Issues possibly associated with misinterpreting survival data: A method study.

OBJECTIVE: Proper interpretation of survival data of clinical cancer studies may be difficult and pitfalls related to the nature of Kaplan-Meier analyses might end up in mistaken inferences. The purpose of the present work is to raise awareness of those pitfalls and to prevent errors in future studies. STUDY DESIGN AND SETTING: While evaluating a randomized controlled trial, we came across some issues possibly associated with misinterpreting survival data. We thoroughly reviewed the reporting of survival analyses, statistical approaches, baseline characteristics, and choice of primary end point. The reported data were derived from people with high-risk neuroblastoma. Thus, the trial focused on survival. We reenacted survival functions by deducing the data of various treatment groups from pictured survival functions to estimate the concerning hazard ratios. RESULTS: Opposed to the reporting of the trial, we did not identify a significant difference between treatment groups with respect to overall survival. We were not able to appreciate an effective crossing of survival curves. With respect to event-free survival, we focused on comparable treatment groups and we did not identify a significant difference between treatment groups, thereby again opposing the reporting of the trial. CONCLUSIONS: The present work exemplifies statistical issues that were apparently difficult to detect and that are possibly associated with misinterpreting survival functions. These issues include assumed crossing of survival curves, statistical approach changed in follow-up, different pretreatment between groups, and event-free survival used as primary outcome. Careful handling might prevent similar potential misinterpretation in future studies.

Determinants of a GP visit and cervical cancer screening examination in Great Britain.

OBJECTIVE: In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP. METHODS: A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey. RESULTS: The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination. CONCLUSIONS: Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

Stem cell transplantation of matched sibling donors compared with immunosuppressive therapy for acquired severe aplastic anaemia: a Cochrane systematic review.

OBJECTIVES: Acquired severe aplastic anaemia is a rare and potentially fatal disease. The aim of this Cochrane review was to evaluate the effectiveness and adverse events of first-line allogeneic haematopoietic stem cell transplantation of human leucocyte antigen (HLA)-matched sibling donors compared with first-line immunosuppressive therapy. SETTING: Specialised stem cell transplantations units in primary care hospitals. PARTICIPANTS: We included 302 participants with newly diagnosed acquired severe aplastic anaemia. The age ranged from early childhood to young adulthood. We excluded studies on participants with secondary aplastic anaemia. INTERVENTIONS: We included allogeneic haematopoietic stem cell transplantation as the test intervention harvested from any source of matched sibling donor and serving as a first-line therapy. We included immunosuppressive therapy as comparator with either antithymocyte/antilymphocyte globulin or ciclosporin or a combination of the two. PRIMARY AND SECONDARY OUTCOME MEASURES PLANNED AND FINALLY MEASURED: The primary outcome was overall mortality. Secondary outcomes were treatment-related mortality, graft failure, graft-versus-host disease, no response to immunosuppressive therapy, relapse after initial successful treatment, secondary clonal disease or malignancies, health-related quality of life and performance scores. RESULTS: We identified three prospective non-randomised controlled trials with a study design that was consistent with the principle of 'Mendelian randomisation' in allocating patients to treatment groups. All studies had a high risk of bias due to the study design and were conducted more than 15 years. The pooled HR for overall mortality for the donor group versus the no donor group was 0.95 (95% CI 0.43 to 2.12, p=0.90). CONCLUSIONS: There are insufficient and biased data that do not allow any firm conclusions to be made about the comparative effectiveness of first-line allogeneic haematopoietic stem cell transplantation of HLA-matched sibling donors and first-line immunosuppressive therapy of patients with acquired severe aplastic anaemia.

Failure to address potential bias in non-randomised controlled clinical trials may cause lack of evidence on patient-reported outcomes: a method study.

OBJECTIVES: We conducted a workup of a previously published systematic review and aimed to analyse why most of the identified non-randomised controlled clinical trials with patient-reported outcomes did not match a set of basic quality criteria. SETTING: There were no limits on the level of care and the geographical location. PARTICIPANTS: The review evaluated permanent interstitial low-dose rate brachytherapy in patients with localised prostate cancer and compared that intervention with alternative procedures such as external beam radiotherapy, radical prostatectomy and no primary therapy. PRIMARY OUTCOME MEASURE: Fulfilment of basic inclusion criteria according to a Participants, Interventions, Comparisons, Outcomes (PICO) framework and accomplishment of requirements to contain superimposed risk of bias. RESULTS: We found that 21 of 50 excluded non-randomised controlled trials did not meet the PICO inclusion criteria. The remaining 29 studies showed a lack in the quality of reporting. The resulting flaws included attrition bias due to loss of follow-up, lack of reporting baseline data, potential confounding due to unadjusted data and lack of statistical comparison between groups. CONCLUSIONS: With respect to the reporting of patient-reported outcomes, active efforts are required to improve the quality of reporting in non-randomised controlled trials concerning permanent interstitial low-dose rate brachytherapy in patients with localised prostate cancer.

Changes in the prevalence, treatment and control of hypertension in Germany? A clinical-epidemiological study of 50.000 primary care patients.

INTRODUCTION: Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001. METHODS: Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician's diagnosis of hypertension (HTN(doc)) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician's diagnosis or the patient's self-reported diagnosis of hypertension (HTN(doc,pat)), physician's or patient's self-reported diagnosis or a BP measurement with a systolic BP ≥ 140 mmHg and/or a diastolic BP ≥ 90 (HTN(doc,pat,bp)) and diagnosis according to the National Health and Nutrition Examination Survey (HTN(NHANES)). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined. RESULTS: The overall prevalence rate for hypertension was 35.5% according to HTN(doc) and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity. CONCLUSIONS: Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement.