Investigating the potential non-authorized use of two different formulations of liraglutide in Europe: A real-world drug utilization study.

AIM: To assess the in-market use of Saxenda (liraglutide 3.0 mg) and Victoza (liraglutide 1.2 mg/1.8 mg) according to approved indications and posology. MATERIALS AND METHODS: This retrospective, non-interventional study was conducted at 41 sites from December 2016 to May 2019. Via medical record review, physicians at each site identified patients who had been prescribed Saxenda (Italy) or Victoza (Italy/Germany) within the 24 months following launch in each country. Pseudonymized data were abstracted on patient and site characteristics, indication for the prescription, posology and duration of usage. Adherence to the approved indications and posology, and to the Saxenda stopping rule, were assessed. No formal statistical analysis was performed. RESULTS: A total of 440 patients were prescreened and 225 (51.1%) were enrolled (Saxenda: N = 75, all in Italy; Victoza: N = 75 in Italy and N = 75 in Germany). In all, 96% (72/75) of Saxenda prescriptions, and 98.7% (148/150) of Victoza, were in accordance with the approved indications. Among the 40 patients treated with Saxenda for 16 weeks or longer, only two (5.0%) were confirmed as non-adherent to the stopping rule. Adherence could not be assessed in 23 (57.5%) patients because of missing body weight measurements. CONCLUSIONS: This retrospective, real-world post-authorization safety study provides reassurance that Saxenda and Victoza are primarily used according to the approved European label, thus their real-world utilization did not raise safety concerns.

Weight loss and risk reduction of obesity-related outcomes in 0.5 million people: evidence from a UK primary care database.

High body mass index (BMI) is known to be associated with various conditions, including type 2 diabetes (T2D), osteoarthritis, cardiovascular disease (CVD) and sleep apnoea; however, the impact of intentional weight loss on the risk of these and other outcomes is not well quantified. We examined the effect of weight loss on ten selected outcomes in a population from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Included individuals were >18 years old at the index date (first BMI value between January 2001 and December 2010). They were categorised by their weight pattern between year 1 post-index and year 4 post-index (baseline period) as having stable weight (-5% to +5%) or weight loss (-25% to -10%, plus evidence of intervention or dietary advice to confirm intention to lose weight). For inclusion, individuals also required a BMI of 25.0-50.0 kg/m2 at the start of the follow-up period, during which the occurrence of ten obesity-related outcomes was recorded. Cox proportional hazard models adjusted for BMI, comorbidities, age, sex and smoking status were used to estimate relative risks for weight loss compared with stable weight. Individuals in the weight-loss cohort had median 13% weight loss. Assuming a BMI of 40 kg/m2 before weight loss, this resulted in risk reductions for T2D (41%), sleep apnoea (40%), hypertension (22%), dyslipidaemia (19%) and asthma (18%). Furthermore, weight loss was associated with additional benefits, with lower risk of T2D, chronic kidney disease, hypertension and dyslipidaemia compared with maintaining the corresponding stable lower BMI throughout the study. This study provides objective, real-world quantification of the effects of weight loss on selected outcomes, with the greatest benefits observed for the established CVD risk factors T2D, hypertension and dyslipidaemia.

Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark.

INTRODUCTION: Service breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening. MATERIALS AND METHODS: Screening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50-69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional-historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register. RESULTS: For breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71-0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68-0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97-1.08). DISCUSSION: Benefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.

Breast cancer mortality in Norway after the introduction of mammography screening.

