Results from a blind and a non-blind randomised trial run in parallel: experience from the Estonian Postmenopausal Hormone Therapy (EPHT) Trial

<p>Abstract</p> <p>Background</p> <p>The Estonian Postmenopausal Hormone Therapy (EPHT) Trial assigned 4170 potential participants prior to recruitment to blind or non-blind hormone therapy (HT), with placebo or non-treatment the respective alternatives. Before having to decide on participation, women were told whether they had been randomised to the blind or non-blind trial. Eligible women who were still willing to join the trial were recruited. After recruitment participants in the non-blind trial (N = 1001) received open-label HT or no treatment, participants in the blind trial (N = 777) remained blinded until the end of the trial. The aim of this paper is to analyse the effect of blinding on internal and external validity of trial outcomes.</p> <p>Methods</p> <p>Effect of blinding was calculated as the hazard ratio of selected chronic diseases, total mortality and all outcomes. For analysing the effect of blinding on external validity, the hazard ratios from women recruited to the placebo arm and to the non-treatment arm were compared with those not recruited; for analysing the effect of blinding on internal validity, the hazard ratios from the blind trial were compared with those from the non-blind trial.</p> <p>Results</p> <p>The women recruited to the placebo arm had less cerebrovascular disease events (HR 0.43; 95% CI: 0.26-0.71) and all outcomes combined (HR 0.76; 95% CI: 0.63-0.91) than those who were not recruited. Among women recruited or not recruited to the non-treatment arm, no differences were observed for any of the outcomes studied.</p> <p>Among women recruited to the trial, the risk for coronary heart disease events (HR 0.77; 95% CI: 0.64-0.93), cerebrovascular disease events (HR 0.66; 95%CI: 0.47-0.92), and all outcomes combined (HR 0.82; 95% CI: 0.72-0.94) was smaller among participants in the blind trial than in the non-blind trial. There was no difference between the blind and the non-blind trial for total cancer (HR 0.95; 95% CI: 0.64-1.42), bone fractures (0.93; 95% CI: 0.74-1.16), and total mortality (HR 1.03; 95% CI: 0.53-1.98).</p> <p>Conclusions</p> <p>The results from blind and non-blind trials may differ, even if the target population is the same. Blinding may influence both internal and external validity. The effect of blinding may vary for different outcome events.</p> <p>Trial registration</p> <p>[<a href="http://www.controlled-trials.com/ISRCTN35338757">ISRCTN35338757</a>]</p

Cervical cancer screening patterns among HIV-positive women in Estonia: a population-based retrospective cohort study.

The World Health Organisation (WHO) calls for the elimination of cervical cancer (CC) as a public health issue. To achieve elimination, efforts must be aligned and accelerated. Women living with HIV (WLWH) have excess risk for developing, and dying from, CC over the general population. Estimates of cervical cancer screening programme coverage in Eastern European countries that have experienced HIV epidemics since the early 2000's are scarce. This population-based retrospective study uses a healthcare administrative database and follows cohorts of all WLWH in a ratio of 1:3 randomly matched (age, region) HIV negative women from 2009 to 2018. Annual and longitudinal (over the whole study period) coverage for cervical cancer screening (opportunistic, organised, HIV specific) and adjusted odds ratios (AORs) for longitudinal screening coverage predictors were estimated from 2009 to 2018. Among WLWH and HIV-negative women, the mean annual coverage with opportunistic screening was 61.45 and 65.59%; and organised screening was 20.4 and 28.7%, respectively (both: p &lt; 0.00001). 19.01% (95% CI 18.05-19.97) HIV-negative and 13.9% (95% CI 12.35-15.45) WLWH were longitudinally covered with organised cervical cancer screening. Among WLWH, the mean annual HIV-specific cervical cancer screening coverage was 49.4, and 24.3% were longitudinally covered. Longitudinal coverage with HIV-specific cervical cancer screening was inversely associated with age, hepatitis C virus (HCV) co-infection (AOR 0.754, 95% CI 0.619, 0.916), not having insurance (AOR 0.331, 95% CI 0.264, 0.412), drug abuse (AOR 0.459, 95% CI 0.336, 0.618) and higher among those retained in HIV care (AOR 1.972, 95% CI 1.615, 2.410). Among HIV-negative women, longitudinal coverage with organised cervical cancer screening was inversely associated with residence in the region and higher among older women. Our results highlight unacceptably low coverage of cervical cancer screening of WLWH in Estonia. There is need for dedicated cervical cancer screening efforts for WLWH considering the high cancer risk and rate in the study population

Women's knowledge about cervical cancer risk factors, screening, and reasons for non-participation in cervical cancer screening programme in Estonia

<p>Abstract</p> <p>Background</p> <p>The attendance rate in Estonian cervical cancer screening programme is too low therefore the programme is hardly effective. A cross-sectional population based survey was performed to identify awareness of cervical cancer risk factors, reasons why women do not want to participate in cervical screening programme and wishes for better organisation of the programme.</p> <p>Method</p> <p>An anonymous questionnaire with a covering letter and a prepaid envelope was sent together with the screening invitation to 2942 randomly selected women. Results are based on the analysis of 1054 (36%) returned questionnaires.</p> <p>Results</p> <p>Main reasons for non-participation in the national screening programme were a recent visit to a gynaecologist (42.3%), fear to give a Pap-smear (14.3%), long appointment queues (12.9%) and unsuitable reception hours (11.8%). Fear to give a Pap-smear was higher among women aged 30 and 35 than 50 and 55 (RR 1.46; 95% CI: 0.82-2.59) and women with one or no deliveries (RR 1.56, 95% CI: 0.94-2.58). In general, awareness of cervical cancer risk factors is poor and it does not depend on socio-demographic factors. Awareness of screening was higher among Estonians than Russians (RR 1.64, 95% CI: 1.46-1.86). Most women prefer to receive information about screening from personally mailed invitation letters (74.8%).</p> <p>Conclusions</p> <p>Women need more information about cervical cancer risk factors and the screening programme. They prefer personally addressed information sharing. Minority groups should be addressed in their own language. A better collaboration with service providers and discouraging smears outside the programme are also required.</p

