Cost-effectiveness of case-based training for primary care physicians in evidence-based medicine of patients with coronary heart disease.

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EURO PEAN SO CIETY O F CARDIOLOGY ®

Original scientific paper

Cost-effectiveness of case-based training for primary care physicians in evidence-based medicine of patients with coronary heart disease

European Journal of Preventive Cardiology 0(00) 1–8 ! The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487315583798 ejpc.sagepub.com

Susanne Groot-Jensen1, Anna Kiessling1, Niklas Zethraeus2, Marie Bjo¨rnstedt-Bennermo1 and Peter Henriksson1

Abstract Background: We have shown that a case-based training programme for general practitioners, aimed to implement evidence-based care of patients at very high risk of coronary death, was associated with decreased mortality. In the present study we assessed long-term cost-effectiveness of this programme. Design: Registry-based long-term cost-effectiveness analysis on a clinical trial. Methods: Costs of the programme, health care, drugs and added years of life were included. Costs were adjusted to 2012 level and discounted by 3%. Life-years gained were estimated as the difference between the survival curves of the trial. The effectiveness measure, quality adjusted life-years (QALYs), was constructed by multiplying each life-year with a quality of life weight corresponding to the health status of that year. QALYs were also discounted by 3%. Incremental cost-effectiveness ratio (ICER) was estimated as the incremental cost per QALY gained. Results: The number of undiscounted life-years gained was 365 days in the intervention group as compared to control (p ¼ 0.02). The number of discounted QALYs gained was 0.66. The net increase in total costs was estimated as 17,862 E when costs of added years of life were included and 4621 E exclusive of these costs. This implied an ICER of 27,063 E per gained QALY. This ICER is well below commonly used threshold values of the societal willingness to pay for a QALY. Conclusions: The results show that a case-based training programme of general practitioners is a cost-effective way to save years of life in patients with very high risk of coronary death.

Keywords Coronary disease, secondary prevention, case-based training, cost analysis, quality-adjusted life years, time trade off method, quality of health care Received 19 January 2015; accepted 2 April 2015

Introduction Evidence-based routine practice is still far from achieving guideline goals in cardiovascular disease prevention of patients at high risk of death in coronary heart disease (CHD).1–4 This gap between evidence-based goals and achieved results in routine care of CHD patients has been shown in several countries.1 Such gaps also exist in many other major disease entities.5 Numerous studies have aimed to diminish this gap. However, only a few have demonstrated significant effects as regards patient outcomes and improvement of evidencebased clinical practice.6–8 Brusamento and colleagues8 evaluated single and multifaceted implementation strategies with active involvement of learners, with a focus on

implementation of evidence-based practice of common major diseases in primary care in Europe. Only four (19%) of 21 studies fulfilling the inclusion criteria reported interventions that were effective. We performed one of 1 Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Sweden 2 Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Sweden

Corresponding author: Anna Kiessling, Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, SE 182 88 Stockholm, Sweden. Email: [email protected]

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European Journal of Preventive Cardiology 0(00)

these.9,10 This study has also been assessed by others to be effective with a low risk of bias.7,11 The previous study was a randomised controlled pragmatic trial aimed at changing clinical practice of general practitioners in primary care towards greater adherence to evidence-based guidelines on cardiovascular disease prevention.9 We designed a case-based training programme and applied principles of adult learning to educate general practitioners in the intervention group, and assessed effectiveness as survival benefit for their CHD patients. After 10 years, the proportion of patients in the intervention group who had died was only half of that in the control group (p ¼ 0.02).10 This change in all-cause mortality was driven by a change in cardiovascular disease mortality (p ¼ 0.01).10 However, if case-based training is to be recommended on a broad basis in continuing medical education (CME), it is of utmost importance to show that the effects were achieved in a cost-effective way. Brusamento et al.,8 for example, asked for future research including economic evaluations of implementation programmes. Only a few such studies have assessed costs,12,13 and even fewer have performed a cost-effectiveness analysis.14 To the best of our knowledge no study has previously assessed the long-term cost-effectiveness of a programme, which used active learning methods such as case-based training. The aim of the present study was to assess cost-effectiveness of this case-based training programme for general practitioners in primary care in evidence-based secondary prevention of patients at very high risk of coronary death.

