Bruno Heleno

Quantification of harms in cancer screening trials: literature review

Objectives To assess how often harm is quantified in randomised trials of cancer screening. Design Two authors independently extracted data on harms from randomised cancer screening trials. Binary outcomes were described as proportions and continuous outcomes with medians and interquartile ranges. Data sources For cancer screening previously assessed in a Cochrane review, we identified trials from their reference lists and updated the search in CENTRAL. For cancer screening not assessed in a Cochrane review, we searched CENTRAL, Medline, and Embase. Eligibility criteria for selecting studies Randomised trials that assessed the efficacy of cancer screening for reducing incidence of cancer, cancer specific mortality, and/or all cause mortality. Data extraction Two reviewers independently assessed articles for eligibility. Two reviewers, who were blinded to the identity of the study’s authors, assessed whether absolute numbers or incidence rates of outcomes related to harm were provided separately for the screening and control groups. The outcomes were false positive findings, overdiagnosis, negative psychosocial consequences, somatic complications, invasive follow-up procedures, all cause mortality, and withdrawals because of adverse events. Results Out of 4590 articles assessed, 198 (57 trials, 10 screening technologies) matched the inclusion criteria. False positive findings were quantified in two of 57 trials (4%, 95% confidence interval 0% to 12%), overdiagnosis in four (7%, 2% to 18%), negative psychosocial consequences in five (9%, 3% to 20%), somatic complications in 11 (19%, 10% to 32%), use of invasive follow-up procedures in 27 (47%, 34% to 61%), all cause mortality in 34 (60%, 46% to 72%), and withdrawals because of adverse effects in one trial (2%, 0% to 11%). The median percentage of space in the results section that reported harms was 12% (interquartile range 2-19%). Conclusions Cancer screening trials seldom quantify the harms of screening. Of the 57 cancer screening trials examined, the most important harms of screening—overdiagnosis and false positive findings—were quantified in only 7% and 4%, respectively.

Healthcare costs in the Danish randomised controlled lung cancer CT-screening trial: a registry study.

OBJECTIVESnLow dose computerised tomography (CT) screening for lung cancer can reduce lung-cancer-specific mortality. The objective of this study was to analyse healthcare costs and healthcare utilisation of participants in the Danish lung cancer CT-screening trial (DLCST).nnnMATERIALS AND METHODSnThis registry study was nested in a randomised controlled trial (DLCST). 4104 participants, current or former heavy smokers, aged 50-70 years were randomised to five annual low dose CT scans or usual care during 2004-2010. Total healthcare costs and healthcare utilisation data for both the primary and the secondary healthcare sector were retrieved from public registries from randomisation - September 2011 and compared between (1) the CT-screening group and the control group and, (2) the control group and each of the true-positive, false-positive and true-negative groups.nnnRESULTSnThe median annual costs per participant were significantly higher in the CT-screening group (Euros [EUR] 1342, interquartile range [IQR] 750-2980) compared with the control group (EUR 1190, IQR 590-2692) (p<0.0001). When the cost of the CT-screening programme was excluded, there was no longer a statistically significant difference between the CT-screening group (EUR 1155, IQR 567-2798) and the control group (p=0.52). Analyses according to the diagnostic groups showed that annual costs were 10.57 (95% CI 7.09-15.75) times higher for the true-positive and 1.67 (95% CI 1.20-2.32) times higher for the false-positive group compared with the control group.nnnCONCLUSIONnLow dose lung cancer CT screening increases healthcare costs compared with no screening; this difference was attributable to the costs of the CT-screening programme. Overall healthcare costs were higher for the true-positive and false-positive groups than for the control group, also when excluding the cost of the CT-screening programme. This increase was outweighed by the larger true-negative group showing no significant differences in costs compared with the control group.

