Sample Size Considerations for GEE Analyses of Three-Level Cluster Randomized Trials

Cluster randomized trials in health care may involve three instead of two levels, for instance, in trials where different interventions to improve quality of care are compared. In such trials, the intervention is implemented in health care units (“clusters”) and aims at changing the behavior of health care professionals working in this unit (“subjects”), while the effects are measured at the patient level (“evaluations”). Within the generalized estimating equations (GEE) approach, we derive a sample size formula that accounts for two levels of clustering: that of subjects within clusters and that of evaluations within subjects. The formula reveals that sample size is inflated, relative to a design with completely independent evaluations, by a multiplicative term that can be expressed as a product of two variance inflation factors, one that quantifies the impact of within-subject correlation of evaluations on the variance of subject-level means and the other that quantifies the impact of the correlation between subject level means on the variance of the cluster means. Power levels as predicted by the sample size formula agreed well with the simulated power for more than 10 clusters in total, when data was analyzed using bias-corrected estimating equations for the correlation parameters in combination with the model-based covariance estimator or the sandwich estimator with a finite sample correction

The design of the Dutch EASYcare study: a randomised controlled trial on the effectiveness of a problem-based community intervention model for frail elderly people [NCT00105378]

BACKGROUND: Because of their complex clinical presentations and needs frail elderly people require another approach than people who age without many complications. Several inpatient geriatric health services have proven effectiveness in frail persons. However, the wish to live independently and policies that promote independent living as an answer to population aging call for community intervention models for frail elderly people. Maybe models such as preventive home visits, comprehensive geriatric assessment, and intermediate care qualify, but their efficacy is controversial, especially in frail elderly persons living in the community. With the Dutch EASYcare Study Geriatric Intervention Programme (DGIP) we developed a model to study effectiveness of problem based community intervention models in frail elderly people. METHODS/DESIGN: DGIP is a community intervention model for frail elderly persons where the GP refers elderly patients with a problem in cognition, mood, behaviour, mobility, and nutrition. A geriatric specialist nurse applies a guideline-based intervention with a limited number of follow up visits. The intervention starts with the application of the EASYcare instrument for geriatric screening. The EASYcare instrument assesses (instrumental) activities of daily life, cognition, mood, and includes a goal setting item. During the intervention the nurse regularly consults the referring GP and a geriatrician. Effects on functional performance (Groningen Activity Restriction Scale), health related quality of life (MOS-20), and carer burden (Zarit Burden Interview) are studied in an observer blinded randomised controlled trial. 151 participants were randomised over two treatment arms – DGIP and regular care – using pseudo cluster randomisation. We are currently performing the follow up visits. These visits are planned three and six months after inclusion. Process measures and cost measures will be recorded. Intention to treat analyses will focus on post intervention differences between treatment groups. DISCUSSION: The design of a trial evaluating the effects of a community intervention model for frail elderly people was presented. The problem-based participant selection procedure satisfied; few patients that the GP referred did not meet our eligibility criteria. The use of standard terminology makes detailed insight into the contents of our intervention possible using terminology others can understand well

Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study

Abstract Various signs on routine brain MRI can help differentiate between Parkinson's disease (PD) and the various forms of atypical parkinsonism (AP). Here, we evaluate what routine brain MRI contributes to the clinical diagnosis, in both early and advanced disease stages. We performed a prospective observational study in 113 patients with parkinsonism, but without definite diagnosis upon inclusion. At baseline, patients received a structured interview, comprehensive and standardized neurological assessment, and brain MRI. The silver standard diagnosis was made after 3 years of follow-up (PD n = 43, AP n = 57), which was based on disease progression, repeat standardized neurological examination and response to treatment. The clinical diagnosis was classified as having either 'low certainty' (lower than 80%) or 'high certainty' (80% or higher). The added diagnostic yield of baseline MRI results were then studied relative to clinical neurological evaluation at presentation, and at follow-up. Sensitivity and specificity for separating AP from PD were calculated for all potentially distinguishing MRI abnormalities described previously in the literature. MRI abnormalities showed moderate to high specificity but limited sensitivity for the diagnosis of AP. These MRI abnormalities contributed little over and above the clinically based diagnosis, except when the clinical diagnosis was uncertain. For these patients, presence of putaminal or cerebellar atrophy was particularly indicative of AP. Routine brain MRI has limited added value for differentiating between PD and AP when clinical certainty is already high, but has some diagnostic value when the clinical diagnosis is still uncertain