Methods Study design The hypothesis behind this study is that case-based training for primary care physicians in evidence-based medicine of patients with coronary heart disease is costeffective. The cost-effectiveness analysis was based on a randomised controlled intervention trial, assessing the effect of case-based training of evidence-based secondary prevention of very high-risk coronary patients. The intervention was performed during two years (1995– 1997). The analysis was conducted from a societal perspective and included costs both within and outside the health care system during the study period 1995–2006. Both costs and quality adjusted life years (QALYs) were discounted using a 3% discount rate.15 All costs were first expressed in the prices of 2012 in Swedish crowns (SEK). If necessary, costs were inflated to the prices of 2012 using the Consumer Price Index (CPI) of Statistics Sweden.16 Finally, costs were converted to E using the average exchange rate of 2012 (1 E ¼ 8.7 SEK).

Table 1. Baseline characteristics of physicians and primary health care centres. Characteristic

Intervention

No. of physicians 26 Mean (SD) age (years) 47.0 (6.3) No.(%) women 9 (35) No. of primary health care centres with: 4999 inhabitants 2 5000–9999 inhabitants 2 10,000 inhabitants 3 Location Urban population 5 Mixed urban and rural population 2

Control 28 46.4 (4.8) 9 (32) 2 3 2 5 2

SD: standard deviation.

Setting and participants in the pragmatic clinical intervention trial The study region comprised 95,000 inhabitants. Primary care was delivered by 54 general practitioners at 14 primary healthcare centres (PHCs). These centres were divided into two balanced groups as previously described (Table 1).10 Approximately 1700 patients had CHD in the study region.17 A sub-group of them were identified by a register at the local hospital of the region. In this register we found 323 patients less than 70 years with a valid diagnosis of CHD who were invited to participate in the study. Sixty-eight patients declined to participate, leaving 255 patients to be included in the study. By asking the patients, we identified their responsible general practitioner and PHC. On the basis of this information, we divided the patients according to the two previously mentioned PHC groups. Patients in the two groups had similar characteristics, as presented in Table 2. This resulted in two balanced groups of PHC and patients. These two groups were randomly allocated to intervention or control, leaving 45 patients in the intervention group and 43 patients in the control group. The remaining 167 patients had their follow-up at a specialist/ cardiologist and therefore not included in our analysis. All participating patients gave written informed consent and approved a two-year clinical trial at the time of inclusion. The Regional Ethical Review Board in Stockholm, Sweden also approved this trial (Dnr 2007/ 805-32) concerning collection of register data. The Ethical Review Board did not deem the de-identified retrieved registry data to be an intrusion of personal integrity.

The case-based training programme All general practitioners were invited to a lecture on the new local practice guidelines and received them in



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Table 2. Baseline characteristics of included patients. Baseline characteristics

Total

Intervention

Control

Patients included Age (years) Females Current smoker Systolic BP (mm Hg) Diastolic BP (mm Hg) Tot. cholesterol (mmol/l) Triglycerides (mmol/l) HDL cholesterol (mmol/l) LDL cholesterol (mmol/l) TTO EQ-5D

88 62.4 (6.8) 13 (15%) 19 (22%) 141 (19) 84 (9) 6.3 (1.0) 2.1 (1.1) 1.2 (0.3) 4.2 (0.9)

45 62.6 (6.1) 8 (18%) 10 (22%) 142 (19) 84 (10) 6.3 (1.0) 2.1 (1.2) 1.2 (0.4) 4.2 (0.8) 0.82 (0.26) 0.8 (0.17)

43 62.3 (7.4) 5 (12%) 9 (21%) 139 (20) 85 (8) 6.2 (1.1) 2.1 (1.0) 1.1 (0.3) 4.1 (1.0) 0.86 (0.23) 0.79 (0.25)

p-value

0.93 0.55 0.89 0.59 0.70 0.59 0.88 0.78 0.62

BP: blood pressure; EQ-5D: EuroQol; HDL: high density lipoprotein cholesterol (mmol/l); LDL: low density lipoprotein cholesterol (mmol/l); SD: standard deviation; TTO: time trade off. Patient characteristics are presented by group of responsible physician at baseline. Intervention denotes patients treated by general practitioners (GPs) in the intervention group. Control denotes patients treated by GPs in the control group. Data are mean (SD) or number of patients (%). Values of p refer to a comparison between the intervention and the control group.

printed form. In addition, physicians in the intervention group participated in a programme consisting of recurrent interactive case-based training seminars at their own primary health care centre during 1995–1997.9

Costs of inpatient care, the case-based training programme and drugs Costs were estimated as the unit cost multiplied by the quantities of resources used. Data for the costeffectiveness assessment were retrieved and calculated for the whole study period from inclusion during 1995 to the end of the study period in 2006. Costs of inpatient care were calculated by multiplying the number of hospital admissions classified by diagnosisrelated groups (DRGs) with the corresponding cost per hospital admission. We used the Swedish personal identity number (PIN) a 10-digit unique identifier to retrieve data on all inpatient care from the prospective National Patient Register (NPR) from the inclusion date to 31 December 2006. NPR is a valid register that contains information on date of admission and discharge, main and secondary diagnoses and procedures. Diagnoses were recorded according to the International Classification of Diagnoses (ICD), ninth version (ICD-9) prior to 1996 and the tenth version from 1997 (ICD-10). The Statistical Classification of Diseases and Related Health Problems is a widely accepted standard, published by the World Health Organization (WHO) and is translated by the National Board of Health and Welfare in Sweden. Admissions according to ICD-9 had to be revised to ICD-10. We also retrieved data of mortality from the Causes of Death register. Information on main

diagnoses, procedures and number of days per admission was retrieved. Each admission was grouped into a unique DRG-weighting that enabled calculation of the cost of inpatient care during follow-up. This was conducted by using software from Datawell AB (Gothenburg, Sweden). Inpatient costs were possible to calculate in 99% of all admissions. The DRG-weighting was multiplied by the Swedish national cost per DRG-weighting of 2006 (DRG-weighting 1¼36,576) SEK corresponding to 4204 E and inflated to the cost of 2012 by use of the national CPI.16 This provided actual costs for all in-hospital admissions of each patient during follow-up. All cost assessments were performed without knowledge of group affiliation (intervention or control). The case-based training programme consisted of three to four seminars that lasted one hour and were held during a two-year period at the respective PHCs of the intervention group. The cost of the case-based training programme was calculated by multiplying the number of hours spent by different professionals (general practitioners and facilitator) in the programme, including time of preparation, travelling and seminars, by their hourly gross wage rate (including pay roll taxes). We used mean salaries, in Stockholm County Council, of general practitioners respectively facilitator (mean salary of hospital-based consultants) in the analysis. Costs of the case-based programme per patient were calculated based on prevalence of CHD at involved PHCs (n ¼ 1667) in the study region.17 The costs of lipid-lowering drugs were calculated based on defined daily doses (DDDs) and the number of days that a patient was on medication multiplied by the price as extracted from the price list of Swedish Medical Products.18



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Costs of added years of life An intervention that increases survival results in changes of production and changes in both medical and non-medical consumption that should be taken into account in a cost-effectiveness analysis from a societal perspective. To reflect a societal perspective net difference between total consumption (medical and non-medical) and production of the added years of life was included in the cost-effectiveness analysis.19 We calculated costs of the added years of life based on the figures presented by Ekman.20

Health effects Health effects were measured in terms of QALYs. QALYs take into account both changes in quantity and quality of life and are constructed by adjusting life years for the quality of life in which they are spent. To calculate QALYs the number of years in different health states were multiplied by a quality weighting between zero (for death) and one (for full health), which reflect the relative desirability of the different states. The quality of life weighting can be estimated using direct methods such as rating scale (RS), time trade-off (TTO) or standard gamble (SG).21 Another alternative is to use prescored value systems that generate quality of life TTO weights for EuroQol (EQ-5D) health states.22,23 In this study we used the TTO method to estimate quality of life weightings in the base case analysis. Each individual was asked to state, within a future time frame of ten years, the number of years in full health followed by death that was deemed as being equivalent to a specific number of years in his/her present health state followed by death. To obtain the quality of life weight the number of years in full health was divided by ten years in the present health state. This yielded a TTO quality weighting between zero and one. EQ-5D was used to estimate quality of life weightings in the uncertainty analysis. Quality of life assessed at baseline was used in the QALY calculations, because it was necessary to use a time point for QALY assessment when all patients were still alive. The quality of life assessments seemed to be very stable. During the first two years there were no significant change.13

Definition of cost-effectiveness To assess the cost-effectiveness of the case-based training programme, first the incremental cost-effectiveness ratio (ICER) was estimated. The ICER is defined as the incremental cost per QALY gained. For the case-based training programme to be cost-effective the cost per QALY gained must be below a threshold value corresponding to how much society is willing to spend in order to gain a QALY. We defined the case-based

training programme to be cost-effective if the cost per gained QALY was below 80,000 E.24 Approximately the same threshold value can also be derived from the value that the Swedish road authorities put on a statistical life.

Uncertainty analyses Both sensitivity and statistical analyses were used to assess uncertainty. In the sensitivity analysis we calculated ICERs also by using the pre-scored value systems to generate quality of life TTO weightings for the calculation of QALYs22,23 and at different discount rates for health effects and costs. To assess EQ-5D each patient classified their own health status into five health dimensions: mobility, self-care, usual activities (e.g. work, studies, housework, family or leisure activities), pain/discomfort, within three levels of severity: no problems, moderate problems, severe problems. The resulting individual combination of the five scores defined a health state (out of 243 possible health states). Each health state was then converted to a quality of life weighting by using the pre-scored UK and Swedish value sets.22,23 To further represent statistical uncertainty in the costeffectiveness analysis due to sampling variability a costeffectiveness acceptability curve (CEAC) was constructed based on a parametric approach25. This curve can be interpreted in terms of the probability that the casebased training programme is cost-effective for different threshold values of willingness to pay for a QALY25,26 and shows the probability at the chosen cut-off value (of 80,000 E) for the case-based training programme to be cost-effective (Alt stryka for the case-based training programme). An alternative interpretation is that CEAC is the mirror image of a p value curve for the test of whether the case-based training programme is cost-effective. Continuous variables were expressed as mean and standard deviation (SD), and categorical variables were expressed as frequencies, percentages, or both, unless otherwise stated.

Results As shown in Table 2 there were no significant differences in baseline characteristics between patients in the intervention and control groups. Quality of life according to TTO was 0.82 in the intervention group and 0.86 in the control group at baseline.

Costs of inpatient care, case-based training programme, drugs and gained life-years The patients in the intervention group had a mean of 3.3 in-patient care episodes during follow-up.



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Table 3. Costs and health effects of the case-based training programme by group during the study period (12.3 years). COSTS

Intervention

Control

In-patient care Case-based training programme Drugs Sum costs Costs of life-years gained Sum total costs HEALTH EFFECTS Life-years (undiscounted) Life-years gained (undiscounted) Life-years (discounted) Life-years gained (discounted) QALYs (discounted) QALYs gained (discounted) ICER (3%) Including costs of life-years gained Excluding costs of life-years gained

16,356 5 63 16,424 13,241 29,664

11,782

11,803

10.8

9.8

9.3

8.5

21 11,803

Difference intervention control 4574 5 42 4621 13,241 17,862

1 0.78 7.8

7.2 0.66 27,063 7001

ICER: incremental cost-effectiveness ratio; QALYs: quality adjusted life years. Costs are quoted in E (1E ¼ 8.7 Swedish crowns (SEK)). All costs are expressed as mean costs/patient by group. Discount rate 3%. ICER is net costs divided by net effects.

Mean DRG weighting was 3.9 per patient in the intervention group and 2.8 per patient in the control group. The mean number of days as in-patients was 18.2 days in the intervention group and 15.3 days in the control group. All costs of in-patient care, case-based training programme, drugs and gained life-years are shown in Table 3. The mean cost of health care amounted to 16,356 E per patient in the intervention group and 11,782 E per patient in the control group. As shown in Figure 1 the increased costs in the intervention group were mainly due to coronary heart disease. A third of the patients had no in-patient care during the study. The cost of the case-based training programme was 5 E per patient. Cost of lipid lowering drugs increased by 42 E in the intervention group as compared to controls. Total cost of the case-based training programme, drugs and in-patient care was 16,424 E per patient in the intervention group and 11,803 E per patient in the control group. Thus the net increase in cost was 4621 E. Cost of gained life-years was 13,241 E per patient. This implies that the net increase in total costs were 17,862 E.

Health effects The number of (undiscounted) life-years gained was one year (365 days) in the intervention group as compared to control (Table 3). This increase in life expectancy is equal to the difference between the survival curves in the pragmatic clinical trial. Discounting by

18000 16000 14000 12000 Other diseases

10000 8000

Other Cardiovascular Diseases

6000

Coronary Heart Disease

4000 2000 0 Control

Intervention

Figure 1. Distributions of in-patient care costs of coronary heart disease, other cardiovascular diseases respectively noncardiovascular diseases in intervention and control groups during follow-up. Costs are discounted by 3% and costs per patient adjusted to 2012-year level and shown in E (1E¼8.7 Swedish crowns (SEK)).

3% resulted in 0.78 gained life-years (285 added life days). The number of (discounted) QALYs gained was 0.66.

Cost-effectiveness The incremental cost-effectiveness ratio i.e. net gain in discounted total costs divided by net gain in discounted QALYs was 27,063 E per QALY as compared to



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Table 4. Sensitivity analyses with different quality adjusted life years (QALYs) and different discount rates for costs and health effects. QALY Costs discounted by 3% TTO TTO EQ-5D1 EQ-5D1 EQ-5D2 EQ-5D2 Costs discounted by 5% TTO TTO EQ-5D1 EQ-5D1 EQ-5D2 EQ-5D2

Discounted by

ICER

3% 0% 3% 0% 3% 0%

27,064 21,264 28,810 22,328 25,517 19,847

5% 0% 5% 0% 5% 0%

28,107 18,738 29,698 21,245 26,233 17,489

EQ-5D: EuroQol; ICER: incremental cost-effectiveness ratio; TTO: time trade off. ICER is net costs divided by net effects. EQ-5D1 is calculated by using the English tariff. EQ-5D2 is calculated by using the Swedish tariff. Costs are quoted in E (1E ¼ 8.7 Swedish crowns (SEK)).

control. This value is well below the societal threshold value of 80,000 E.24

Results of the uncertainty analyses As shown in Table 4 the resulting ICERs varied between 17,489 and 29,698 E when using different discount factors and different methods to calculate QALYs. The cost-effectiveness acceptability curve in Figure 2 shows that the probability increases with the societal willingness to pay for a gained QALY. At our defined threshold value of 80,000 E, the probability is 0.82 that the case-based training programme is cost-effective.

Discussion This study indicate that it is cost-effective to train general practitioners how to practise evidence-based secondary prevention of CHD. Patients gained one year of life, which was modified to quality-adjusted years. Commonly used thresholds for cost-effectiveness are usually found in the range between 40,000–80,000 E, although values above 80,000 E have also been suggested.24 Our estimated cost-effectiveness ratio of 27,063 E is well below this range of values and indicates that the case-based training programme is cost-effective. Our previously reported long-term pragmatic trial demonstrated that case-based training was associated

with a decreased mortality driven by a decrease in coronary deaths.10 The programme was aimed to improve general practitioners care of patients at very high risk of coronary death in accord with evidence-based guidelines. The intervention was performed at the participating general practitioners own health care centres and cases were set in the general practitioners own context i.e. a pragmatic trial in all respects.27 The cost-effectiveness analysis was based on a societal perspective, which means that costs resulting from an increase in the length of life should be included.19 To reflect a societal perspective the net difference between total (medical and non-medical) consumption and production during life years gained was included in the cost-effectiveness analysis. However, because most other studies have not included costs of added years of life, for comparability we also present the cost-effectiveness results without these costs. Furthermore, quality adjustment is needed to calculate QALYs, which provide the currently recommended outcome measure in cost-effectiveness analysis.21 We used the TTO technique to assess quality of life and calculate QALYs, which is the method usually recommended in health economic evaluations. However, to test the robustness of our ICER calculation we performed a sensitivity analysis using the UK and Swedish pre-scored value systems for EQ-5D22 for estimation of QALY-weightings. Furthermore, we varied discount rates from 0–5%. The sensitivity analyses resulted in ICERs ranging between 17,000–30,000 E. Such ICERs are all below generally accepted estimates of the societal willingness to pay for a QALY. We have also included a cost-effectiveness acceptability curve to illustrate the probability that the case-based training programme was cost-effective for different willingness to pay (WTP) prices for QALYs. This curve showed a high probability that the intervention is cost-effective. Thus the performed uncertainty analyses confirm that the cost-effectiveness of the intervention is a robust finding. Discounting is the process of determining the present value of future benefits and costs. Discounting may have a substantial effect on the ICERs, in particular when benefits and costs are expected to occur in the distant future. In our base case analysis both costs and QALYs were discounted and at the same discount rate. However, in the sensitivity analyses only costs were discounted as well. As reported earlier this did not change the conclusions. It is well known that there is a gap between evidencebased goals and achieved results in routine clinical practice even concerning other cardiovascular diseases such as heart failure, atrial fibrillation and stroke, as well as in other related disease areas such as diabetes and renal dysfunction. We could assume that we used




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1.00 0.90 0.80

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0.70 0.60 0.50 0.40 0.30 0.20 0.10

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Figure 2. A cost-effectiveness acceptability curve (CEAC) showing the probability that the case-based training programme is costeffective for different willingness to pay (WTP) prices.

case-based active training in CME of evidence-based practice for general practitioners concerning all these disease areas. This would mean a need of 18–24 h during two years, or just one hour per month and general practitioner to improve the quality of care of all these major cardiovascular disease areas. From a Swedish perspective with the least number of in-hospital beds per inhabitant in Europe and also the lowest number of in-hospital days per admission, it is up to the outpatient caregiver to deliver quality-assured care. Today, we see that this is not the case, as patients do not reach their set treatment goals. Limited financial resources thus really put a focus on cost-effectiveness and quality assured methods. A strength of our cost-effectiveness study is that it was based on a pragmatic clinical trial performed in the real-world context of participating general practitioners and high-risk patients. Furthermore, it was a long-term study during 12.3 years. Note that the increase in life expectancy only refers to the difference between survival curves in the pragmatic clinical trial. Potential survival gains after the end of the follow-up in the clinical trial are not accounted for in the analysis. The outcome mortality is a robust health effect measure. Further strengths are that the costs analysed are the real costs of health care and intervention as reflected in clinical practice. Uncertainties in the cost-effectiveness analysis concerning choice of method to estimate quality of life weightings and discount rates were tested

in a sensitivity analysis, which showed that the costeffectiveness results were robust. A limitation of the study is the number of included patients. However, at the time, it was not possible to identify all patients in the study area. The included patients were all consecutive patients in the hospital register during the study period and we had no indications that the included patients differed from the rest of the population. Further limitations are that not all costs were included in the analysis. For example productivity costs due to changes in working status and costs for outpatient care were not included in the analysis.

Conclusion To conclude, the results of the economic analysis of this pragmatic trial show that case-based training for general practitioners in secondary prevention for patients at very high risk of coronary death was cost-effective. Funding The authors gratefully acknowledge grants provided by the Stockholm County Council (ALF project), Sweden and funds of the Karolinska Institutet.

Conflict of interest None of the authors have any conflict of interests.



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Acknowledgements Abstract with results from this study were elected ‘‘Best poster’’ for one of the highest scored posters presented at the Annual Congress of European Society of Cardiology 2013, Amsterdam, the Netherlands.

References 1. Gyberg V, Kotseva K, Dallongeville J, et al. Does pharmacologic treatment in patients with established coronary artery disease and diabetes fulfil guideline recommended targets? A report from the EUROASPIRE III cross-sectional study. Eur J Prev Cardiol. Epub ahead of print 1 April 2014. PMID: 24691153. 2. Hickling J, Rogers S and Nazareth I. Barriers to detecting and treating hypercholesterolaemia in patients with ischaemic heart disease: Primary care perceptions. Br J Gen Pract 2005; 55: 534–538. 3. Majumdar SR, McAlister FA and Furberg CD. From knowledge to practice in chronic cardiovascular disease: A long and winding road. J Am Coll Cardiol 2004; 43: 1738–1742. 4. Hobbs FD and Erhardt L. Acceptance of guideline recommendations and perceived implementation of coronary heart disease prevention among primary care physicians in five European countries: The Reassessing European Attitudes about Cardiovascular Treatment (REACT) survey. Fam Pract 2002; 19: 596–604. 5. Rabe KF, Adachi M, Lai CK, et al. Worldwide severity and control of asthma in children and adults: The global asthma insights and reality surveys. J Allergy Clinical Immunol 2004; 114: 40–47. 6. Marinopoulos SS, Dorman T, Ratanawongsa N, et al. Effectiveness of continuing medical education. Evid Rep Technol Assess (Full Rep) 2007; 1–69. 7. Forsetlund L, Bjorndal A, Rashidian A, et al. Continuing education meetings and workshops: Effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2009: CD003030. 8. Brusamento S, Legido-Quigley H, Panteli D, et al. Assessing the effectiveness of strategies to implement clinical guidelines for the management of chronic diseases at primary care level in EU Member States: A systematic review. Health Policy 2012; 107: 168–183. 9. Kiessling A and Henriksson P. Efficacy of case method learning in general practice for secondary prevention in patients with coronary artery disease: Randomised controlled study. Br Med J 2002; 325: 877–880. 10. Kiessling A, Lewitt M and Henriksson P. Case-based training of evidence-based clinical practice in primary care and decreased mortality in patients with coronary heart disease. Ann Fam Med 2011; 9: 211–218. 11. Unverzagt S, Oemler M, Braun K, et al. Strategies for guideline implementation in primary care focusing on patients with cardiovascular disease: A systematic review. Fam Pract 2014; 31: 247–266.