An organized mammography screening program was gradually implemented in Norway during the period 1996-2004. Norwegian authorities have initiated an evaluation of the program. Our study focused on breast cancer mortality. Using Poisson regression, we compared the change in breast cancer mortality from before to during screening in four counties starting the program early controlling for change in breast cancer mortality during the same time in counties starting the program late. A follow-up model included death in all breast cancers diagnosed during the follow-up period. An evaluation model included only breast cancers diagnosed in ages where screening was offered. The study group had been invited for screening one to three times and followed for on average of 5.9 years. In the follow-up model, 314 breast cancer deaths were observed in the study group, and 523, 404 and 638, respectively, in the four control groups. The ratio between the changes in breast cancer mortality between early and late starting counties was 0.93 (95% confidence interval [CI] 0.77-1.12). In the evaluation model, this ratio was 0.89 (95% CI: 0.71-1.12). In Norway, where 40% of women used regular mammography prior to the program, the implementation of the organized mammography screening program was associated with a statistically nonsignificant decrease in breast cancer mortality of around 11%.

Long-term Effectiveness and Safety of GH Replacement Therapy in Adults ≥60 Years: Data From NordiNet® IOS and ANSWER.

Context: Effectiveness and safety data on GH replacement therapy (GHRT) in older adults with adult GH deficiency (AGHD) are limited. Objective: To compare GHRT safety and clinical outcomes in older (≥60 years and, for some outcomes, ≥75 years) and middle-aged (35-<60 years) patients with AGHD. Design/setting: Ten-year follow-up, real-world data from 2 large noninterventional studies-NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web-Enabled Research (ANSWER) Program-were analyzed. Patients: GH-naïve and non-naïve patients with AGHD. Intervention: Norditropin® (somatropin). Main outcome measures: Outcomes included GH exposure, IGF-I standard deviation scores (SDS), body mass index (BMI), glycated hemoglobin (HbA1c), serious and nonserious adverse reactions (SARs and NSARs, respectively), and serious adverse events (SAEs). Adverse reactions were events with possible/probable causal relationship to GHRT. Results: The effectiveness analysis set comprised 545 middle-aged and 214 older patients (19 aged ≥75 years) from NordiNet® IOS. The full analysis set comprised 1696 middle-aged and 652 older patients (59 aged ≥75 years) from both studies. Mean GH doses were higher in middle-aged vs older patients. For both age groups and sexes, mean IGF-I SDS increased following GHRT, while BMI and HbA1c changes were similar and small.Incidence rate ratios (IRRs) did not differ statistically between older and middle-aged patients for NSARs [IRR (mean, 95% confidence interval) 1.05 (.60; 1.83)] or SARs [.40 (.12; 1.32)]. SAEs were more frequent in older than middle-aged patients [IRR 1.84 (1.29; 2.62)]. Conclusion: Clinical outcomes of GHRT in AGHD were similar in middle-aged and older patients, with no significantly increased risk of GHRT-related adverse reactions in older patients.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries.

INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (a basal insulin) and insulin aspart (a prandial insulin). The aim of this study was to investigate clinical outcomes in people with type 2 diabetes (T2D) after initiating IDegAsp treatment in a real-world setting. METHODS: This 26-week, open-label, non-interventional study was conducted in Australia, India, Malaysia, Philippines, Saudi Arabia, and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp from antidiabetic treatments (including oral antidiabetic drugs, basal insulin, basal-bolus insulin, premix insulin, and glucagon-like peptide 1 receptor agonist) per local clinical practice. RESULTS: Compared with baseline, there was significant improvement in HbA1c at end of study (EOS, first visit within weeks 26-36; estimated change - 1.4% [95% CI - 1.51; - 1.29]; P < 0.0001 [primary outcome]). From baseline to EOS, there were significant reductions in fasting plasma glucose (- 2.7 mmol/L [95% CI - 2.98; - 2.46]; P < 0.0001), body weight (- 1.0 kg [95% CI - 1.51; - 0.52]; P < 0.0001), and basal insulin dose in insulin-experienced participants (- 2.3 units [95% CI - 3.51; - 1.01]; P < 0.001). The incidence rates of non-severe (overall and nocturnal) and severe hypoglycaemia decreased significantly (P < 0.001) between the period before baseline and before EOS. CONCLUSION: In adults with T2D, initiating or switching to IDegAsp from previous antidiabetic treatment was associated with improved glycaemic control, lower basal insulin dose (in insulin-experienced participants), and lower rates of hypoglycaemia. TRIAL REGISTRATION: Clinical trial registration NCT04042441.

