Irresponsible and responsible resource management in obstetrics

Accepted Manuscript Irresponsible and Responsible Resource Management in Obstetrics Birgit Arabin, MD, PhD

PII:

S1521-6934(17)30011-1

DOI:

10.1016/j.bpobgyn.2016.12.009

Reference:

YBEOG 1690

To appear in:

Best Practice & Research Clinical Obstetrics & Gynaecology

Received Date: 9 November 2016 Revised Date:

16 December 2016

Accepted Date: 19 December 2016

Please cite this article as: Arabin B, Irresponsible and Responsible Resource Management in Obstetrics, Best Practice & Research Clinical Obstetrics & Gynaecology (2017), doi: 10.1016/ j.bpobgyn.2016.12.009. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Irresponsible and Responsible Resource Management in Obstetrics For: BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY

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Ethical Issues in Human Reproduction Issue 31.6

Birgit Arabin, MD, PhD

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Center for Mother and Child, University Clinics Marburg – Giessen, Philipps-University Marburg Baldinger Str. 1, 35034 Marburg- Germany

Telephone (work): +49 6421 5869043 Computer-Fax:

+49 721 509663784

Portable:

+49 15150470484

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Clara-Angela Foundation Center for Research and Development Witten, Alfred Herrhausen Str. 44 58455 Witten-Germany Villa Clara Angela Koenigsallee 36 14037 Berlin- Germany,

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Corresponding author: Birgit Arabin Sybelstr. 6 35037 Marburg – Germany

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Mail: [email protected]

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Word Count: 6999 (without legends, references, abstract) Word count abstract: 112

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ABSTRACT Low budgets constrain and high budgets stimulate choices. In high-income countries, this economic

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reality may lead to overuse in health care and to unnecessary risks for mothers and infants. Options for improvement can be created at different levels of health care systems. Pregnancy provides an effective opportunity to profile maternal risks and represents a vulnerable, but potentially modifiable period

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from prenatal life to adulthood. In response to system-inherent false incentives professional responsibility requires obstetricians to strive to improve future health of families and their offspring,

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despite disincentives for doing so. This chapter addresses professionally responsible resource management in obstetrics and identifies implications for patients, care givers, communities, policy makers and academic faculties.

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KEY WORDS: Shared decision making, maternal-fetal medicine, risks and benefits, choosing wisely

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criteria, ethical resource allocation, research and training in obstetrics and gynecology.

“Perfection of means and confusion of goals seem to characterize our age. Even if only a small part of

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mankind sincerely and passionately strives for safety, welfare and the free development of talents their superiority will prove itself in the long run.” (Albert Einstein)

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INTRODUCTION Substantive justice requires that medical needs and resources are reasonably and fairly balanced [1].

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Low-resourced countries suffer from limited access to health care or to minimal technology [2]. Their under-fulfilled needs should increase our concerns that in high-resourced countries patients are exposed to overuse or misuse of care [3]. Ethical concepts with a global perspective are helpful, but

implemented with political accountability [5].

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not enough [4]. Worldwide, family care must be supplemented with affordable interventions that are

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In Maternal-Fetal Medicine (MFM), we care for at least two patients. This clinical ethical complexity creates challenges about whether procedures can be adequately justified on the basis of medical efficacy, safety and costs. Fetal and neonatal patients cannot ask for nor refuse treatments. Neither children nor mothers control economic resources [1]. Associations among pregnancy, diseases,

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interventions, and long-term outcome of mother and children are multifactorial. In order to understand and responsibly manage these associations and the interplay among physicians, health care institutions, research, education and other stakeholders, transparency is essential.

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Physicians should not put their own economic interests above their patients’ interest [6]. After being offered a grant for a medical business program in the United States (US) the author of this article

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rejected a relationship with a prestigious campus because its primary focus on business and administrative interests. Professional responsibility and economic interests can also clash during daily clinical life. Some obstetricians might have better management skills than the new generation of business managers and controllers. However, the primary motivation of obstetricians as healthcare professionals is to reduce suffering and as researchers to advance scientific discovery and its clinical application.

