Clare Bradley

Patient preferences and randomised clinical trials.

The child should be examined but not without the knowledge and agreement of a parent (or the order of a court). Mothers of pr?adolescent children should always be invited to be present, except in the most exceptional circumstances. Adolescent patients should be asked whether they wish a parent to be present. It is usually counterproductive to examine a resistant child, and if his or her cooperation cannot be obtained the examination should be deferred unless there are urgent medical reasons to proceed. The child should be examined as soon as optimal arrangements can be made. Few children require urgent examination. Repetitive examination is usually abusive and should be avoided. The examination should be conducted in absolute privacy and in an environment where the child can be comfortable?not behind screens in open wards or in police stations. There should be adequate equipment for any necessary diagnostic tests. Recording and photographic facilities are an advantage but their value is outweighed if they cause distress to the child or mean that another examination has to be conducted. Who should examine?

Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial.

BACKGROUND As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic control in adults with inadequately controlled type 2 diabetes mellitus taking oral hypoglycaemic agents. METHODS In the 44-week, parallel, open study that was undertaken in 69 study sites across Europe and Australia, 418 patients with type 2 diabetes mellitus that was inadequately controlled by oral hypoglycaemic agents were randomly assigned to either insulin glargine taken once daily at the same time every day or to insulin lispro administered three times per day. The primary objective was to compare the change in haemoglobin A(1c) from baseline to endpoint (week 44) between the two regimens. Randomisation was done with a central randomisation service. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00311818. FINDINGS 205 patients were randomly assigned to insulin glargine and 210 to insulin lispro. Mean haemoglobin A(1c) decrease in the insulin glargine group was -1.7% (from 8.7% [SD 1.0] to 7.0% [0.7]) and -1.9% in the insulin lispro group (from 8.7% [1.0] to 6.8% [0.9]), which was within the predefined limit of 0.4% for non-inferiority (difference=0.157; 95% Cl -0.008 to 0.322). 106 (57%) patients reached haemoglobin A(1c) of 7% or less in the glargine group and 131 (69%) in the lispro group. In the glargine group, the fall in mean fasting blood glucose (-4.3 [SD 2.3] mmol/L vs -1.8 [2.3] mmol/L; p<0.0001) and nocturnal blood glucose (-3.3 [2.8] mmol/L vs -2.6 [2.9] mmol/L; p=0.0041) was better than it was in the insulin lispro group, whereas insulin lispro better controlled postprandial blood glucose throughout the day (p<0.0001). The incidence of hypoglycaemic events was less with insulin glargine than with lispro (5.2 [95% CI 1.9-8.9] vs 24.0 [21-28] events per patient per year; p<0.0001). Respective mean weight gains were 3.01 (SD 4.33) kg and 3.54 (4.48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3.13; 95% CI 2.04-4.22). INTERPRETATION A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A(1c). We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro. FUNDING Sanofi-Aventis.

Measures of psychological well-being and treatment satisfaction developed from the responses of people with tablet-treated diabetes.

Psychological outcome measures of Well‐being and Treatment Satisfaction have been designed and developed for people with tablet‐treated Type 2 diabetes. The Well‐being scale includes three six‐item sub‐scales to measure Depression, Anxiety, and Positive Well‐being. A prime consideration when selecting items for the psychological well‐being measures was to minimize the confounding of diabetic symptomatology with the somatic symptoms of depression and anxiety. Cronbachs alpha indicated that each of the Well‐being sub‐scales and the Treatment Satisfaction scale was internally reliable (alphas ranged from 0.70 to 0.88) and evidence for construct validity was provided by predicted associations with other variables collected at the time of the study. For example, lower Well‐being scores were associated with being overweight (Depression: p < 0.05; Anxiety: p < 0.001) while greater Satisfaction with Treatment was associated with lower HbA1 levels (p < 0.001) and lower percent ideal body weight (p < 0.01). These scales should prove particularly useful where measures of quality of life are required to complement metabolic variables when evaluating new treatments, education programmes, and other interventions, or in the routine auditing of established methods of treatment.

Importance of differentiating health status from quality of life

Of nine exhibits in the Quality of Life with Diabetes poster event at the recent European Association for the Study of Diabetes meeting in Jerusalem, five used measures of health status (EQ5D and SF-36) and two others used measures of well-being (W-BQ22). All nine referred to the measures used as quality-of-life measures. The EQ5D and SF-36 measure how people feel about their health (physical and mental) and the W-BQ22 measures feelings of depression, anxiety, energy, and positive well-being. If people feel that their health or well-being is poor, they may feel that their quality of life is also impaired, though this is not necessarily the case. The opposite – that just because they feel that their health is excellent and they are not depressed or anxious, their quality of life is excellent – may not be true either.