Lung cancer screening with low-dose CT (LDCT), or when a public health intervention is beyond the patient’s benefit

Lung cancer is the main cause of cancer death in the developed world. It is also the second most incident cancer in males and the third in females. Tobacco is its main risk factor, with 90% of all LC deaths attributable to tobacco consumption. It has a 13% 5-year survival,1 and more than 60% of all LCs are diagnosed in advanced stages. To reduce the burden of disease, it would be very important to have a screening test that is able to: (1) detect LC at an early stage to modify its prognosis, (2) present a low percentage of false-positives, to avoid unnecessary harms, (3) minimise adverse effects for the patient (ie, cancer-induced radiation) and (4) be cost-effective for the health system.nnScreening effectiveness is being assessed in randomised trials. There are seven ongoing trials comparing low-dose CT (LDCT) with usual care.2 The only trial which has published final incidence and mortality results is the National Lung Screening Trial (NLST), which compared LDCT versus chest X-ray (CXR).3 The NLST has the highest sample size to date and there are no forthcoming trials with higher sample sizes. It included individuals aged between 55–74u2005years who had smoked at least 30 pack-years, and ex-smokers with less than 15 years since quitting. It found a 20% relative risk reduction in LC mortality and a 6.7% reduction in all-cause mortality. For each 1000 participants in the trial, LDCT avoids 5 deaths of which 3 are due to LC. The NLST was a well-designed study including more than 53u2005000 participants with three screening rounds and an extra follow-up of 5u2005years after the screening stopped.nnThese results have encouraged many scientific societies to recommend LC screening …

Diagnostic Invasiveness and Psychosocial Consequences of False-Positive Mammography

PURPOSE We undertook a study to assess whether women with false-positive mammography have worse psychosocial consequences if managed with a workup that involves a biopsy (invasive group) than if managed with only additional imaging (noninvasive group). METHODS We performed subgroup analysis of a cohort study of 454 women with abnormal screening mammography and 908 matched control women with normal results. Using a condition-specific questionnaire (Consequences of Screening in Breast Cancer), we assessed 12 psychosocial consequences at 5 time points (0, 1, 6, 18, and 36 months after final diagnosis) and compared the 2 groups of women with false-positives (invasive and noninvasive management groups). RESULTS Among the 252 women with false-positive mammography eligible for this study, psychosocial consequences were similar for those managed invasively and those managed noninvasively during the 36 months of follow-up. In 60 comparisons (12 scales and 5 time points), differences between the groups were never statistically significant (P <.01) and the point estimates for the differences were always close to zero. The psychosocial consequences of women with false-positive results, regardless of management, fell between those of women with normal mammography and those of women determined to have breast cancer. CONCLUSIONS We found no evidence that use of more invasive diagnostics was associated with worse psychosocial consequences. It is therefore reasonable to pool subgroups of women with false-positives in a single analysis. The invasiveness of subsequent diagnostic procedures does not help to identify women at higher risk for adverse psychosocial consequences of false-positive mammography.

Waiting time and the psychosocial consequences of false-positive mammography: cohort study

BackgroundThere is wide variation in the psychosocial response to false-positive mammography. We aimed to assess whether women having to wait longer to exclude cancer had increased psychosocial consequences that persisted after cancer was ruled out.FindingsWe selected women with false-positive mammography (nu2009=u2009272), screened for breast cancer in Copenhagen and Funen (Denmark) over a 1-year period. We measured psychosocial consequences immediately before women attended their recall visit and 1, 6, 18 and 36xa0months after women received their final diagnosis. After women were told that cancer had been ruled out, adverse psychosocial consequences decreased with time. We found no statistically significant differences between women who had cancer ruled out immediately at the recall visit (waiting time of 0) and women who had to wait longer before cancer was ruled out (waiting times 1-30, 30-120 andu2009>u2009120xa0days), when psychosocial consequences were measured via a condition-specific questionnaire (Consequences of Screening in Breast Cancer) at 5 time points (0, 1, 6, 18 and 36xa0months after cancer exclusion).ConclusionWe did not confirm that waiting time was associated with worse long-term psychosocial consequences but type II error (failure to detect a true difference) might be a plausible explanation for our results.