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This article contains subjectively selected issues and leaves open questions. It is not meant to stimulate the innocent reader to float like a dead fish within a stream which is increasingly polluted by self-

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defense and commerce but rather to reach an inflection point and swim like a salmon before reproduction towards the academic fountains of our specialty. Multicultural experience helps upstream swimmers against backflow and turbulence, to balance strengths and constraints, and to put

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costs into the proper professional perspective.

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A BRIEF REVIEW OF ECONOMIC ANALYSIS IN THE CLINICAL SETTING Although the nomenclature of economic analysis can seem remote from clinical practice, to ignore it

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would be a mistake. Deriving from Latin “surgere” (to rise) resource symbolizes an inner strength. Sometimes, we are left to our own resources. After productivity studies in the Hawthorne Company Mayo concluded that employees are far more motivated by relational factors than by monetary

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rewards or work environment [7]. Developments in organizational behavior claimed legitimacy for Human Resource Management (HR). Institutes of Personnel & Development and the societies for HR

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were founded. The expression HR can be abused, as by Stalin, who acknowledged its importance but applied brutality, secrecy and ambiguity [8]. In health care institutions, HR minimizes costs by acquiring appropriate staff and providing training and maintenance of competency. Engaged, fulfilled rather than abused health care workers and physicians, help optimize patient experience.

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Cost-effectiveness analyses (CEA) were used by farmers to measure productivity [9] and its use has become popular for many other applications. The CEA guide of the World Health Organization (WHO) stresses that CEA is only one input for the use of resources; interventions should also address

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inequalities [10]. The ethical principle of justice supports the concept of equity, which is the absence of avoidable or remediable differences. Life losses are calculated as years of potential life lost (YPLL),

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estimating years a person would have lived without premature death. Cost-benefit analysis (CBA) assesses the economic value of beneficial outcomes against the cost of achieving them. CEA and CBA have obvious clinical applications. It is therefore of interest that the number of obstetric publications with the Mesh-terms CBA versus CEA is less than 10%. The burden of disease measures mortality and disability-adjusted life years (DALYs) [11]. Although societies are severely affected by maternal mortality, there the correlation with DALYs is problematic

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[12]. Economic assumptions by cost/DALY as used in low-income countries cannot be generalized because human resources (e.g. availability of obstetricians) play a role. For example, costs/DALY by

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providing Cesareans for obstructed labor ranged from $251 in Madagascar to $3,462 in Oman [13]. With respect to unjustified maternal or neonatal death the use of CEA sounds harsh, because such outcomes are professionally unacceptable.

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The concept of quality-adjusted life year (QALY), whereby one QALY equates to one year in perfect health, has been more often used in high-income countries although its use for selective adjustment

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has been criticized [14]. The health-related benefits accrued over a woman's lifetime are reported as cost/QALY gained or incremental cost effectiveness ratio (ICER). Thresholds for investments have to be defined. ICER analysis can lead to controversial results for different age groups (e.g. screening for trisomy 21) [15] or when comparing different policies (e.g. fetal DNA blood group screening for

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targeted antenatal anti-D prophylaxis versus no or general prophylaxis) [16]. Meta-analyses and patient information leaflets use relative risk reductions (RRR), but should also show absolute risk reductions, because RRRs can wrongly suggest that benefits are large although the

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absolute risk is very small and the improvement is also very small but still a large percent of the original absolute risk [17]. The number needed to treat (NNT) or to prevent (NNP) characterizes the number of

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patients who need to receive clinical management in order to achieve target outcomes [18]. A threshold is the maximum number of patients a clinician is willing to treat to prevent one target outcome, the NNTt or the NNPt. [19]. The minimum event rate for treatment (MERT) justifies a treatment, calculated as MERT=1/(NNPt x RRR) [19]. The minimum control event rate (CERmin) is defined as CERmin=TER+(DC/(QALYs gained x $50000)), where TER represents a treatment event rate. Graphs of QALYs versus the logs of NNPt or CERmin illustrate under- or overuse of resources [20].

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In reality, the thresholds to prevent a disease will vary based on co-morbidities and the expected intervention efficacy (RRR): Patients with a history of pre-eclampsia (PE), a body mass index (BMI) > 30

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or assisted reproductive technology (ART) have a NNPt below 250 for low-dose aspirin to prevent PE expecting RRRs of 10-50% (Figure 1)[21]. Similar graphs for other conditions would allow obstetricians to integrate risk factors in a patient’s history into more rational decision making. QUALYs and ICERs

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should include long-term health of mother and child to favor early interventions [22].

The return on investment (ROI) is used by hospital managers who know the terms from portfolios: A

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high ROI means that gains compare favorably to cost [23]. Defining a “YEAR 0” eliminates the problem to estimate measures based on uncertain assumptions (Table 1). ROI/potential gained life years can be defined, which tripled by introducing family planning to prevent stillbirth and maternal mortality in South Africa [24]. Many calculations are only based on models and should be interpreted with caution.

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For details, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) provides checklists and supports for decision making.

Improvement research integrates continuous data collection with the work itself. Professionals should

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define core principles and create scientific improvement methods [25; 26]. Tips how to incorporate

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improvement research into daily work are published [27]. Should it not be part of every obstetric unit?

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PATIENT LEVEL Truth telling was endorsed as a professional obligation as early as 1903 [28]. Well-informed patients

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experience better quality of life [28]. Shared decision making can reduce participation in useless clinical cascades [29; 30]. The US Institute of Medicine and the US Center for Medicaid and Medicare Services named patient-centered care a fundamental aim of to improve health care [31; 32].

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Interrupting vicious circles before pregnancy

Preventing unhealthy life styles is a clinical challenge. Food industries spend billions to contribute to a

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global obesity epidemic and thereby nudge children to unhealthy eating habits that can last a lifetime. The prevalence of impaired glucose tolerance, hypertension, and raised cholesterol in European children were 8.4%, 21.8%, and 22.1%, respectively [33; 34]. An obese child will incur elevated medical costs of about USD $19,000 compared to a child with normal weight; additional maternity costs for

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severely obese women were about UKS £350.75 [35]. By 2020, the projected economic burden of obesity unrelated to pregnancy was estimated to rise by £1.9–2.0 billion/year in the United Kingdom (UK) or $48–66 billion/year in the US [36]. Risks track from childhood into adulthood as pregnancy

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complications, cardiovascular disease (CVD), hypertensive disorders (HD), or metabolic syndrome [37]. Fetuses of obese mothers already show signs of cardiac lesions within the 1st trimester [38].

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“Obesogens” program prenatal vascular insults [39], early postnatal death in animals [40] and humans [41] and cause vicious circles of non-communicable diseases (NCD) across generations. Protection could be achieved by restricting marketing of energy-dense, nutrient-poor foods and beverages [42] or targeting children and parents for healthy eating habits. Children were asked to help to develop joyful health programs [43]. Early diet-physical activity interventions are cost-effective [44] and prevented childhood obesity within randomized controlled trials (RCT) [45]. Media and apps are

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sources for adolescents, however produced to be sold and rarely neutral. This may be changed if clinical scientists would leave their “ivory towers” and engage the public, e.g., by utilizing social media.

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The ethical imperative for clinicians is to share information and for patients to be equal participants [46]. The partnership should already frame pre-conceptional lifestyles although there are benefits when obese pregnant women are instructed [47].