Cancer Rehabilitation Indicators for Europe

Little is known of cancer rehabilitation needs in Europe. EUROCHIP-3 organised a group of experts to propose a list of population-based indicators used for describing cancer rehabilitation across Europe. The aim of this study is to present and discuss these indicators. A EUROCHIP-3 expert panel reached agreement on two types of indicators. (a) Cancer prevalence indicators. These were proposed as a means of characterising the burden of cancer rehabilitation needs by time from diagnosis and patient health status. These indicators can be estimated from cancer registry data or by collecting data on follow-up and treatments for samples of cases archived in cancer registries. (b) Indicators of rehabilitation success. These include: return to work, quality of life, and satisfaction of specific rehabilitation needs. Studies can be performed to estimate these indicators in individual countries, but to obtain comparable data across European countries it will be necessary to administer a questionnaire to randomly selected samples of patients from population-based cancer registry databases. However, three factors complicate questionnaire studies: patients may not be aware that they have cancer; incomplete participation in surveys could lead to bias; and national confidentiality laws in some cases prohibit cancer registries from approaching patients. Although these studies are expensive and difficult to perform, but as the number of cancer survivors increases, it is important to document their needs in order to provide information on cancer control

The effects of postmenopausal hormone therapy on social activity, partner relationship, and sexual life – experience from the EPHT trial

<p>Abstract</p> <p>Background</p> <p>With the exception of sexual functioning and weight, social and behavioural effects of postmenopausal hormone therapy (HT) have not been reported from trials. This paper reports such results from the EPHT-trial in Estonia.</p> <p>Methods</p> <p>A randomized trial, with a blind and non-blind sub-trial in Estonia. From 1999–2001, 1778 women were recruited. The mean follow-up was 3.6 years. Women's experiences were asked in the first and final study year by mailed questionnaires (74 and 81% response rates). Comparisons of the groups were made by cross-tabulation and logistic regression, adjusting for age.</p> <p>Results</p> <p>There were no differences between the HT and non-HT groups in regard to being employed, the extent of social involvement or marital status or opinions on aging. There was no difference in the frequency of free-time exercise, or overweight. Some of the indicators suggested less sexual inactivity, but the differences were small.</p> <p>Conclusion</p> <p>In a trial setting, postmenopausal hormone therapy did not influence work or social involvement or health behaviour.</p> <p>Trial registration</p> <p>ISRCTN35338757</p

Evidence for reducing cancer-specific mortality due to screening for breast cancer in Europe: A systematic review

Background: The aim of this study was to quantify the impact of organised mammography screening on breast cancer mortality across European regions. Therefore, a systematic review was performed including different types of studies from all European regions and stringently used clearly defined quality appraisal to summarise the best evidence. Methods: Six databases were searched including Embase, Medline and Web of Science from inception to March 2018. To identify all eligible studies which assessed the effect of organised screening on breast cancer mortality, two reviewers independently applied predefined inclusion and exclusion criteria. Original studies in English with a minimum follow-up of five years that were randomised controlled trials (RCTs) or observational studies were included. The Cochrane risk of bias instrument and the Newcastle–Ottawa Scale were used to assess the risk of bias. Results: Of the 5015 references initially retrieved, 60 were included in the final analysis. Those comprised 36 cohort studies, 17 case–control studies and 7 RCTs. None were from Eastern Europe. The quality of the included studies varied: Nineteen of these studies were of very good or good quality. Of those, the reduction in breast cancer mortality in attenders versus non-attenders ranged between 33% and 43% (Northern Europe), 43%–45% (Southern Europe) and 12%–58% (Western Europe). The estimates ranged between 4% and 31% in invited versus non-invited. Conclusion: This systematic review provides evidence that organised screening reduces breast cancer mortality in all European regions wh

Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

<p>Abstract</p> <p>Background</p> <p>Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment.</p> <p>Methods</p> <p>The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization.</p> <p>Results</p> <p>After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT.</p> <p>Conclusion</p> <p>Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials.</p> <p>The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a financial risk, especially with licensed drugs. Public funding is crucial to avoid commercial biases. Legislation to share the costs of large post-marketing trials as well as regulation of manufacturer's participation is needed. [ISRCTN35338757]</p

Key indicators of organized cancer screening programs: Results from a Delphi study

Objective To maximize benefits and reduce potential harms of organized cancer screening programs in Europe, monitoring, quality assurance, and evaluation of long-term impact are required. We aimed to identify the most important indicators to be collected and reported. The study was designed to establish a consensus within a European-level working group and suggest a manageable list of key indicators. Methods We conducted a Delphi study among policymakers, researchers, and program coordinators who were experts in breast, cervical, or colorectal cancer screening. Study participants evaluated the importance of screening indicators on a 5-point Likert scale. Results The top 10 indicators by study participants were interval cancer rate, detection rate, screening attendance, screening coverage, cancer incidence