An open cluster-randomized, 18-month trial to compare the effectiveness of educational outreach visits with usual guideline dissemination to improve family physician prescribing

BackgroundThe Portuguese National Health Directorate has issued clinical practice guidelines on prescription of anti-inflammatory drugs, acid suppressive therapy, and antiplatelets. However, their effectiveness in changing actual practice is unknown.MethodsThe study will compare the effectiveness of educational outreach visits regarding the improvement of compliance with clinical guidelines in primary care against usual dissemination strategies. A cost-benefit analysis will also be conducted. We will carry out a parallel, open, superiority, randomized trial directed to primary care physicians. Physicians will be recruited and allocated at a cluster-level (primary care unit) by minimization. Data will be analyzed at the physician level. Primary care units will be eligible if they use electronic prescribing and have at least four physicians willing to participate. Physicians in intervention units will be offered individual educational outreach visits (one for each guideline) at their workplace during a six-month period. Physicians in the control group will be offered a single unrelated group training session. Primary outcomes will be the proportion of cyclooxygenase-2 inhibitors prescribed in the anti-inflammatory class, and the proportion of omeprazole in the proton pump inhibitors class at 18 months post-intervention. Prescription data will be collected from the regional pharmacy claims database. We estimated a sample size of 110 physicians in each group, corresponding to 19 clusters with a mean size of 6 physicians. Outcome collection and data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and detailers cannot be blinded.DiscussionThis trial will attempt to address unresolved issues in the literature, namely, long term persistence of effect, the importance of sequential visits in an outreach program, and cost issues. If successful, this trial may be the cornerstone for deploying large scale educational outreach programs within the Portuguese National Health Service.Trial registrationClinicalTrials.gov number NCT01984034.

Quaternary prevention: reviewing the concept

Abstract Background: According to the Wonca International Dictionary for General/Family Practice Quaternary Prevention is defined as: ‘Action taken to identify patient at risk of overmedicalization, to protect him from new medical invasion, and to suggest to him interventions, which are ethically acceptable.’ The concept of quaternary prevention was initially proposed by Marc Jamoulle and the targets were mainly patients with illness but without a disease. Objectives: The purpose of this opinion article is to open the debate around a new possible definition and a new conceptual model of quaternary prevention based on the belief that quaternary prevention should be present in physicians’ minds for every intervention they suggest to a patient. Discussion: The debate around quaternary prevention is vital in the context of contemporary medicine and has expanded worldwide. The human being may suffer harm from medical interventions from conception, during their childhood, during their entire healthy lifetime as well as during a self-limited disease, a chronic disease, or a terminal disease. The current definition of quaternary prevention has limitations because it excludes patients and medical interventions where a quaternary prevention perspective would be needed and useful to protect patients from harm. In this context, a new definition and conceptual model of quaternary prevention is proposed. Conclusion: In this new proposal, quaternary prevention is defined as an ‘action taken to protect individuals (persons/patients) from medical interventions that are likely to cause more harm than good.’

Portuguese primary care physicians response rate in surveys: a systematic review

INTRODUCTIONnSurveys are a useful tool in primary care. However, low response rates can introduce selection bias, impairing both external and internal validity. The aim of this study was to assess the average response rate in surveys with Portuguese general practitioners (GPs).nnnMETHODnWe searched the Medline, Web of Science, Scopus, Embase, PsychInfo, SciELO, IndexRMP, RCAAP, Revista Portuguesa de Medicina Geral e Familiar, Acta Médica Portuguesa and the proceedings of conferences of general practice from incepton to December 2016. We included all postal, e-mail, telephone and personal surveys to primary care physicians without language restrictions. We did not assess risk of bias of included studies, since the main outcome was survey response rate. We performed planned subgroup analyses of the use of monetary incentives, the use of non-monetary incentives, survey delivery modes and prior contact with participants.nnnRESULTSnA total of 1,094 papers were identified and 37 studies were included in this review. The response rate in surveys done to Portuguese GPs was 56% (95CI 47-64%). There was substantial heterogeneity among included studies (I2=99%), but subgroup analysis did not explain this heterogeneity.nnnCONCLUSIONnConsistent with other published studies, the average response rate in surveys done with Portuguese GPs was 56%, with substantial variation among studies. Use of monetary incentives, one of the most effective strategies to increase response rates, was not present in any of the included studies.

Effect of European Medicines Agency's regulatory measures on nimesulide utilization in Portugal

Severe hepatic adverse events led the European Medicines Agency to recommend restrictions on nimesulide use. Our aim was to determine their effect on nimesulide dispensing in Portugal.

Effect of European Medicines Agency's restrictions on trimetazidine utilization in Portugal.

Following safety concerns regarding trimetazidine, the European Medicines Agency (EMA) recommended restrictions on its use. Our objective was to determine the impact of regulatory actions on trimetazidine utilization in Portugal.