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Preventing unintended pregnancies diminishes maternal mortality rates (MMR) in low-income countries. In Nigeria, this public health measure reduced up to 1/5 of abortion-related deaths with

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ICERs of about USD $500/YLS, below the per capita gross domestic product (GDP) [48]. Among OECD countries, the US and Hungary had the highest adolescent pregnancy rates [49]. Early sexual activity in the Netherlands equaled that of the US, but unintended pregnancy rates were 7% versus 50%. Pragmatic contraceptive support in the Netherlands differs from the mixed message sent in the US to

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adolescents in an ambivalent society that suggests that premarital sex is romantic but immoral. For these pregnancies and infants, the US spends $11 billion in annual public insurance costs [50]. The UK ranks fourth worst in Europe [51]. Every £1 spent on contraception saves the public £11. A 10% cut for

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contraception could cost an extra £8.65 billion due to unwanted pregnancies or sexually transmitted infections (STI) [52]. More worrying is the likelihood of emotional, medical and educational harm that

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represents vicious circles of social inequity reducing life chances for mothers and children who again have low educational achievements and early pregnancy rates. Contraceptive-promoting interventions lowered teenage pregnancies with a RR of 0.66 and a 95% confidence interval (CI) of 0.50-0.87 [53]. Emphasizing condom use reduced “no prevention” with an odds ratio (OR) of 0.61 (0.45-0.85) [54]. A review concluded that subsequent births were reduced by home-based interventions, but that more rigorous programs need to be started as soon as possible after the first unintended delivery [55].

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Psychosocial interventions in the UK lowered teenage pregnancy rates [56]. A systematic review identified >200 apps, but their effectiveness was not evaluated [57]. Women overestimate risks of

to long-acting contraception [49]. Interrupting vicious circles during pregnancy

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long-acting reversible contraception [58], but imperfect adherence of teens should lead to easy access

Pregnant women have to make heuristic decisions. Neuroscientists distinguished between the small world

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where probabilities are so clear that patients can optimize decisions and the large world of uncertainty, where

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information is incomplete. Surprises are pre-programmed when physicians do not inform about equipoise. Functional magnetic resonance imaging showed that cerebral processes differ under both circumstances of decision-making [59]. Libertarian paternalists argue that authorities need to steer health decisions [60]. Gynecologists may not instruct “irrational” pregnant women although the same women would decide rationally when appropriately informed. Companies steer media reports: “Due to cell-free (cf)DNA, no sick babies will be

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born” was a headline in a German newspaper. However, obstetricians should inform women who wish a comprehensive assessment to choose for karyotyping and microarray analysis by invasive testing since loss rates are smaller (<0.1%) than speculated [61]. The first population-based non-industry funded trial randomized 2111

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French women with a risk for trisomy 21 of 1/250 to compare cfDNA and invasive testing. There was no difference in fetal loss rate (1.3% vs. 1.24%), but 13 additional abnormalities were diagnosed in the invasive

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group [62]. The NNT for cfDNA to detect (not treat) one case with trisomy 21 was 1266. Such studies should have been performed before the commercial introduction of cfDNA testing. Regrettably, regulations do not require comparisons of new and traditional practices and physicians are not critical enough. Vicious circles of

women’s avoidable ignorance could be minimized when parents were referred to neutral information before stress or emergency situations limit rational decision making. This holds true for other screening

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or treatment policies, such as threatened preterm birth, PE, or gestational diabetes (GDM). Fact boxes as proposed for cancer screening would be one option to inform patients neutrally (Table 2) [17].

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Interrupting vicious circles after pregnancy Diseases during pregnancy can have lifelong health implications predisposing low birth weight (LBW) and later health risks (Barker hypothesis) [63]. Pregnancy complications can indicate maternal or even

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grandparent’s risks for NCDs (reverse Barker hypothesis) [64]. Recently, we have reviewed the longterm impact of risk profiles for both mother and children to show the complex interplay of genetics

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and epigenetics [22]. Irritations provoked by unprofessional risk information have to be replaced by education and mutual care decision making, which can increase preventive healthcare [65]. Breastfeeding support is recommended for 6 months followed by 1 year with complementary foods [66]. Still, global sales of breast-milk substitutes reached $40 billion in 2013. Marketing targeted

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directly to “consumers” is widespread even in countries that have adopted the WHO policy to restrict such activities. Breastfeeding reduces risks and increases benefits: In the US, short breastfeeding rates result in 4981 yearly excess cases of breast cancer, 53,847 cases of hypertension, 13,946 cases of

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myocardial infarction and incur $17.4 billion resulting from premature death, $733.7 million in direct and $126.1 million in indirect morbidity costs [66]. In children, breastfeeding reduces infections,

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sudden infant death, leukemia, and asthma [68] and ameliorates cardiovascular remodeling induced by fetal growth restriction (FGR) [69]. In mothers, breastfeeding mobilizes fat, reduces rates of heart disease (HD), overactive stress responses, breast or ovarian cancer and protects women with GDM from type-2 diabetes [70]. Consultation and surveillance after pregnancy similarly decreases costs and risks: The American diabetes prevention trial supports a balanced diet and an active lifestyle after GDM [71]. In the UK, a

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mean ICER of £7355 was evaluated for weight management programs in obese mothers [72]. A 10% increase of treated early HD after PE would prevent 14,000 deaths [73]. A new Dutch guideline

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proposes to optimize modifiable risk factors of PE for cardiovascular disease (CVD) [75]. The US Centers for Disease Control recommends inter-pregnancy care [76]. Pregnancy data should be available lifelong: In Canada, women with a history of PE showed a 4-fold risk of death during cardiac interventions

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[77]. The American Heart Association includes GDM and high diastolic pressure in their assessment [78]. Text reminders to search controls are a creative concept [79]. A prospective US cohort trial is

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ongoing to establish more details [80]. Also children from mothers with PE are three times more likely to develop targetable hypertension as young adults [81].

The UN General Secretary Ban Ki-moon declared during the first NCD-conference of WHO and UNO: "We strive for an international commitment that puts NCDs high on the development agenda” [82].

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Down to earth, this declaration should be translated into family programs to interrupt vicious circles indicated by pregnancy–related syndromes. Obstetricians should change communication from questionable persuasion to something straightforward [60] and not neglect future health aspects of

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their patients [83]. Could co-production or person-centered care be new watchwords?

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PHYSICIAN LEVEL The wide variety of tests, procedures and medications that obstetricians use supports the hypothesis that obstetric care is insufficiently based on scientific standards but on clinicians’ readiness to follow

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fiduciary professionalism or (false) incentives. This is reflected by a disparity of priorities within one institution, country, or different systems. To rely on trusted professionalism disconnected from evidence-based reasoning seems naïve. Highlighting differences among physicians can threaten

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insecure specialists. Vices such as bias, primacy of self-interest, hard-heartedness, and corruption undermine a professional culture between patients and physicians [84; 85] or chairs and faculty

benefits for patients or society [83].

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colleagues [86]. In most settings, physicians are reimbursed for providing care units, regardless of

Deficits in obstetric care in high-income countries are more due to a lack of knowledge than to a lack of money [87]. The overflow of scientific publications has led to less trustworthy summaries in non-peer-

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reviewed journals or internet pages. Playing and listening to music or reading critics is not the same. A Statistical Literacy Questionnaire for Obstetrics and Gynecology (OBGYN) was distributed to US

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gynecologists, who did poorly on questions about facts, statistics or relationships with 0%, 7%, 36%, answering correctly; 49% could determine a positive predictive value [88]. If basic knowledge is lacking,

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scientific studies can hardly be interpreted, criticized or implemented. Low professional skills combined with fears of professional litigation result in rising costs, insurance premiums and then coverage restrictions. Employed obstetricians fulfill hospital-owed obligations if patients are not entitled to choose a physician or care is complex [89]. Worries about lawsuits have caused an increase in Cesarean delivery rates [90]. After adverse events, obstetricians cumulatively increase Cesareans by 8% and then have fewer malpractice incidents [91]. But the Cesarean epidemic

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has its price: The WHO estimated that worldwide 6.2 million Cesareans are unnecessary, but 3.2 million were needed, resulting in yearly costs of global “excess versus needed” Cesareans of $ 2.32

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billion versus $ 432 million [92]. Even worse are fetal and maternal risks in subsequent pregnancies [93]. Regional high rates of Cesareans cause increased risks of maternal mortality [92].