Mammography activity in Norway 1983 to 2008.

BACKGROUND: In Norway, an organized screening mammography program, the Norwegian Breast Cancer Screening Program (NBCSP) started in four counties in 1996 and became nationwide in 2004. We collected data on pre-program screening activity, and in view of this activity we evaluated the potential impact of the program on breast cancer mortality in Norway. METHODS: We searched data sources on mammography activity in Norway. Three data sources reported on examination activity, and two on self-reported examinations. We aimed at calculating annual number of women examined by mammography from 1983 to 2008, and coverage rate in program and non-program Norwegian counties. RESULTS: The annual number of women examined increased from 5000 in 1983 to 110,000 in 1993 to reach its maximum of 131,000 in 2002, excluding program examinations. The annual number of women examined in the organized program increased from 1996 to a steady state about 190,000 in 2004. Prior to start of the organized program, 40% of women in target age groups reported to have had mammography examination. During the years 1996-2002, 64% of first participants in the organized program reported to have been examined previously. Assuming that the Norwegian program would in absence of prior screening have decreased breast cancer mortality by 25%, and that the activity in- and outside the organized program were equally effective, the measured effect of the organized program would under actual circumstances be a reduction of 11%. CONCLUSION: The example of Norway illustrates that although monitoring of screening outcome is highly warranted, this may be seriously jeopardized if use of mammography examinations was widespread prior to implementation of an organized program.

Complication-specific direct medical costs by body mass index for 13 obesity-related complications: a retrospective database study.

BACKGROUND: Obesity, a multifactorial disease associated with many severe complications, affects more than 40% of adults in the United States. OBJECTIVE: To quantify the cost burden of 13 obesity-related complications (ORCs), overall and by body mass index (BMI) class. METHODS: Adult patients (aged ≥ 18 years) with ≥ 1 medical claim with an ICD-9/10 diagnosis code for the ORC of interest were identified using linked data from IQVIA's Ambulatory Electronic Medical Records and PharMetrics Plus. Thirteen ORCs were separately assessed (asthma, dyslipidemia, gastroesophageal reflux disease [GERD], heart failure with preserved ejection fraction [HFpEF], hypertension, musculoskeletal pain, obstructive sleep apnea [OSA], osteoarthritis [OA] of the knee, polycystic ovary syndrome [PCOS], prediabetes, psoriasis, type 2 diabetes mellitus [T2DM], and urinary incontinence); ORC cohorts were not mutually exclusive. For each ORC, the first claim identified for the ORC from January 2010-December 2016 was termed the index date. Patients had continuous enrollment in the 1-year pre-index (without a diagnosis code of the specific ORC under study) and the 1-year post-index, with ≥ 1 BMI value in the 6-months pre-index. Patients with underweight (BMI < 18.5 kg/m2) and those with cancer or pregnancy were excluded. Complication-specific costs were identified as claims with a diagnosis code for the ORC (primary position only for hospitalizations) or ORC-specific medications or procedures. Baseline demographic/clinical characteristics and complication-specific costs over the 1-year follow-up were assessed for each ORC cohort, overall and by BMI class (18.5-24.9; 25.0-29.9; 30.0-34.9; 35.0-39.9; ≥ 40 kg/m2). The association between total complication-specific costs and BMI class was assessed by generalized linear regression model for each ORC, adjusting for baseline characteristics. RESULTS: The total number of patients that comprised the ORC cohorts ranged from 1,275 (HFpEF) to 101,784 (musculoskeletal pain). Across ORC cohorts, 41.6% (musculoskeletal pain) to 73.5% (OSA) had obesity (BMI ≥ 30 kg/m2). For 4 ORC cohorts, more than one fifth of patients had class III obesity (BMI ≥ 40 kg/m2): T2DM, OSA, PCOS, and HFpEF. Baseline mean Charlson Comorbidity Index score increased with increasing BMI class for most ORC cohorts. The most costly ORCs overall based on mean total 1-year cost were: OA of the knee ($3,697 [range from normal weight (BMI: 18.5-24.9 kg/m2) to class III obesity: $2,453-$4,518]), HFpEF ($3,586 [range: $3,402-$4,685]), OSA ($2,768 [$2,442-$2,974]), and psoriasis ($2,711 [$2,131-$3,292]). The highest cost differences (≥20%) were observed among those with class III obesity versus those with normal weight for these aforementioned ORCs, as well as for GERD ($1,719 [$1,484-$1,893]) and asthma ($1,531 [$1,361-$1,780]). Following adjustment, most cost comparisons by BMI class were significantly higher versus those for normal weight for 6 ORCs. CONCLUSIONS: ORCs are important drivers of the economic burden of obesity, indicating an unmet need for the treatment of obesity. Appropriate weight management may reduce ORC-associated costs. DISCLOSURES: This study and its publication were supported by Novo Nordisk. Divino, Anupindi, and DeKoven are employed by IQVIA, which received funding from Novo Nordisk for this study. Ramasamy, Eriksen, Olsen, and Meincke are employed by and shareholders of Novo Nordisk. Material reported in this manuscript was presented in an abstract accepted by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2020, to be published in Value in Health. There was no presentation at ISPOR 2020.