Treatment satisfaction and psychological well-being with insulin glargine compared with NPH in patients with Type 1 diabetes.

Aims  To assess satisfaction with treatment and psychological well‐being associated with insulin glargine and Neutral Protamine Hagedorn (NPH). Insulin glargine, a new long‐acting insulin analogue, provides constant, peakless insulin release following once‐daily administration and is associated with fewer hypoglycaemic episodes, despite metabolic control equivalent to that achieved with NPH human basal insulin.

Risk of diabetes in offspring of parents with non-insulin-dependent diabetes.

Diabetes mellitus affects about 2% of Western European populations and represents a lifetime risk of 10-1 5%. It i s by far the commonest endocrine disorder and its incidence and prevalence are increasing.’ Current ideas about the pathogenesis of non-insulin dependent (type 2) diabetes (NIDDM) increasingly encourage calls for preventive action.24 Such action inevitably requires an evaluation of risk status for the disease. There are two main primary preventive strategies: a ’general population’ approach and a ’high risk’ approach. The former consists of the non-selective application of preventive measures across the whole population to reduce the risk factors for NIDDM, for example, by avoiding obesity, promoting normal body weight and by encouraging more physically active lifestyles. The ’high risk’ strategy concentrates preventive activity on people defined as being at particularly high risk. If this latter strategy is adopted, it is important to identify which people are specially vulnerable, and to have estimates of the magnitude of their enhanced risk. This review concerns itself with one readily identifiable high-risk group: people with a positive parental history of NIDDM. A number of factors, both genetic and environmental, influence the offspring’s risk of developing NIDDM. Factors affecting the individual’s genetic endowment include family history, type of diabetes involved, whether one or both of the parents have diabetes, and race. Risk of disease expression i s also related to lifestyle factors, the most important of which are probably obesity5 and physical inactivity.” The roles of intrauterine and early life environment factors have been emphasized recently by the work of Hales, Barker and colleagues on the predictive relationship between low foetal and infant growth rates and impaired glucose tolerance in later life.’

Long-term biomedical and psychosocial outcomes following DAFNE (Dose Adjustment For Normal Eating) structured education to promote intensive insulin therapy in adults with sub-optimally controlled Type 1 diabetes

AIMS To explore long-term outcomes of participation in a Dose Adjustment For Normal Eating (DAFNE) training course, which provided one-off exposure to structured education in intensive insulin therapy to people with established Type 1 diabetes. METHODS A cohort design follow-up of original trial participants at a mean of 44 months (range: 37-51 months) in hospital diabetes clinics in three English health districts. 104 (74%) original participants provided biomedical data; 88 (63%) completed questionnaires including the ADDQoL, measuring impact of diabetes on quality of life (QoL). RESULTS At 44 months, mean improvement in HbA(1c) from baseline was 0.36% (9.32+/-1.1% to 8.96+/-1.2%, p<0.01) remaining significant but deteriorated from 12 months (p<0.05). Improvements in QoL seen at 12 months were sustained at 44 (e.g. impact of diabetes on dietary freedom: -1.78+/-2.33 at 44 months versus -4.27+/-2.94, baseline, p<0.0001; versus 1.80+/-2.32 at 12 months, ns). Similar results were obtained using last observation carried forward for patients not supplying follow-up data. CONCLUSIONS The impact of a single DAFNE course on glycaemic control remains apparent in the long term, although further interventions will be required to achieve recommended HbA(1c). In contrast, improvements in QoL and other patient-reported outcomes are well maintained over approximately 4 years.

Development of scales to measure perceived control of diabetes mellitus and diabetes-related health beliefs.

A series of scales was designed to measure perceived control of diabetes and diabetes‐related health beliefs with a view to predicting treatment preferences and individual differences in response to the treatments. Scale development is described and the psychometric properties examined with responses from 286 insulin requiring adult diabetic patients. Patients were significantly more likely (p < 0.001) to attribute responsibility for their diabetes control to themselves rather than to their medical advisors or to other factors.

The ADKnowl: identifying knowledge deficits in diabetes care

Aims  To present the ADKnowl measure of diabetes‐related knowledge and evaluate its use in identifying the nature and extent of patient and health professional knowledge deficits.

Designing Medical and Educational Intervention Studies: A review of some alternatives to conventional randomized controlled trials

The advantages and limitations of RCT designs are discussed, and a range of alternative designs for medical and educational intervention studies considered. Designs selected are those that address the much neglected psychological issues involved in the recruitment of patients and allocation of patients to treatments within trials. Designs include Zelens (18) randomized consent design, Brewin and Bradleys (20) partially randomized patient-centered design, and Korn and Baumrinds (21) partially randomized clinician-centered design. The possibilities of combining features from each of the last two designs are illustrated, and the advantages of adopting a more flexible and clinically relevant approach to the design of clinical trials are discussed.