Meta-analysis of individual patient data from randomised trials: a review of methods used in practice

Background: Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion. Methods We review 44 IPD meta-analyses published during the years 1999–2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates. Results: Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases. Conclusions: Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.

A score test for binary data with patient non-compliance

A score test is developed for binary clinical trial data, which incorporates patient non-compliance while respecting randomization. It is assumed in this paper that compliance is all-or-nothing, in the sense that a patient either accepts all of the treatment assigned as specified in the protocol, or none of it. Direct analytic comparisons of the adjusted test statistic for both the score test and the likelihood ratio test are made with the corresponding test statistics that adhere to the intention-to-treat principle. It is shown that no gain in power is possible over the intention-to-treat analysis, by adjusting for patient non-compliance. Sample size formulae are derived and simulation studies are used to demonstrate that the sample size approximation holds. Copyright © 2003 John Wiley & Sons, Ltd.

The benefits of providing benefit information in a patient information leaflet

Objective: To examine the effects of providing two different types of written information about medicine benefits in a patient information leaflet (PIL). Setting: Participants were 358 adult volunteers from the general population recruited from a London railway station and central Reading. Method: The study used a controlled empirical methodology in which people were given a hypothetical, but realistic, scenario about visiting their doctor and being prescribed medication. They then read an information leaflet about the medicine that contained neither, one, or both benefit statements, and finally completed a number of Likert rating scales. Outcome measures included perceived satisfaction and helpfulness of the information, effectiveness and appropriateness of the medicine, benefit and risk to health, and intention to comply. Key findings: Both types of benefit information led to significantly higher ratings on all of the measures taken. Conclusions: Provision of a relatively short ‘benefit’ statement can significantly improve people’s judgements and intention to take a medicine. The findings are important and timely as the European Union is currently considering reviewing their regulations to allow for the inclusion of limited non-promotional benefit information in PILs.

Health informatics: improving patient-centred healthcare pathway

Nowadays the use of information and communication technology is becoming prevalent in many aspects of healthcare services from patient registration, to consultation, treatment and pathology tests request. Manual interface techniques have dominated data-capture activities in primary care and secondary care settings for decades. Despites the improvements made in IT, usability issues still remain over the use of I/O devices like the computer keyboard, touch-sensitive screens, light pen and barcodes. Furthermore, clinicians have to use several computer applications when providing healthcare services to patients. One of the problems faced by medical professionals is the lack of data integrity between the different software applications which in turn can hinder the provision of healthcare services tailored to the needs of the patients. The use of digital pen and paper technology integrated with legacy medical systems hold the promise of improving healthcare quality. This paper discusses the issue of data integrity in e-health systems and proposes the modelling of "Smart Forms" via semiotics to potentially improve integrity between legacy systems, making the work of medical professionals easier and improve the quality of care in primary care practices and hospitals.

Impact of Huntington's across the entire disease spectrum: the phases and stages of disease from the patient perspective

Although Huntington's disease (HD) is a neurodegenerative disease characterized by motor, cognitive and behavioural disturbances, there has been little empirical data examining what patients are most concerned about throughout the different stages of disease, which can span many years. Semi-structured face-to-face interviews were individually conducted with 31 people living with different stages of Huntington's, from pre-clinical gene carriers to advanced stage. We examined how often participants raised issues and concerns regarding the impact of Huntington's on everyday life. The Physical/functional theme hardly featured pre-clinically, but was strongly present from Stage 1, rose steadily and peaked at Stage 5. There were no significant changes between stages for the Emotional, Social, and Self themes that all featured across all stages, indicating that these issues were not raised more frequently over the course of the disease. Likewise, the more rarely mentioned Financial and Legal themes also remained similar across stages. However, the Cognitive theme only featured between Stages 1 and 4, and hardly at all pre-clinically and at Stage 5. These findings provide insight into patients' important and unique perspective and have implications for the management and development of interventions across the spectrum of HD stages.

Health-related quality of life in Huntington’s Disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington’s Disease health-related quality of life questionnaire (HDQoL)

Huntington’s disease (HD) is a fatal, neurodegenerative disease for which there is no known cure. Proxy evaluation is relevant for HD as its manifestation might limit the ability of persons to report their health-related quality of life (HrQoL). This study explored patient–proxy ratings of HrQoL of persons at different stages of HD, and examined factors that may affect proxy ratings. A total of 105 patient–proxy pairs completed the Huntington’s disease health-related quality of life questionnaire (HDQoL) and other established HrQoL measures (EQ-5D and SF-12v2). Proxy–patient agreement was assessed in terms of absolute level (mean ratings) and intraclass correlation. Proxies’ ratings were at a similar level to patients’ self-ratings on an overall Summary Score and on most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries Scale, proxies on average rated HrQoL as better than patients’ self-ratings, while on both the Specific Cognitive Scale and Specific Physical and Functional Scale proxies tended to rate HrQoL more poorly than patients themselves. The patient’s disease stage and mental wellbeing (SF-12 Mental Component scale) were the two factors that primarily affected proxy assessment. Proxy scores were strongly correlated with patients’ self-ratings of HrQoL, on the Summary Scale and all Specific Scales. The patient–proxy correlation was lower for patients at moderate stages of HD compared to patients at early and advanced stages. The proxy report version of the HDQoL is a useful complementary tool to self-assessment, and a promising alternative when individual patients with advanced HD are unable to self-report.

General care of the older cancer patient.

With increasing age, there are greater numbers of older people who will be diagnosed with cancer. It must be remembered that such individuals have increased frailty and have a number of geriatric syndromes and conditions particularly pertinent to older age, including incontinence, poor cognition and impaired nutrition. It is often difficult to define the effects of cancer and its treatment or complications, and separate these from the effects of normal ageing and geriatric syndromes. The documentation of poor nutrition and its management must combine knowledge from both geriatric medicine and oncology. Nutrition serves to identify key healthcare professionals who are all essential in any patient at risk or suffering from malnutrition. Incontinence must be actively sought, its cause identified and efforts made to either 'cure' it or, in certain circumstances, 'manage' it. Older patients with cancer are cared for predominantly by older relations and informal care mechanisms and special consideration of their physical and practical needs are paramount. In this area, nurses, doctors, therapists and social workers should work to identify formal and informal mechanisms to support particularly the older carer.