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Nick Freemantle

Publications and source records attributed to Nick Freemantle.

At least 19 recordsLinked to original sources
PubMed2003

Composite outcomes in randomized trials: greater precision but with greater uncertainty?

Composite outcomes, in which multiple end points are combined, are frequently used as primary outcome measures in randomized trials and are often associated with increased statistical efficiency. However, such measures may prove challenging for the interpretation of results. In this article, we examine the use of composite outcomes in major clinical trials, assess the arguments for and against them, and provide guidance on their application and reporting. To assess incidence and quality of reporting, we systematically reviewed the use of composite end points in clinical trials in Annals of Internal Medicine, BMJ, Circulation, Clinical Infectious Diseases, Journal of the American College of Cardiology, JAMA, Lancet, New England Journal of Medicine, and Stroke from 1997 through 2001 using a sensitive search strategy. We selected for review 167 original reports of randomized trials (with a total of 300 276 patients) that included a composite primary outcome that incorporated all-cause mortality. Sixty-three trials (38%) were neutral both for the primary end point and the mortality component. Sixty trials (36%) reported significant results for the primary outcome measure but not for the mortality component. Only 6 trials (4%) were significant for the mortality component but not for the primary composite outcome, whereas 19 trials (11%) were significant for both. Twenty-two trials (13%) were inadequately reported. Our review suggests that reporting of composite outcomes is generally inadequate, implying that the results apply to the individual components of the composite outcome rather than only to the overall composite. Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials.

Data Interpretation, Statistical↗
PubMed2003

A role for two-stage pharmacoeconomic appraisal? Is there a role for interim approval of a drug for reimbursement based on modelling studies with subsequent full approval using phase III data?

Healthcare decision makers and pharmaceutical companies are increasingly using techniques of economic evaluation, particularly modelling, to assist them in their decisions about drug purchasing and drug development. The use of models in other types of policy decisions is also well established. One option, to shorten the time to a purchasing decision, would be for an interim decision for approval for reimbursement to be based on an economic model. Such a system would mainly benefit the drug development process and thus the pharmaceutical industry; however the approach could also lead to poor decision making, unethical marketing and withdrawal of drugs from the consumer. In this article, we consider the option of a two-stage economic appraisal process from the point of view of the seller, the purchaser and the patient and public. Although a two-stage process may offer some advantages in terms of early return on investment and access, there are significant disadvantages in terms of certainty about effects and public policy and expenditure. Until there are better methods of predicting the effectiveness of a new product, it is unlikely that interim decisions can be seen as a reasonable health policy alternative, although it seems likely that industry may continue to lobby for such an approach.

Australia↗
PubMed2003

Specialist nurse-led intervention to treat and control hypertension and hyperlipidemia in diabetes (SPLINT): a randomized controlled trial.

OBJECTIVE: To determine the effectiveness of specialist nurse-led clinics for hypertension and hyperlipidemia provided for diabetic patients receiving hospital-based care. RESEARCH DESIGN AND METHODS: This study was a randomized controlled implementation trial at Hope Hospital, Salford, U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure(>or=140/80 mmHg), raised total cholesterol (>or=5.0 mmol/l), or both. Individuals with diabetes were randomized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics. Nurses provided clinics for participants, with attendance every 4-6 weeks, until targets were achieved. Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines. Patients with both conditions were eligible for enrollment in either or both clinics. At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register. Data relating to deaths were obtained from the national strategic tracing service. The primary outcome was the odds ratio of achieving targets in hypertension and hyperlipidemia, attributable to the specialist nurse-led intervention. RESULTS: Overall, specialist nurse-led clinics were associated with a significant improvement in patients achieving the target after 1 year (odds ratio [OR] 1.37 [95% CI 1.11-1.69], P = 0.003). This primary analysis revealed a borderline difference in effect between the two types of clinics (test for interaction between groups: P = 0.06). Secondary analysis, consistent with the prior beliefs of the health care professionals involved, suggested that targets were achieved more frequently in patients enrolled in the specialist nurse-led clinic for hyperlipidemia (OR 1.69 [1.25-2.29], P = 0.0007) than for hypertension (OR 1.14 [0.86-1.51], P = 0.37). Intervention (enrolled to either or both clinics) was associated with a reduction in all-cause mortality (OR 0.55 [0.32-0.92], P = 0.02). CONCLUSIONS: This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of patients with diabetes. If the standards of care recommended in the National Service Framework for Diabetes are to be achieved, then such proven methods for delivering care must be adopted.