The effect of the SAFE or SORRY? programme on patient safety knowledge of nurses in hospitals and nursing homes: a cluster randomised trial

Background: patients in hospitals and nursing homes are at risk for the development of often preventable adverse events. Guidelines for the prevention of many types of adverse events are available, however compliance with these guidelines appears to be lacking. As a result many patients do not receive appropriate care. We developed a patient safety program that allows organisations to implement multiple guidelines simultaneously and therefore facilitates guideline use to improve patient safety. This program was developed for three frequently occurring nursing care related adverse events: pressure ulcers, urinary tract infections and falls. For the implementation of this program we developed educational activities for nurses as a main implementation strategy.Objectives: the aim of this study is to describe the effect of interactive and tailored education on the knowledge levels of nurses.Design: a cluster randomised trial was conducted between September 2006 and July 2008.Settings: ten hospital wards and ten nursing home wards participated in this study. Prior to baseline, randomisation of the wards to an intervention or control group was stratified for centre and type of ward.Participants: all nurses from participating wards.Methods: a knowledge test measured nurses’ knowledge on the prevention of pressure ulcers, urinary tract infections and falls, during baseline en follow-up. The results were analysed for hospitals and nursing homes separately.Results: after correction for baseline, the mean difference between the intervention and the control group on hospital nurses’ knowledge on the prevention of the three adverse events was 0.19 points on a zero to ten scale (95% CI: ?0.03 to 0.42), in favour of the intervention group. There was a statistically significant effect on knowledge of pressure ulcers, with an improved mean mark of 0.45 points (95% CI: 0.10–0.81). For the other two topics there was no statistically significant effect. Nursing home nurses’ knowledge did neither improve (0 points, CI: ?0.35 to 0.35) overall, nor for the separate subjects.Conclusion: the educational intervention improved hospital nurses’ knowledge on the prevention of pressure ulcers only. More research on long term improvement of knowledge is neede

Surgical outcome after spinal fractures in patients with ankylosing spondylitis

<p>Abstract</p> <p>Background</p> <p>Ankylosing spondylitis is a rheumatic disease in which spinal and sacroiliac joints are mainly affected. There is a gradual bone formation in the spinal ligaments and ankylosis of the spinal diarthroses which lead to stiffness of the spine.</p> <p>The diffuse paraspinal ossification and inflammatory osteitis of advanced Ankylosing spondylitis creates a fused, brittle spine that is susceptible to fracture. The aim of this study is to present the surgical experience of spinal fractures occurring in patients suffering from ankylosing spondylitis and to highlight the difficulties that exist as far as both diagnosis and surgical management are concerned.</p> <p>Methods</p> <p>Twenty patients suffering from ankylosing spondylitis were operated due to a spinal fracture. The fracture was located at the cervical spine in 7 cases, at the thoracic spine in 9, at the thoracolumbar junction in 3 and at the lumbar spine in one case. Neurological defects were revealed in 10 patients. In four of them, neurological signs were progressively developed after a time period of 4 to 15 days. The initial radiological study was negative for a spinal fracture in twelve patients. Every patient was assessed at the time of admission and daily until the day of surgery, then postoperatively upon discharge.</p> <p>Results</p> <p>Combined anterior and posterior approaches were performed in three patients with only posterior approaches performed on the rest. Spinal fusion was seen in 100% of the cases. No intra-operative complications occurred. There was one case in which superficial wound inflammation occurred. Loosening of posterior screws without loss of stability appeared in two patients with cervical injuries.</p> <p>Frankel neurological classification was used in order to evaluate the neurological status of the patients. There was statistically significant improvement of Frankel neurological classification between the preoperative and postoperative evaluation. 35% of patients showed improvement due to the operation performed.</p> <p>Conclusion</p> <p>The operative treatment of these injuries is useful and effective. It usually succeeds the improvement of the patients' neurological status. Taking into consideration the cardiovascular problems that these patients have, anterior and posterior stabilization aren't always possible. In these cases, posterior approach can be performed and give excellent results, while total operation time, blood loss and other possible complications are decreased.</p

Design and baseline characteristics of the ParkFit study, a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients

<p>Abstract</p> <p>Background</p> <p>Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.</p> <p>Methods</p> <p>We developed the ParkFit Program: a PD-specific and multifaceted behavioral program to promote physical activity. The emphasis is on creating a behavioral change, using a combination of accepted behavioral motivation techniques. In addition, we designed a multicentre randomized clinical trial to investigate whether this ParkFit Program increases physical activity levels over two years in sedentary PD patients. We intended to include 700 sedentary patients. Primary endpoint is the time spent on physical activities per week, which will be measured every six months using an interview-based 7-day recall.</p> <p>Results</p> <p>In total 3453 PD patients were invited to participate. Ultimately, 586 patients - with a mean (SD) age of 64.1 (7.6) years and disease duration of 5.3 (4.5) years - entered the study. Study participants were younger, had a shorter disease duration and were less sedentary compared with eligible PD patients not willing to participate.</p> <p>Discussion</p> <p>The ParkFit trial is expected to yield important new evidence about behavioral interventions to promote physical activity in sedentary patients with PD. The results of the trial are expected in 2012.</p> <p>Trial registration</p> <p><url>http://clinicaltrials.gov</url> (nr NCT00748488).</p

Incorporating natural variation into IVF clinic league tables.

Contains fulltext : 53074.pdf (publisher's version ) (Closed access)BACKGROUND: More and more league tables are being published every day to rate the performance of health boards, hospitals and surgeons. However, they do not show the magnitude of uncertainty caused by natural variation. METHODS: We propose a new method to present league tables in which the ratings are easy to interpret. Instead of just giving one score, we suggest the addition of best-case scenario and worst-case scenario scores. The true performance of a clinic, accounting for natural variation, is most likely to be between the best-case scenario and the worst-case scenario for its rating. These ratings can be computed easily, without any special software. RESULTS: We illustrate our method based on data of Dutch IVF clinics from 2004. Six (out of 13) clinics shared a 'top of the league' position when considering the best-case scenario. CONCLUSION: There is great uncertainty about the ratings. To show the magnitude of uncertainty, league tables should include the best-case scenario and the worst-case scenario ratings of each clinic

An investigation of clinical studies suggests those with multiple objectives should have at least 90% power for each endpoint.

BACKGROUND AND OBJECTIVES: Many clinical studies have more than one objective, either formally or informally, but this is not usually taken into account in the determination of the sample size. We investigated the overall power of a study, that is, the probability that all the objectives will be met. METHODS: We calculated the overall power in the case that the study has two primary outcome variables and in the case that one outcome variable is evaluated on two subsets, in particular, the Per Protocol group and the Intention to Treat group. RESULTS: A power of 80% for each of the two end points leads to poor power for the end points combined. However, a power of 90% preserves better the overall power. The power of the Per Protocol analysis can be higher or lower than the power of the Intention to Treat analysis. CONCLUSION: Power should be calculated for all end points combined, and it should be at least 90% for each primary end point. If the sample size for the intention-to-treat analysis is determined by adding a percentage of "nonevaluable subjects" to the sample size required for the per protocol analysis, then this may lead to an underpowered study

Small studies are more heterogeneous than large ones: a meta-meta-analysis

AbstractObjectivesBetween-study heterogeneity plays an important role in random-effects models for meta-analysis. Most clinical trials are small, and small trials are often associated with larger effect sizes. We empirically evaluated whether there is also a relationship between trial size and heterogeneity (τ).Study Design and SettingWe selected the first meta-analysis per intervention review of the Cochrane Database of Systematic Reviews Issues 2009–2013 with a dichotomous (n = 2,009) or continuous (n = 1,254) outcome. The association between estimated τ and trial size was evaluated across meta-analyses using regression and within meta-analyses using a Bayesian approach. Small trials were predefined as those having standard errors (SEs) over 0.2 standardized effects.ResultsMost meta-analyses were based on few (median 4) trials. Within the same meta-analysis, the small study τS2 was larger than the large-study τL2 [average ratio 2.11; 95% credible interval (1.05, 3.87) for dichotomous and 3.11 (2.00, 4.78) for continuous meta-analyses]. The imprecision of τS was larger than of τL: median SE 0.39 vs. 0.20 for dichotomous and 0.22 vs. 0.13 for continuous small-study and large-study meta-analyses.ConclusionHeterogeneity between small studies is larger than between larger studies. The large imprecision with which τ is estimated in a typical small-studies' meta-analysis is another reason for concern, and sensitivity analyses are recommended