There is a deep gap between evidence and its clinical application, expressed as a steady drop from

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awareness, acceptance, applicability (diagnosis/treatment), availability and ability (competence), recall or agreement (patient’s opinion or interpretation) and adherence. In 50% of hospitals it took at least

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17 years until accepted medical innovations were introduced [94].

Utilizing Medline, the term “CEA” was related with core procedures and outcomes. This article can only provide an overview of the increasing publications and trials (Table 3). Ethical antidotes to control waste are to keep economic self-interest in its secondary place, to create cultures that reward humility

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in accepting correction and integrity, compassion, self-effacement and self-sacrifice [84]. Ethical skills reduce malpractice litigation [95] and discourage the arrogance of idiosyncratic judgments [84]. Professional societies and hospital directors may lose their professional compass, promoting so-called

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heroes of spectacular procedures like uterus transplantations, oocyte freezing or fetal surgery not based on evidence. Organizational leaders sometimes incentivize such physicians with honors,

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gambling with public attention and high ROIs and rarely allow questioning the burden for individuals, families and societies. A conflict of interest regarding blind ambition is not questioned, but has caused an “ethical Chernobyl” where even Nobel judges did not heed warnings of medical misconduct [96]. Team-workshops on routine procedures may be less spectacular, but help to improve everybody’s care and to save children from stillbirth or chronic disease [97]. Did some of us forget that our discipline is called Maternal-Fetal Medicine and not Maternal-Fetal Surgery?

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INSTITUTIONAL LEVEL Hospital leaders bear responsibility to support fiduciary professionalism [84]. No commercial airline

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would survive if it preferred to compensate for disasters instead of investing in safety and prevention. The improvement pioneer W.E. Deming stated: “When organizations focus on quality, quality tends to increase and costs fall over time; when they focus on costs, costs rise and quality declines”. He

Japanese industry and are still applied in perinatal care [98].

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advocated a “Plan-Do-Check-Act” cycle [26]. His management analysis and advices derived from

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In Germany, the trend that commercial companies run hospitals increased from 14.8% (1991) to 35.2% (2014) [99], although a meta-analysis involving 26,000 hospitals had shown that private for-profit compared to not-for-profit ownership results in a higher risks of death. Included was a study which showed increased perinatal death rates in private for-profit hospitals (RR 1.095, 95% CI 1.050-1.141;

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p<0.0001) [100]. Managers hop between settings, striving for maximized short-term revenue derived from diagnosis related groups (DRGs), although patient centered care is more sustainable [101]. If medical mentors do not report on patient outcomes, but on profits, the question remains why DRGs

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were defined if not for insurance payers to be re-invested in disease prevention? Business with diseases may not be more profitable than their prevention [102].

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For medical mistakes and unintended consequences, the management system is responsible for 85%, workforces only for 15% [26]. The Institute for Healthcare Improvement started to deal with perinatal care after a review of birth trauma events [98]. Perinatal quality control is also performed in Europe. Most importantly, obstetricians should improve the systems in which they work and not blindly adapt to each management proposal [98].

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Nosocomial infections and outbreaks with multi-drug-resistant organisms are a threat, mainly for preterm neonates. Low rates of antibiotic use combined with high rates of monotherapy are beneficial

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to reduce adverse events and resistance rates. Stewardship programs optimize antimicrobial therapy and improve patient safety [23]. Strategies for improvement of hand hygiene are cost-effective [103]. A global approach tested the implementation of the WHO’s strategy. The compliance was higher in

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low- and middle- (OR 4.67, 95%CI 3.16–6.89; p<0.0001) than in high-income countries (OR 2.19, 95%CI 2.03–2.37; p<0.0001) [104]. Welfare and hierarchical structures seem not to be fertile ground for

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evidence-based instructions, although proactive infection control is vital. Increasing efforts for training, cultures, and adherence to dress codes earned back investments and prevented suffering [23] (Table 1). For interventions to prevent HIV mother-to-child transmission a quadruple ROI was observed in New York apart from the more essential reduction of suffering [105].