Aged↗
PubMed2002

The effectiveness and relative effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in patients with heart failure-a meta-regression analysis.

AIMS: To review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure. METHODS: Studies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non-treatment control, were identified. Drugs of the following classes were included, the beta-agonists; dobutamine, high-dose (>2.5 microg/kg/min) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context. RESULTS: With few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CI=0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta-agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data. CONCLUSIONS: Intravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials.

Adrenergic beta-Agonists↗
PubMed2002

Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis.

BACKGROUND: In individual studies and limited meta-analyses venlafaxine has been reported to be more effective than comparator antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). AIMS: To perform a systematic review of all such studies. METHOD: We conducted a systematic review of double-blind, randomised trials comparing venlafaxine with alternative antidepressants in the treatment of depression. The primary outcome was the difference in final depression rating scale value, expressed as a standardised effect size. Secondary outcomes were response rate, remission rate and tolerability. RESULTS: A total of 32 randomised trials were included. Venlafaxine was more effective than other antidepressants (standardised effect size was -0.14, 95% Cl -0.07 to -0.22). A similar significant advantage was found against SSRIs (20 studies) but not tricyclic antidepressants (7 studies). CONCLUSIONS: Venlafaxine has greater efficacy than SSRIs although there is uncertainty in comparison with other antidepressants. Further studies are required to determine the clinical importance of this finding.

Adult↗
PubMed2002

Updating evidence-based clinical guidelines.

OBJECTIVES: To report on the updating of two evidence-based guidelines. METHODS: Development of multi-disciplinary evidence-based guidelines within the North of England Evidence Based Guideline Development Programme. RESULTS: The guideline updating groups were multi-disciplinary although the balance of disciplines was different from the original development groups; the convening of the updating groups allowed refinement of both the skills within the groups and the overall size of the groups. As both groups were starting with a previous version of the guideline, defining the scope of the guideline was more straightforward and faster than when developing the guideline de novo. The process of evidence identification for both guidelines was again by systematic review. Updating the guidelines influenced recommendations in two ways: new evidence required new recommendations; and supplementary evidence in an existing area allowed refinement of recommendations. Overall savings within the guideline updating process (compared with initial development) were modest. The major costs of both the initial guideline development and the updating process were staff costs, which were identical for the two processes. CONCLUSIONS: There is little other experience to set alongside this paper. There is a need for further sharing of experiences and the development of explicit methods for informing decisions on when and how to update evidence-based guidelines.

Adult↗
PubMed2002

Evaluation of a complex intervention for changing professional behaviour: the Evidence Based Out Reach (EBOR) Trial.

OBJECTIVES: To identify the effect of a complex intervention (educational outreach visits by pharmacists) designed to change general practitioners' (GPs') prescribing on each step of a hypothesised pathway of change leading to the final primary trial outcome of change in prescribing. METHOD: The study was undertaken in six health authorities in the North of England and six in London. We described three steps leading to this outcome: the general practices agreeing to participate; GPs in each practice attending the outreach visit conducted by the pharmacists; and the GPs' prescribing practice being influenced by these visits. The outcomes of each step were assessed using a combination of quantitative and qualitative methods. RESULTS: Of the 102 practices randomly selected, 75 (73.5%) agreed to participate. The odds of all the doctors attending the outreach meeting in small practices (i.e. 1-2 partners) was 6.7 (95% CI: 4.4-23.5) compared with other practices (i.e. > 3 partners). Although the pharmacists reported that they had established a good rapport at 100 (72%) first visits and had agreed management plans for 110 (79%) of these visits, they were confident that the practice was likely to alter its prescribing in only 41% of these visits. Pharmacists' and GPs' satisfaction with the outreach visits did not necessarily lead to prescribing changes after the practice visit, and the GPs' knowledge of the guidelines promoted by the pharmacists did not necessarily translate into changes in clinical practice. The main barriers to the implementation of guidelines identified by the pharmacists at the follow-up visits were organisational difficulties, the GPs' scepticism of the evidence presented to them and the doctors' lack of interest in changing their prescribing behaviour. CONCLUSIONS: Although our study is limited by a post hoc rather than a pre hoc design, it provides a pragmatic approach to understanding the factors influencing the pathway of change in prescribing behaviour in response to academic outreach visits.