Obesity, cardiovascular risk and healthcare resource utilization in the UK.

AIMS: Obesity and cardiovascular diseases (CVDs) often co-occur, likely increasing the intensity of healthcare resource utilization (HCRU). This retrospective, observational database study examined the joint effect of obesity and cardiovascular risk status on HCRU and compared HCRU between body mass index (BMI) categories and CVD-risk categories in the UK. METHODS: Patient demographics and data on CVD and BMI were obtained from the UK Clinical Practice Research Datalink. Cardiovascular risk status, calculated using the Framingham Risk Equation, was used to categorize people into high-risk and low-risk groups, while a CVD diagnosis was used to define the established CVD group. Patients were split into BMI categories using the standard World Health Organization classifications. For each CVD and BMI category, mean number and costs of general practitioner contacts, hospital admissions and prescriptions were estimated. RESULTS: The final study population included 1,600,709 patients. Data on CVD status were available on just over one-quarter of the sample (28.6%) and BMI data for just less than half (43.2%). The number of general practitioner contacts and prescriptions increased with increasing BMI category for each of the three CVD-risk groups. The group with established CVD had the greatest utilization of all components of healthcare resource, followed by high CVD risk then low CVD-risk groups. CONCLUSION: Increasing BMI category and CVD-risk status both affected several HCRU components. These findings highlight the importance of timely obesity management and treatment of CVD-risk factors as a means of preventing increasing HCRU.

Socio-demographic determinants of participation in mammography screening.

Our objective was to use individual data on socio-demographic characteristics to identify predictors of participation in mammography screening and control to what extent they can explain the regional difference. We used data from mammography screening programmes in Copenhagen, 1991-1999, and Funen, 1993-2001, Denmark. Target groups were identified from the Population Register, screening data came from the health authority, and socio-demographic data from Statistics Denmark. Included were women eligible for at least 3 screens. The crude RR of never use versus always use was 3.21 (95%CI, 3.07-3.35) for Copenhagen versus Funen, and the adjusted RR was 2.55 (95%CI, 2.43-2.67). The adjusted RR for never use among women without contact to a primary care physician was 2.50 (95% CI, 2.31-2.71) and 2.89 (95% CI, 2.66-3.14), and for women without dental care 2.94 (95% CI, 2.77-3.12) and 2.88 (95% CI, 2.68-3.10) for Copenhagen and Funen, respectively. Other important predictive factors for nonparticipation were not being married and not being Danish. In conclusion, to enhance participation in mammography screening programmes special attention needs to be given to women not using other primary health care services. All women in Copenhagen, irrespective of their socio-demographic characteristics, had low participation. Screening programmes have to find ways to handle this urbanity factor.