12. Frijling BD, Lobo CM, Hulscher ME, et al. Intensive support to improve clinical decision making in cardiovascular care: A randomised controlled trial in general practice. Qual Saf Health Care 2003; 12: 181–187. 13. Kiessling A, Zethraeus N and Henriksson P. Cost of lipid lowering in patients with coronary artery disease by case method learning. Int J Technol Assess Health Care 2005; 21: 180–186. 14. O’Reilly D, Holbrook A, Blackhouse G, et al. Cost-effectiveness of a shared computerized decision support system for diabetes linked to electronic medical records. J Am Med Inform Assoc 2012; 19: 341–345. 15. Gold MR, Siegel JE, Russel LB, et al. (eds) Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996. 16. Statistics Sweden. Consumer Price Index (CPI). http:// www.scb.se/en_/Finding-statistics/Statistics-by-subjectarea/Prices-and-Consumption/Consumer-Price-Index/ Consumer-Price-Index-CPI/Aktuell-Pong/33779/ Consumer-Price-Index-CPI/272151/ (2015, 14 November 2012). 17. The Public Health Agency of Sweden. Public health report Stockholm County Council 1999. [Folkha¨lsorapport, Only available in Swedish.] 18. La¨kemedelsindustrifo¨reningens Service AB (Lif). FASS 2012: La¨kemedel i Sverige (Swedish Medical Products). Stockholm, Sweden. 19. Meltzer D. Accounting for future costs in medical costeffectiveness analysis. J Health Econ 1997; 16: 33–64. 20. Ekman M. Studies in health economics: Modelling and data analysis of costs and survival. The Economic Research Institute. Stockholm: Stockholm School of Economics, 2002. 21. Drummond MF, Sculpher MJ, Torrance GW, et al. Methods for the economic evaluation of health care programmes. 3rd edn. New York: Oxford University Press, 2005. 22. Burstrom K, Sun S, Gerdtham UG, et al. Swedish experience-based value sets for EQ-5D health states. Qual Life Res 2014; 23: 431–442. 23. Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35: 1095–1108. 24. Hirth RA, Chernew ME, Miller E, Fendrick AM and Weissert WG. Willingness to pay for a quality-adjusted life year: In search of a standard. Med Decis Making 2000; 20: 332–342. 25. Lothgren M and Zethraeus N. Definition, interpretation and calculation of cost-effectiveness acceptability curves. Health Econ 2000; 9: 623–630. 26. Briggs AH and Gray AM. Handling uncertainty in economic evaluations of healthcare interventions. Br Med J 1999; 319: 635–638. 27. Davis D. Can CME save lives? The results of a Swedish, evidence-based continuing education intervention. Ann Fam Med 2011; 9: 198–200.


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Lipid control in patients with coronary heart disease treated in primary care or cardiology clinics.

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Primary care training for patent medicine vendors in rural Nigeria.

Physicians focus on primary care for patients with HIV.

Training community-based primary care physicians in the screening and management of mental health disorders among Latino primary care patients.

A new approach to training primary care physicians: a four-year combined internal medicine-family practice residency for seniors.

Counseling role of primary care physicians in preventing early childhood caries in children with congenital heart disease.

Patients' Perceived Quality of Family Physicians' Primary Care with or without 'Family Medicine' in the Clinic Name.

Primary medical care and training programs in general internal medicine.

[The PROPRESE trial: results of a new health care organizational model in primary care for patients with chronic coronary heart disease based on a multifactorial intervention].

A training program for primary care physicians improves the effectiveness of ultrasound surveillance of hepatocellular carcinoma.

Involvement of Primary Care Physicians in the Decision Making and Care of Patients With Breast Cancer.

Primary care physicians are under-testing for celiac disease in patients with iron deficiency anemia: Results of a national survey.

Primary care physicians' knowledge of sleep medicine and barriers to transfer of patients with sleep disorders. A cross-sectional study.

Primary care physicians' refusal to care for patients infected with the human immunodeficiency virus.

[Non-alcoholic fatty liver disease. Role of primary care physicians].

Risk of coronary heart disease in patients with HIV infection.

Incorporating three-dimensional printing into a simulation-based congenital heart disease and critical care training curriculum for resident physicians.

Cancer patients' concerns: congruence between patients and primary care physicians.