Cardiovascular Diseases↗
PubMed2002

A randomised controlled trial of the effect of educational outreach by community pharmacists on prescribing in UK general practice.

BACKGROUND: Educational outreach visits are commonly used to promote changes in prescribing in family practice. However, the effectiveness of outreach visits has not been evaluated across a range of settings. AIM: To estimate the effectiveness of educational outreach visits on United Kingdom (UK) general practice prescribing and to examine the extent to which practice characteristics influenced outcome. DESIGN OF STUDY: Randomised controlled trial. SETTING: General practices in 12 health authorities in England. METHOD: Educational outreach visits were made to practices that received two of four guidelines. Each practice provided data on treatment of patients for all four guidelines for both pre and post-intervention periods. The primary outcome is average effect across all four guidelines. Secondary analyses examined the predictive effect of practice and guideline characteristics. RESULTS: Seventy per cent of practices approached agreed to take part in the intervention. Overall, educational outreach was associated with a significant improvement in prescribing practice (odds ratio [OR] = 1.24 [95% CI = 1.07 to 1.42]), a 5.2% (95% CI = 1.7% to 8.7%) increase in the number of patients treated within the guideline recommendations. Smaller practices (two or fewer full-time equivalent practitioners) responded much more favourably to educational outreach than larger practices. Smaller practices improved their performance in line with the guidelines by 13.5% (95% CI = 6% to 20.9%) attributable to outreach, while larger practices improved by only 1.4% (95% CI = -2.4% to 5.3%, P-value for interaction <0.001). CONCLUSION: In large practices, educational outreach alone is unlikely to achieve worthwhile change. There is good evidence to support the use of educational outreach visits in small practices.

Community Pharmacy Services↗
PubMed1999

Incorporating economic analysis in evidence-based guidelines for mental health: the profile approach.

BACKGROUND: Many western health systems are currently developing the role of clinical guidelines to promote effective and efficient health care. However, introducing economic data into guideline methodology designed to assess the effectiveness of interventions raises some methodological issues. These include providing valid and generalizable cost estimates, the weight placed upon cost "evidence" and presenting cost-effectiveness information in a way that is helpful to clinicians. AIM OF THE STUDY: To explore a framework for including economic concepts in the development of a series of primary care guidelines, two of which address mental health conditions. METHODS: A profile approach, setting out best available evidence about the attributes of treatment choices (effectiveness, tolerability, safety, health service delivery, quality of life, resource use and cost), was used to help clinicians to derive treatment recommendations in a manner consistent with both the clinical decision-making process and social objectives. RESULTS: Clinicians involved in guideline development responded well to the process. Although there was often considerable debate about the meaning and importance of different aspects of evidence about treatment, in none of the guideline groups was there failure to agree treatment recommendations. DISCUSSION: The profile approach may be particularly useful in the field of mental health where disease processes may often feature very disparate effects, over long periods of time and impacting upon a broad circle of relatives, carers and agencies in addition to the patients themselves. CONCLUSION: A method has been applied in a series of primary care guidelines, which appears to enable clinicians to consider the issue of resource use alongside the various clinical attributes associated with treatment decisions. The basis of this work is the belief that guidance presenting physical measures describing effectiveness, adverse events, safety, compliance and quality of life, alongside resource consequences, is most likely to appropriately inform doctor-patient interactions. IMPLICATIONS FOR HEALTH CARE PROVISON AND USE: This research may provide a useful platform for other groups considering how to introduce cost-effectiveness concepts into guideline development groups. Whether guidelines change clinical behaviour remains a research question, and the subject of forthcoming trials. IMPLICATIONS FOR HEALTH POLICY FORMULATION: It is important that government agencies realize that guideline development is a health policy tool with prescribed methods to produce valid guidelines. Attempts to tamper with the methodology for cost-containment purposes or other political reasons are likely to discredit a useful mechanism for improving the scientific basis of health care provision. IMPLICATIONS FOR FURTHER RESEARCH: There are a number of limitations to completed work: for example it has a primary care focus and addresses fairly narrowly defined conditions. Work is ongoing to extend the scope to broader disease areas and to secondary care.

Journal Article↗