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Obstetric team working impacts outcomes [106]. Expensive birth simulators cannot pretend a high teaching status, because the equipment is prone to defects and lacks evaluation of appropriate training methods. Last but not least, a RCT showed that confidence levels were higher when low-cost models

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were used whereby performance did not differ [107]. A systematic review found 97 articles on obstetric team training, skills and communication [108]. Meanwhile, a RCT with CEA examining the

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perinatal outcome after centered team training is ongoing [109]. External and internal audits of maternal and perinatal mortality and severe morbidity reflect institutional integrity. Classifying substandard factors (SSF) can induce institutional improvement and insight into problem areas by inter-rater agreement measures [110]. After the introduction of Dutch perinatal audits in 2010, at least one SSF was identified in 53% of 1102 term perinatal deaths. Within

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two years, perinatal mortality decreased from 2.3 to 2.0/1000 births (p<0.00001); antepartum selection of high risk cases improved (p=0.0001) [111].

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Safety programs also analyze perinatal and maternal mortality and deficits in communication (72%), organizational culture (55%) and competency (47%) [112]. They encourage a proactive approach and focus on interpersonal dynamics in risky situations, where skills and commitment truly matter. Safety

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features include “high reliability organizing” aspects with roots in industries where failure has drastic consequences (aviation, nuclear power). The US Joint Commission proposed quality measures such as

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elective Cesarean delivery without indication or neonatal infections with bacteremia. Using a “Plan-DoStudy-Act” design 20 centers in Ohio reduced inappropriate scheduled births from 25% to 5% [113]. Crew-resource management is more important than financial resource management. Within a cluster RCT decision-to-incision time was decreased for Cesarean deliveries in the intervention group [114].

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Curricula for residents and staff members with defined competences are essential. As many complex oncologic patients are not followed by obstetricians, administrators should care that obstetric high risk patients are treated by the most competent MFM-members and nurse-practitioners. The Society for

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Maternal-Fetal Medicine (SMFM) in the US has defined co-management for obstetricians [115]. Sadly, this is insufficiently realized and represents inequity for the most vulnerable voiceless patients.

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Obstetric guidelines and computerized standards should be institutionalized to teach and identify SSF. The countrywide quality and implementation of guidelines differs considerably. A “Choosing Wisely” campaign aimed to establish negative guidelines about practices that lack evidence of benefit in “Top-Five Lists” [116]. This has been realized by the SMFM and the American Academy of Pediatrics. We have started a choosing wisely project with residents in Germany. Talking about unnecessary procedures is a first step to responsibly allocate institutional resources.

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Overarching organizations may support institutions to achieve gold standards in health care to guarantee organizational quality. The digital industry has shifted to focus on user experience. Similarly,

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medical innovation has to re-shift to emphasis how people come together in the pursuit of patient safety and satisfaction. Can human resource management focus on independent minds and

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intellectual, ethical and communicative skills?

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COMMUNITY LEVEL Traditions, cultures, life styles, social inequalities, demography and health care systems determine how

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the GDP is distributed [117]. Commercial health care systems imply a paradox: If a commercial product is better and cheaper it is successful. To provide better health care and reduce costs results in reduced expenditures for the community but also in reduced revenues for physicians or hospitals. Patients are

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not inclined to pay for better and cheaper care unless reimbursement is refused. They tend to demand transparency only when exposed to out-of-pocket costs. Therefore, shareholder companies publish

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their balances in some countries. Although we share costs for health care, however, outcome data of health care providers, industry, institution, insurances, community bureaucracy, and conflicts between involved groups are not published. Physician salaries only make up 20%, but their recommendations up to 60% of overall spending [118].

