the onset, detection, and treatment of nAMD in the second eye. Five index tests were compared: self-reported change in visual function, Amsler test, clinic measured change in visual acuity from baseline, fundus assessment by clinical examination or colour photography, and spectral domain optical coherence tomography (SD-OCT). Diagnosis of nAMD was confirmed by fundus fluorescein angiography (FFA) before prompt initiation of antivascular endothelial growth factor treatment. Quality-adjusted life-years (QALYs) and costs of health and social care were modelled over a 25-year time horizon. RESULTS: SD-OCT generated more QALYs (SD-OCT, 5.830; fundus assessment, 5.787; Amsler grid, 5.736, patient's subjective assessment, 5.630; and visual acuity, 5.600) and lower health and social care costs (SD-OCT, £19 406; fundus assessment, £19 649; Amsler grid, £19 751; patient's subjective assessment, £20 198 and visual acuity, £20 444) per patient compared with other individual monitoring tests. Probabilistic sensitivity analysis indicated a high probability (97%-99%) of SD-OCT being the preferred test across a range of cost-effectiveness thresholds (£13 000-£30 000) applied in the UK NHS. CONCLUSIONS: Early treatment of the second eye following FFA confirmation of SD-OCT positive findings is expected to maintain better visual acuity and health-related quality of life and may reduce costs of health and social care over the lifetime of patients.

Selective Caries Removal in Permanent Teeth (SCRiPT) for the treatment of deep carious lesions: a randomised controlled clinical trial in primary care.

BACKGROUND: Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth. METHOD: This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes. DISCUSSION: SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN. TRIAL REGISTRATION NUMBER: ISRCTN76503940. Date of Registration: 30.10.2019. URL of trial registry record: https://www.isrctn.com/ISRCTN76503940?q=ISRCTN76503940%20&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search .

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.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

INTERVAL (investigation of NICE technologies for enabling risk-variable-adjusted-length) dental recalls trial: a multicentre randomised controlled trial investigating the best dental recall interval for optimum, cost-effective maintenance of oral health in dentate adults attending dental primary care.

BACKGROUND: Traditionally, patients at low risk and high risk of developing dental disease have been encouraged to attend dental recall appointments at regular intervals of six months between appointments. The lack of evidence for the effect that different recall intervals between dental check-ups have on patient outcomes, provider workload and healthcare costs is causing considerable uncertainty for the profession and patients, despite the publication of the NICE Guideline on dental recall. The need for primary research has been highlighted in the Health Technology Assessment Group's systematic review of routine dental check-ups, which found little evidence to support or refute the practice of encouraging 6-monthly dental check-ups in adults. The more recent Cochrane review on recall interval concluded there was insufficient evidence to draw any conclusions regarding the potential beneficial or harmful effects of altering the recall interval between dental check-ups. There is therefore an urgent need to assess the relative effectiveness and cost-benefit of different dental recall intervals in a robust, sufficiently powered randomised control trial (RCT) in primary dental care. METHODS: This is a four year multi-centre, parallel-group, randomised controlled trial with blinded outcome assessment based in dental primary care in the UK. Practitioners will recruit 2372 dentate adult patients. Patient participants will be randomised to one of three groups: fixed-period six month recall, risk-based recall, or fixed-period twenty-four month recall. Outcome data will be assessed through clinical examination, patient questionnaires and NHS databases. The primary outcomes measure gingival inflammation/bleeding on probing and oral health-related quality of life. DISCUSSION: INTERVAL will provide evidence for the most clinically-effective and cost-beneficial recall interval for maintaining optimum oral health in dentate adults attending general dental practice. TRIAL REGISTRATION: ISRCTN95933794 (Date assigned 20/08/2008).

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.

Barriers and facilitators of evidence-based management of patients with bacterial infections among general dental practitioners: a theory-informed interview study.