Performance of systematic and non-systematic ('opportunistic') screening mammography: a comparative study from Denmark.

OBJECTIVES: Evaluation and comparison of the performance of organized and opportunistic screening mammography. METHODS: Women attending screening mammography in Denmark in 2000. The study included 37,072 women attending organized screening. Among these, 320 women were diagnosed with breast cancer during follow-up. Opportunistic screening was attended by 2855 women with 26 women being diagnosed with breast cancer. Data on women attending screening were linked with information on cancer status. Each woman was followed with respect to diagnosis of breast cancer (invasive as well as in situ) for a period of two years. Screening outcome and cancer status during follow-up were combined to assess whether the result of the examination was true-positive, true-negative, false-positive or false-negative. Based on this classification, age-adjusted sensitivity and specificity of organized and opportunistic screening were calculated. RESULTS: Defining BI-RADS(trade mark) 4-5 as a positive screening outcome, the overall sensitivity of opportunistic screening was 33.6% and the specificity was 99.1%. Using BI-RADS(trade mark) 3-5 as positive, the sensitivity was 37.4% and the specificity was 97.9%. Organized screening (which was not categorized according to BI-RADS(trade mark)) had an overall sensitivity of 67.2% and a specificity of 98.4%. CONCLUSION: Our study showed a considerably higher sensitivity in organized screening than in opportunistic screening, while the specificity was fairly similar in the two settings. The findings support implementation of population-based breast screening programmes, as recommended in the 'European guidelines for quality assurance in breast cancer screening and diagnosis'.

Is there an association between liraglutide use and female breast cancer in a real-world setting?

BACKGROUND: Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza®) and more recently at 3.0 mg/day for weight management (Saxenda®). During the evaluation of liraglutide for approval in weight management, a minor imbalance in the numbers of reported breast neoplasms was observed, motivating the present study. Our objective was to quantify the association between liraglutide and incidence of breast cancer (BC) among women in a real-world setting. PATIENTS AND METHODS: Women initiating liraglutide or other antidiabetic therapies and who were enrolled in a large US health plan (2010-2014) were included. Comparisons of BC incidence rates were made between matched cohorts of initiators of liraglutide and cohorts of initiators of exenatide, metformin, pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors separately and as two "all comparators" groupings: with or without exenatide. Women with two or more claims with BC diagnosis codes within 61days of each other were identified as possible cases, with additional confirmation by clinician review of comprehensive claims listings. Propensity score matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed via Poisson regression. A latency analysis was performed. RESULTS: Relative risks for BC for liraglutide vs comparators from the ITT analyses ranged from 0.90 (95% CI: 0.67-1.22) for both the "all comparator" and "all comparator except exenatide" cohorts to 1.46 (95% CI: 0.96-2.22) relative to exenatide. Latency analyses excluding the first year of follow-up yielded slightly attenuated point estimates. The TOD analyses of cumulative use of liraglutide suggested no increased risk of BC. CONCLUSION: Neither the ITT (overall or latency analysis) nor cumulative TOD analyses suggested an elevated risk of BC among liraglutide initiators. Short length of follow-up and the potential for confounding by unmeasured factors limit the full assessment of long-term risk.

Predicting the risk of a false-positive test for women following a mammography screening programme.

