Aim: Several studies have tried to quantify overdiagnosis of prostate cancer with Prostate-specific antigen(PSA) screening, but estimates vary widely. This study aims to evaluate the degree of overdiagnosis of prostate cancer with 10 or 14 follow-up years after the stop of screening in Finland. Methods: We selected 80379 men aged 55-69 years who were randomized to a screening or a control arm, distinguishing four birth cohorts: 1941-44,1937-40, 1933-36 and 1929-32. The first PSA screening test occurred during1996-1999. Men without detected as prostate cancer in the previous screening would be invited to the next screening 4 years later. The estimate of overdiagnosis is the ratio of the cumulative excess incidence to the cumulative incidence of prostate cancer in the screened group after the year-specific incidence became stable. Results: The patterns of all incidences in these four cohorts have not become stable yet, and the difference of cumulative incidence in the current longest follow- up years is the best estimate of overdiagnosis so far. Conclusion: Overdiagnosis rates of prostate cancer in people who received screening in Finland was estimated as 2.27%,15.4%, 11.4%, and 10.2% for 1929-32, 1933-36,1937-40, and 1941-44 cohorts, respectively. / Thesis / Master of Science (MSc)

The aim of this thesis was to assess test use from primary care. Test use is an essential part of general practice, yet there is surprisingly little data exploring and quantifying its activity. My overarching hypothesis was that test use from primary care is sub-optimal, specifically that tests are overused (overtesting) - ordered when they will lead to no patient benefit, and underused (undertesting) - not ordered when they would lead to patient benefit. Previous metrics used to identify potential over and undertesting have been categorised into direct and indirect measures. Indirect measures take a population-level approach and are 'unexpected variation' in healthcare resource use, such as geographical variation. Direct measures consider individual patient data and directly compare resource use with an appropriateness criterion (such as a guideline). In this thesis, I examined three indirect measures: temporal change in test use, between-practice variation in test use and variation between general practices in the proportion of test results that return an abnormal result. In chapter 3, I identified which tests have been subject to the greatest change in their use from 2000/1 to 2015/16 in UK primary care. In chapter 4, I identified the tests that had been subject to the greatest between-practice variation in their use in UK primary care. In chapter 5, I present a method to identify General Practices whose doctors order a lower proportion of tests that return a normal result. In chapter 6, I present a method to directly quantify over and undertesting; I conducted a systematic review of studies that measured the adherence of general practitioner's test use with guidelines. In chapter 7 I acknowledge that the use of guidelines to audit general practitioner's test use is flawed; guidelines are of varying quality and not designed to dictate clinical practice. In this chapter, I determine the quality and reporting of guidelines, the quality of the evidence underpinning their recommendations and explore the association between guideline quality and non-adherence. Overall, I have shown that most tests have increased substantially in use (MRI knee, vitamin D and MRI brain the most), there is marked between-practice variation in the use of many tests (drug monitoring, urine albumin and pelvic CT the most) and that some general practices order a significantly lower proportion of tests that return an abnormal result. I have also shown that there is marked variation in how often GPs follow guidelines, but guidelines based on highly quality evidence are adhered to significantly more frequently. Lastly, in my Discussion chapter, I discuss the implications of my thesis, how it fits into the wider literature and an idea for a proposed step-wise approach to systematically identify overtesting.

Background The debate regarding the lower age limit for mammography service screening is old and lively; a product in part of the lower breast cancer risk in younger ages as well as the limited data available for studies of the younger age group. Recently the idea of inviting only high risk groups has gained momentum, however high risk might not be equivalent to greater benefit from screening. Therefore, there is a need for information on effectiveness of screening as it relates to young women and to specific risk groups. To this end, this thesis evaluates mammography screening for the age group – 40 to 49 year old women – in terms of breast cancer mortality reduction in total and in subgroups based on breast cancer risk factors. Overdiagnosis of mammography screening is also evaluated for women 40 to 49 years old. In addition, this thesis presents a statistical method to estimate this effectiveness and to test for differences in effectiveness between subgroups adjusted for non-compliance and contamination. Methods The studies of this thesis are based on data from the Screening of Young Women (SCRY) database. The SCRY database consists of detailed information on diagnosis, death, screening exposure and risk factors for breast cancer cases and population size by year (between 1986 and 2005) and municipality for women in Sweden between 40 and 49 years old. The material was divided into a study group consisting of the counties that invited women in the age group 40-49 years to mammography screening, and a contemporaneous control group consisting of the counties that did not. Effectiveness was estimated in terms of rate ratios for two different exposures (invitation to and participation in screening), and overdiagnosis for subsequent screening was estimated adjusting for lead time bias. Defining a reference period enabled adjustment for possible underlying differences in breast cancer mortality and incidence. A statistical model for adjusting for non-compliance and contamination in randomised controlled trials was further developed to allow for adjustment in cohort studies using a Poisson model with log-linear structure for exposure and background risk. Results During the study period (1986-2005), there were 619 and 1205 breast cancer deaths and 6047 and 7790 breast cancer cases in the study group and the control groups, respectively. For women between 40 and 49 years old, the breast cancer mortality reduction was estimated at 26% [95% CI, 17 to 34%] for invited to screening and 29% [95% CI, 20 to 38%] for attending screening. The RR estimates for the high-risk groups based on the risk factors parity, age at birth of first child, and socio-economic status were equal to or higher than that of the low risk groups. The new statistical method showed that the decrease in effectiveness with parity was not a statistically significant trend. The overdiagnosis from subsequent screening for 40 to 49 year old women was estimated at 1% [95 % CI, -6 to 8 %] (i.e., not statistically significant). Conclusion Subgroup specific effectiveness was also estimated. The relative effectiveness of screening for breast cancer with mammography for women age 40 to 49 years appears to be comparable to that for older women. These findings and the fact that there was no statistically significant overdiagnosis from subsequent screening speak for inviting women 40 to 49 years old to screening. High-risk screening for nulliparous women aged 40 to 49 years, for example, might be an alternative in countries where population-based screening for all women between 40 and 49 years old is not possible. However, the matter of risk factors and the effect of their combinations is complex and risk group screening presents ethical and practical difficulties. The new statistical model is a useful tool for analysing cohorts with exposed and non-exposed populations where non-compliance and contamination is a potential source of bias.

In 2014, breast cancer was the second leading cause of death among Canadian women, with women over age 50 years making up 82% of the identified cases. To address this issue, the Ontario Breast Screening Program developed a media campaign that promoted the benefits of mammogram screening, but not the associated risks (i.e., false-positive, false-negative, radiation exposure, and overdiagnosis). This study was designed to determine whether there was a statistically significant relationship between knowledge of overdiagnosis and participation in mammogram screening. This cross-sectional, correlational study used schema theory supported by the effective health communication model. Forty-one women were invited to listen to a brief presentation on the benefits and risks of screening mammograms and then completed a modified Champion Health Belief Model Scale survey. Two sample t tests and logistic regression analyses of the survey scores showed that the data did not support any correlations with education and screening, but did indicate a correlation between overdiagnosis and participation. The less a participant felt that overdiagnosis was a negative consequence, the more likely they were to participate in breast screening. Survey participants also stated that promotions of mammograms should present balanced information about the benefits and risks of screening. The positive social change and policy implications of this study include providing women aged 50-69 years more information on overdiagnosis in mammograms so they are more informed participants in the decision-making process, and educating Ontario government policymakers with information about the barriers that women aged 50-69 years face in getting balanced information on mammography programs.