BACKGROUND: General dental practitioners (GDPs) regularly prescribe antibiotics to manage dental infections although most infections can be treated successfully by local measures. Published guidance to support GDPs to make appropriate prescribing decisions exists but there continues to be wide variation in dental antibiotic prescribing. An interview study was conducted as part of the Reducing Antibiotic Prescribing in Dentistry (RAPiD) trial to understand the barriers and facilitators of using local measures instead of prescribing antibiotics to manage bacterial infections. METHODS: Thirty semi-structured one-to-one telephone interviews were conducted using the Theoretical Domains Framework (TDF). Responses were coded into domains of the TDF and sub-themes. Priority domains (high frequency: ≥50 % interviewees discussed) relevant to behaviour change were identified as targets for future intervention efforts and mapped onto 'intervention functions' of the Behaviour Change Wheel system. RESULTS: Five domains (behavioural regulation, social influences, reinforcement, environmental context and resources, and beliefs about consequences) with seven sub-themes were identified as targets for future intervention. All participants had knowledge about the evidence-based management of bacterial infections, but they reported difficulties in following this due to patient factors and time management. Lack of time was found to significantly influence their decision processes with regard to performing local measures. Beliefs about their capabilities to overcome patient influence, beliefs that performing local measures would impact on subsequent appointment times as well as there being no incentives for performing local measures were also featured. Though no knowledge or basic skills issues were identified, the participants suggested some continuous professional development programmes (e.g. time management, an overview of published guidance) to address some of the barriers. The domain results suggest a number of intervention functions through which future interventions could change GDPs' antibiotic prescribing for bacterial infections: imparting skills through training, providing an example for GDPs to imitate (i.e. modelling) or creating the expectation of a reward (i.e. incentivisation). CONCLUSIONS: This is the first theoretically informed study to identify barriers and facilitators of evidence-based management of patients with bacterial infections among GDPs. A pragmatic approach is needed to address the modifiable barriers in future interventions intended to change dentists' inappropriate prescribing behaviour.

Clinical effectiveness and cost-effectiveness of open and arthroscopic rotator cuff repair [the UK Rotator Cuff Surgery (UKUFF) randomised trial].

BACKGROUND: Uncertainty exists regarding the best management of patients with degenerative tears of the rotator cuff. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of arthroscopic and open rotator cuff repair in patients aged ≥ 50 years with degenerative rotator cuff tendon tears. DESIGN: Two parallel-group randomised controlled trial. SETTING: Nineteen teaching and district general hospitals in the UK. PARTICIPANTS: Patients (n = 273) aged ≥ 50 years with degenerative rotator cuff tendon tears. INTERVENTIONS: Arthroscopic surgery and open rotator cuff repair, with surgeons using their usual and preferred method of arthroscopic or open repair. Follow-up was by telephone questionnaire at 2 and 8 weeks after surgery and by postal questionnaire at 8, 12 and 24 months after randomisation. MAIN OUTCOME MEASURES: The Oxford Shoulder Score (OSS) at 24 months was the primary outcome measure. Magnetic resonance imaging evaluation of the shoulder was made at 12 months after surgery to assess the integrity of the repair. RESULTS: The mean OSS improved from 26.3 [standard deviation (SD) 8.2] at baseline to 41.7 (SD 7.9) at 24 months for arthroscopic surgery and from 25.0 (SD 8.0) at baseline to 41.5 (SD 7.9) at 24 months for open surgery. When effect sizes are shown for the intervention, a negative sign indicates that an open procedure is favoured. For the intention-to-treat analysis, there was no statistical difference between the groups, the difference in OSS score at 24 months was -0.76 [95% confidence interval (CI) -2.75 to 1.22; p = 0.452] and the CI excluded the predetermined clinically important difference in the OSS of 3 points. There was also no statistical difference when the groups were compared per protocol (difference in OSS score -0.46, 95% CI -5.30 to 4.39; p = 0.854). The questionnaire response rate was > 86%. At 8 months, 77% of participants reported that shoulder problems were much or slightly better, and at 24 months this increased to 85%. There were no significant differences in mean cost between the arthroscopic group and the open repair group for any of the component resource-use categories, nor for the total follow-up costs at 24 months. The overall treatment cost at 2 years was £2567 (SD £176) for arthroscopic surgery and £2699 (SD £149) for open surgery, according to intention-to-treat analysis. For the per-protocol analysis there was a significant difference in total initial procedure-related costs between the arthroscopic group and the open repair group, with arthroscopic repair being more costly by £371 (95% CI £135 to £607). Total quality-adjusted life-years accrued at 24 months averaged 1.34 (SD 0.05) in the arthroscopic repair group and 1.35 (SD 0.05) in the open repair group, a non-significant difference of 0.01 (95% CI -0.11 to 0.10). The rate of re-tear was not significantly different across the randomised groups (46.4% and 38.6% for arthroscopic and open surgery, respectively). The participants with tears that were impossible to repair had the lowest OSSs, the participants with re-tears had slightly higher OSSs and the participants with healed repairs had the most improved OSSs. These findings were the same when analysed per protocol. CONCLUSION: In patients aged > 50 years with a degenerative rotator cuff tear there is no difference in clinical effectiveness or cost-effectiveness between open repair and arthroscopic repair at 2 years for the primary outcome (OSS) and all other prespecified secondary outcomes. Future work should explore new methods to improve tendon healing and reduce the high rate of re-tears observed in this trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97804283. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 80. See the NIHR Journals Library website for further project information.

Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.

BACKGROUND: For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. DATA SOURCES: MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. REVIEW METHODS: Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. RESULTS: The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. LIMITATIONS: The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS: The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002461. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The clinical effectiveness and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice: systematic review and economic evaluation.

BACKGROUND: Self-monitoring (self-testing and self-management) could be a valid option for oral anticoagulation therapy monitoring in the NHS, but current evidence on its clinical effectiveness or cost-effectiveness is limited. OBJECTIVES: We investigated the clinical effectiveness and cost-effectiveness of point-of-care coagulometers for the self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy, compared with standard clinic monitoring. DATA SOURCES: We searched major electronic databases (e.g. MEDLINE, MEDLINE In Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service, Science Citation Index and Cochrane Central Register of Controlled Trials) from 2007 to May 2013. Reports published before 2007 were identified from the existing Cochrane review (major databases searched from inception to 2007). The economic model parameters were derived from the clinical effectiveness review, other relevant reviews, routine sources of cost data and clinical experts' advice. REVIEW METHODS: We assessed randomised controlled trials (RCTs) evaluating self-monitoring in people with atrial fibrillation or heart valve disease requiring long-term anticoagulation therapy. CoaguChek(®) XS and S models (Roche Diagnostics, Basel, Switzerland), INRatio2(®) PT/INR monitor (Alere Inc., San Diego, CA USA), and ProTime Microcoagulation system(®) (International Technidyne Corporation, Nexus Dx, Edison, NJ, USA) coagulometers were compared with standard monitoring. Where possible, we combined data from included trials using standard inverse variance methods. Risk of bias assessment was performed using the Cochrane risk of bias tool. A de novo economic model was developed to assess the cost-effectiveness over a 10-year period. RESULTS: We identified 26 RCTs (published in 45 papers) with a total of 8763 participants. CoaguChek was used in 85% of the trials. Primary analyses were based on data from 21 out of 26 trials. Only four trials were at low risk of bias. Major clinical events: self-monitoring was significantly better than standard monitoring in preventing thromboembolic events [relative risk (RR) 0.58, 95% confidence interval (CI) 0.40 to 0.84; p = 0.004]. In people with artificial heart valves (AHVs), self-monitoring almost halved the risk of thromboembolic events (RR 0.56, 95% CI 0.38 to 0.82; p = 0.003) and all-cause mortality (RR 0.54, 95% CI 0.32 to 0.92; p = 0.02). There was greater reduction in thromboembolic events and all-cause mortality through self-management but not through self-testing. Intermediate outcomes: self-testing, but not self-management, showed a modest but significantly higher percentage of time in therapeutic range, compared with standard care (weighted mean difference 4.44, 95% CI 1.71 to 7.18; p = 0.02). Patient-reported outcomes: improvements in patients' quality of life related to self-monitoring were observed in six out of nine trials. High preference rates were reported for self-monitoring (77% to 98% in four trials). Net health and social care costs over 10 years were £7295 (self-monitoring with INRatio2); £7324 (standard care monitoring); £7333 (self-monitoring with CoaguChek XS) and £8609 (self-monitoring with ProTime). The estimated quality-adjusted life-year (QALY) gain associated with self-monitoring was 0.03. Self-monitoring with INRatio2 or CoaguChek XS was found to have ≈ 80% chance of being cost-effective, compared with standard monitoring at a willingness-to-pay threshold of £20,000 per QALY gained. CONCLUSIONS: Compared with standard monitoring, self-monitoring appears to be safe and effective, especially for people with AHVs. Self-monitoring, and in particular self-management, of anticoagulation status appeared cost-effective when pooled estimates of clinical effectiveness were applied. However, if self-monitoring does not result in significant reductions in thromboembolic events, it is unlikely to be cost-effective, based on a comparison of annual monitoring costs alone. Trials investigating the longer-term outcomes of self-management are needed, as well as direct comparisons of the various point-of-care coagulometers. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013004944. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation.