OBJECTIVES: The objectives of this study was to provide a simple estimate of the cumulative risk of a false-positive test for women participating in mammography screening. To test the method, we used data from two well-established, organized mammography screening programmes offering biennial screening to women aged 50-69 years in Copenhagen and Fyn, Denmark. METHODS: We defined the outcome from a screen as being either a false-positive test or not a false-positive test. We then tested whether the outcomes from subsequent screens were independent, and afterwards estimated the risk over 10 screens of a false-positive test, i.e. the risk of getting at least one false-positive test for a woman participating in all 10 screens typically offered in Europe. RESULTS: The outcomes of subsequent screens were found to be independent. After completion of screening rounds 3-5, the risk of a false-positive test over 10 screens was predicted to be 15.8-21.5% for a woman participating in the programme in Copenhagen, and 8.1-9.6% for a woman participating in the programme in Fyn. CONCLUSIONS: Our study showed that a relatively robust prediction of the risk of a false-positive test over 10 screens can be calculated in a simple way relatively early after the start of a mammography screening programme.

[Mammographic screening in the county of Copenhagen. Clinical consequences of the first three screening rounds]. / Mammografiscreening i Københavns Kommune. Kliniske konsekvenser efter de første tre screeningsrunder.

INTRODUCTION: Service mammography has been offered biennially to women aged 50-69 years in the municipality of Copenhagen since 1991. The results were compared to breast cancer cases before initiation of screening. The comparison concerns prognostic factors and the treatment-related consequences. MATERIAL AND METHODS: Data from the Copenhagen service mammography screening were linked to data from the DBCG database. RESULTS: Before screening, 16% of breast cancer cases had a tumour size of 10 mm or less, this percentage increased to 41 in the screen-detected cases. Sixty per cent of breast cancer cases showed no evidence of metastatic spread to axillary lymph nodes before screening; this percentage increased to 78 per cent in the screen-detected cases. Forty per cent of ductal carcinomas showed a malignancy grade I before screening, compared to 53% in the screen-detected cases. Thirteen per cent were treated with breast conserving therapy before screening, as opposed to 48% in the screen-detected cases. Forty-one per cent needed postoperative adjuvant treatment before screening, compared with 21% in the screen-detected cases. DISCUSSION: A marked improvement was seen in the prognostic and treatment-related characteristics of the screen-detected breast cancer cases, as compared to breast cancer cases from the same area before screening was initiated.

[Mammography screening in the county of Copenhagen. Results of the first three screening rounds]. / Mammografiscreening i Københavns Kommune. Populationsresultater fra de første tre screeningsrunder.

INTRODUCTION: Biennial service mammography screening for breast cancer has been offered to women aged 50-69 years in the municipality of Copenhagen since 1991. We report the results of the first three invitation rounds. MATERIAL AND METHODS: Data were collected from the Copenhagen service mammography screening database and other Danish registers. RESULTS: The average participation rate during the first three invitation rounds was 66%. The breast cancer detection rate was 10/1,000 screened in the first invitation round and 5/1,000 in the consecutive rounds. The probability of a false positive mammography was 6% at the prevalent screen, and this was reduced to 3% at incidence screens. Fifty-two cases of interval cancer were seen after the first invitation round. The expected number was 152, which gives a proportional interval cancer rate of 0.34. The sensitivity was 86% and the specificity 94% after the first round. DISCUSSION: The detection rate of breast cancer was high, especially in the prevalence round. The trend in the incidence of breast cancer at the subsequent rounds was similar to that before screening, which indicates that mammography screening does not lead to any greater over-diagnosis. The rate of false positive mammography was high at the initial screening round, but was acceptable at subsequent rounds, and a false positive mammography does not seem to have affected participation in subsequent rounds. The Copenhagen screening programme conforms to international quality assurance guidelines for process evaluation.

Overdiagnosis in screening mammography in Denmark: population based cohort study.

OBJECTIVE: To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography. DESIGN: Population based cohort study. SETTING: Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark. PARTICIPANTS: 57,763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009. MAIN OUTCOME MEASURES: Overdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups. RESULTS: In total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening. CONCLUSIONS: On the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval -3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.

Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England.

OBJECTIVES: To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50-69 years. SETTING: The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50-69 years. METHODS: We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974-2004 and 1974-2003, respectively). We used Poisson regression for statistical inference. RESULTS: A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. CONCLUSIONS: The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.