Use of re-randomized data in meta-analysis

BACKGROUND: Outcomes collected in randomized clinical trials are observations of random variables that should be independent and identically distributed. However, in some trials, the patients are randomized more than once thus violating both of these assumptions. The probability of an event is not always the same when a patient is re-randomized; there is probably a non-zero covariance coming from observations on the same patient. This is of particular importance to the meta-analysts. METHODS: We developed a method to estimate the relative error in the risk differences with and without re-randomization of the patients. The relative error can be estimated by an expression depending on the percentage of the patients who were re-randomized, multipliers (how many times more likely it is to repeat an event) for the probability of reoccurrences, and the ratio of the total events reported and the initial number of patients entering the trial. RESULTS: We illustrate our methods using two randomized trials testing growth factors in febrile neutropenia. We showed that under some circumstances the relative error of taking into account re-randomized patients was sufficiently small to allow using the results in the meta-analysis. Our findings indicate that if the study in question is of similar size to other studies included in the meta-analysis, the error introduced by re-randomization will only minimally affect meta-analytic summary point estimate. We also show that in our model the risk ratio remains constant during the re-randomization, and therefore, if a meta-analyst is concerned about the effect of re-randomization on the meta-analysis, one way to sidestep the issue and still obtain reliable results is to use risk ratio as the measure of interest. CONCLUSION: Our method should be helpful in the understanding of the results of clinical trials and particularly helpful to the meta-analysts to assess if re-randomized patient data can be used in their analyses

Lymphoma incidence, survival and prevalence 2004–2014 : sub-type analyses from the UK’s Haematological Malignancy Research Network

Background: Population-based information about cancer occurrence and survival are required to inform clinical practice and research; but for most lymphomas data are lacking. Methods: Set within a socio-demographically representative UK population of nearly 4 million, lymphoma data (N ¼ 5796) are from an established patient cohort. Results: Incidence, survival (overall and relative) and prevalence estimates for 420 subtypes are presented. With few exceptions, males tended to be diagnosed at younger ages and have significantly (Po0.05) higher incidence rates. Differences were greatest at younger ages: the o15 year male/female rate ratio for all subtypes combined being 2.2 (95% CI 1.3–3.4). These gender differences impacted on prevalence; most subtype estimates being significantly (Po0.05) higher in males than females. Outcome varied widely by subtype; survival of patients with nodular lymphocyte predominant Hodgkin lymphoma approached that of the general population, whereas less than a third of those with other B-cell (e.g., mantle cell) or T-cell (e.g., peripheral-T) lymphomas survived for Z5 years. No males/female survival differences were detected. Conclusions: Major strengths of our study include completeness of ascertainment, world-class diagnostics and generalisability. The marked variations demonstrated confirm the requirement for ‘real-world’ data to inform aetiological hypotheses, health-care planning and the future monitoring of therapeutic changes

A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients.

Contains fulltext : 48842.pdf (publisher's version ) (Closed access)We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications

Clinicians' attitudes towards clinical trials of cancer therapy

Background:Patient accrual into cancer clinical trials remains at low levels. This survey elicited attitudes and practices of cancer clinicians towards clinical trials. Method:The 43-item Clinicians Attitudes to Clinical Trials Questionnaire was completed by participants in an intervention study aimed at improving multi-disciplinary involvement in randomised trials. Responses from 13 items were summed to form a research-orientation score. Results:Eighty-seven clinicians (78%) returned questionnaires. Physicians, more often than surgeons, chose to prioritise prolonging a patient's life, recruited 50% of patients into trials and attended more research-focussed conferences. Clinicians at specialist centres were more positive about trials with no-treatment arms than those at district general hospitals, more likely to believe clinician, rather than patient reluctance to participate was the greater obstacle to trial accrual, and preferred national and international to local recognition. Clinicians belonging to breast and colorectal teams were less disappointed about not enrolling patients in trials and more accepting of no-treatment arm trials. Research orientation was higher in physicians than surgeons and higher in specialist centres than district hospitals. Conclusions:This study provides greater understanding of clinicians’ attitudes to trials. Results have been used to inform training interventions for clinicians targeting the problem of low and selective accrual

A patient-reported outcome instrument to assess the impact of oropharyngeal mucositis on health-related quality of life: a longitudinal psychometric evaluation

Goals of work: An oropharyngeal mucositis (OM)-specific health-related quality of life measure (OMQoL) has been developed to assess the impact of OM from the perspective of patients. The current paper describes the convergent, concurrent, and known-group validities and responsiveness in relation to clinical and health outcomes. Materials and methods: A multicenter approach was used, and 137 patients treated with different cancer therapies completed the OMQoL and the European Organization for Research and Treatment of Cancer Quality of Life questionnaire [EORTC QLQ-C30 (Ch)] twice over a 4-week period or weekly over a 7-week period, along with concurrent measures of OM and its related symptoms. Main results: The OM-related symptom scores correlated highly with the OMQoL, confirming its convergent validity (r∈=∈-0.724 - 0.971, p∈<∈0.01). Moderate correlations between the subscales of the OMQoL and EORTC QLQ-C30 (Ch) were indicative of good concurrent validity (r∈=∈0.450-0.724, p∈<∈0.01). The OMQoL was able to distinguish between patients with different severities of OM (p∈<∈0.01) and types of cancer therapy (p∈<∈0.01), providing evidence of good known-group validity. The changes in effects sizes corresponding to changes in OM curves indicate that the OMQoL is responsive to changes in OM status. Conclusions: These findings suggest that the OMQoL has very good psychometric properties and can be used as a health-related quality of life assessment for cancer patients with OM. Much work is still needed in strengthening the psychometric qualities and interpretability of the OMQoL by demonstrating its ability to detect outcome changes over time. © 2008 Springer-Verlag.link_to_subscribed_fulltex