OBJECTIVES: To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. DESIGN: Systematic review of current evidence and economic modelling. DATA SOURCES: Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered. RESULTS: 26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p ≤ 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were £7324 with standard care and £7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have ∼ 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of £20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not. CONCLUSIONS: Self-monitoring appears to be a safe and cost-effective option. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013004944.

Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.

BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. RESULTS: The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS: Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. FUTURE WORK: Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51995477. 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. 19, No. 27. See the NIHR Journals Library website for further project information.

Optical coherence tomography for the monitoring of neovascular age-related macular degeneration: a systematic review.

TOPIC: To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. CLINICAL RELEVANCE: Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. METHODS: Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. RESULTS: We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%-93%) and 48% (95% CI, 30%-67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. CONCLUSIONS: There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

A randomized trial comparing treatments for varicose veins.

BACKGROUND: Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. METHODS: In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. RESULTS: After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P=0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (P<0.001); the frequency of serious adverse events (approximately 3%) was similar among the groups. Measures of clinical success were similar among the groups, but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group (P<0.001). CONCLUSIONS: Quality-of-life measures were generally similar among the study groups, with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.).

Assessing methods to specify the target difference for a randomised controlled trial: DELTA (Difference ELicitation in TriAls) review.

BACKGROUND: The randomised controlled trial (RCT) is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to the design and validity of a RCT is a calculation of the number of participants needed (the sample size). The value used to determine the sample size can be considered the 'target difference'. From both a scientific and an ethical standpoint, selecting an appropriate target difference is of crucial importance. Determination of the target difference, as opposed to statistical approaches to calculating the sample size, has been greatly neglected though a variety of approaches have been proposed the current state of the evidence is unclear. OBJECTIVES: The aim was to provide an overview of the current evidence regarding specifying the target difference in a RCT sample size calculation. The specific objectives were to conduct a systematic review of methods for specifying a target difference; to evaluate current practice by surveying triallists; to develop guidance on specifying the target difference in a RCT; and to identify future research needs. DESIGN: The biomedical and social science databases searched were MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, Education Resources Information Center (ERIC) and Scopus for in-press publications. All were searched from 1966 or the earliest date of the database coverage and searches were undertaken between November 2010 and January 2011. There were three interlinked components: (1) systematic review of methods for specifying a target difference for RCTs - a comprehensive search strategy involving an electronic literature search of biomedical and some non-biomedical databases and clinical trials textbooks was carried out; (2) identification of current trial practice using two surveys of triallists - members of the Society for Clinical Trials (SCT) were invited to complete an online survey and respondents were asked about their awareness and use of, and willingness to recommend, methods; one individual per triallist group [UK Clinical Research Collaboration (UKCRC)-registered Clinical Trials Units (CTUs), Medical Research Council (MRC) UK Hubs for Trials Methodology Research and National Institute for Health Research (NIHR) UK Research Design Services (RDS)] was invited to complete a survey; (3) production of a structured guidance document to aid the design of future trials - the draft guidance was developed utilising the results of the systematic review and surveys by the project steering and advisory groups. SETTING: Methodological review incorporating electronic searches, review of books and guidelines, two surveys of experts (membership of an international society and UK- and Ireland-based triallists) and development of guidance. PARTICIPANTS: The two surveys were sent out to membership of the SCT and UK- and Ireland-based triallists. INTERVENTIONS: The review focused on methods for specifying the target difference in a RCT. It was not restricted to any type of intervention or condition. MAIN OUTCOME MEASURES: Methods for specifying the target difference for a RCT were considered. RESULTS: The search identified 11,485 potentially relevant studies. In total, 1434 were selected for full-text assessment and 777 were included in the review. Seven methods to specify the target difference for a RCT were identified - anchor, distribution, health economic, opinion-seeking, pilot study, review of evidence base (RoEB) and standardised effect size (SES) - each having important variations in implementation. A total of 216 of the included studies used more than one method. A total of 180 (15%) responses to the SCT survey were received, representing 13 countries. Awareness of methods ranged from 38% (n =69) for the health economic method to 90% (n =162) for the pilot study. Of the 61 surveys sent out to UK triallist groups, 34 (56%) responses were received. Awareness ranged from 97% (n =33) for the RoEB and pilot study methods to only 41% (n =14) for the distribution method. Based on the most recent trial, all bar three groups (91%, n =30) used a formal method. Guidance was developed on the use of each method and the reporting of the sample size calculation in a trial protocol and results paper. CONCLUSIONS: There is a clear need for greater use of formal methods to determine the target difference and better reporting of its specification. Raising the standard of RCT sample size calculations and the corresponding reporting of them would aid health professionals, patients, researchers and funders in judging the strength of the evidence and ensuring better use of scarce resources. FUNDING: The Medical Research Council UK and the National Institute for Health Research Joint Methodology Research programme.

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.

Pharmaceutical policies: effects of restrictions on reimbursement.

BACKGROUND: Public policy makers and benefit plan managers need to restrain rising pharmaceutical drug costs while preserving access and optimizing health benefits. OBJECTIVES: To determine the effects of a pharmaceutical policy restricting the reimbursement of selected medications on drug use, health care utilization, health outcomes and costs (expenditures). SEARCH STRATEGY: We searched the 14 major bibliographic databases and websites (to January 2009). SELECTION CRITERIA: Included were studies of pharmaceutical policies that restrict coverage and reimbursement of selected drugs or drug classes, often using additional patient specific information related to health status or need. We included randomised controlled trials, non-randomised controlled trials, interrupted time series (ITS) analyses, repeated measures studies and controlled before-after studies set in large care systems or jurisdictions. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed study limitations. Quantitative re-analysis of time series data was undertaken for studies with sufficient data. MAIN RESULTS: We included 29 ITS analyses (12 were controlled) investigating policies targeting 11 drug classes for restriction. Participants were most often senior citizens or low income adult populations, or both, in publically subsidized or administered pharmaceutical benefit plans. Impact of policies varied by drug class and whether restrictions were implemented or relaxed. When policies targeted gastric-acid suppressant and non-steroidal anti-inflammatory drug classes, decreased drug use and substantial savings on drugs occurred immediately and for up to two years afterwards, with no increase in the use of other health services (6 studies). Targeting second generation antipsychotic drugs increased treatment discontinuity and the use of other health services without reducing overall drug expenditures (2 studies). Relaxing restrictions for reimbursement of antihypertensives and statins increased appropriate use and decreased overall drug expenditures. Two studies which measured health outcomes directly were inconclusive. AUTHORS' CONCLUSIONS: Implementing restrictions to coverage and reimbursement of selected medications can decrease third-party drug spending without increasing the use of other health services (6 studies). Relaxing reimbursement rules for drugs used for secondary prevention can also remove barriers to access. Policy design, however, needs to be based on research quantifying the harm and benefit profiles of target and alternative drugs to avoid unwanted health system and health effects. Health impact evaluation should be conducted where drugs are not interchangeable. Impacts on health equity, relating to the fair and just distribution of health benefits in society (sustainable access to publically financed drug benefits for seniors and low income populations, for example), also require explicit measurement.

Recruitment to publicly funded trials--are surgical trials really different?

BACKGROUND: Good recruitment is integral to the conduct of a high-quality randomised controlled trial. It has been suggested that recruitment is particularly difficult for evaluations of surgical interventions, a field in which there is a dearth of evidence from randomised comparisons. While there is anecdotal speculation to support the inference that recruitment to surgical trials is more challenging than for medical trials we are unaware of any formal assessment of this. In this paper, we compare recruitment to surgical and medical trials using a cohort of publicly funded trials. DATA: Overall recruitment to trials was assessed using of a cohort of publicly funded trials (n=114). Comparisons were made by using the Recruitment Index, a simple measure of recruitment activity for multicentre randomised controlled trials. Recruitment at the centre level was also investigated through three example surgical trials. RESULTS: The Recruitment Index was found to be higher, though not statistically significantly, in the surgical group (n=18, median=38.0 IQR (10.7, 77.4)) versus (n=81, median=34.8 IQR (11.7, 98.0)) days per recruit for the medical group (median difference 1.7 (-19.2, 25.1); p=0.828). For the trials where the comparison was between a surgical and a medical intervention, the Recruitment Index was substantially higher (n=6, 68.3 (23.5, 294.8)) versus (n=93, 34.6 (11.7, 90.0); median difference 25.9 (-35.5, 221.8); p=0.291) for the other trials. CONCLUSIONS: There was no clear evidence that surgical trials differ from medical trials in terms of recruitment activity. There was, however, support for the inference that medical versus surgical trials are more difficult to recruit to. Formal exploration of the recruitment data through a modelling approach may go some way to tease out where important differences exist.