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OECD data demonstrate that total expenditures do not correlate with fertility rates, quality of care, or equity. In 2013, health spending as a share of GDP ranged from 5.1% in Turkey, 8.5% in the UK, 11% in Germany and Sweden to 16.4% in the US [117]. The US spends $8233/person compared with an

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average of $3268/person in OECD countries.

A fertility rate of 2.1 children/ woman ensures a stable population. In 2014, fertility rates were 1.4 in

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Germany, 1.95 in France and the US, and 3.3 in India; teenage fertility rates were 5.8 in Sweden and France, 9.8 in Germany, 28.4 in the UK and 49.8 in the US. Rates of low birth weight (LBW) ranged from 4.2 in Sweden, 6.8 in Germany, 7.4 in the UK to 9.4 in the US although the number of antenatal visits did not differ; infant mortality was 2.8 in Sweden, 3.8 in Germany, 5 in the UK and 6.9 in the US [117]. (Un)risky life habits, social climate and (un)balanced wealth more strongly influence fertility and perinatal outcome than absolute health care expenditures.

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After 1945, East Germany switched to a governmental health care with emphasis on prevention, social support and high fertility rates of younger women (Figure 2). In the West, health care was provided by

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a decentralized insurance system with modest parliamentary control, but privileges for physicians to self-regulate their performance. Women with the same cultural identity developed different behaviors all with an impact on maternal and fetal health. Surprisingly, there were no differences in outcome, but

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women in the East, were more satisfied with perinatal care where infant mortality rates were even lower in certain years [119]. Meanwhile, the Every Newborn Action Plan has underlined that the

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challenge to prevent neonatal death is not technical, but social [120]. Fertility and pregnancy are agedependent evolutionary processes that involve pre-and post-zygotic mechanisms. The replacement of the Eastern by the Western health care system in 1990 caused a dramatic decrease of fertility rates in young women [121] (Figure 2); health costs increased per hospital by 161% and per patient by 131%

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(1990-2000). The high rate of older mothers reflects the trend that reproduction and pregnancy care increasingly depend on expensive technical interventions, which may impact not only costs, but future genetics and epigenetics [122]. The Triple Aim of health care reforms: “better care, better population

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health, and lower per capita costs” [123], did obviously not guide the health care changes in Germany in 1990 nor in our present society.

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In many countries, only few lobbyists are more powerful than organized professional medical societies with self-protective policies [124]. The enormous budgets for health care have provoked potential for greed, fraud and abuse. It was estimated that misuse accounted for about 34% of all US health care spending in 2011 resulting in about $2.7 trillion [3]. In 2016, the German government asked the “Ethical Council” to write an extensive report about commercialized medicine [99] which may serve as an excuse not to control the quality of physician services (who vote).

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In Germany billing errors is at most not reimbursed if discovered; in other countries it is punished. German politics provides detailed statistics from all sorts of accidents or even harm to animals, but not

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about maternal deaths. A law establishing confidential inquiries, like that in the UK, would not create votes, but protect future maternal lives. As in the US, such prerogatives can raise the fears that avoiding legal controls can overrule civility.

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Perinatal care increasingly faces complex conditions and obstetricians with different working hours and behaviors. “Business as usual” shows a projection of health care costs growing faster than the GDP as

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opposed to fixing the percentage of GDP spent on health care. Targets between these lines within the triangle should ideally be eliminated (Figure 3). To overcome the cost explosion, D.M. Berwick has defined a new era to replace former protectionism and reductionism by “reducing mandatory measurement, stopping complex individual incentives, shifting the business strategy from revenue to

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quality, giving up professional prerogative when It hurts the whole, using improvement science, ensuring complete transparency, protecting civility, rejecting greed, and hearing the voices of the

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people served” [70]. Can we amplify the voices of fetuses and mothers?

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STAKEHOLDER AND POLITICAL LEVEL Pioneers have started to explore the fetal space “as if spacecrafts explored the universe” [125]. Fetuses

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are like planets defenseless, but easier to approach. Without doubt, there are colleagues who deserve respect for pioneering new forms of clinical care. Even more, the “obstetric art” should be analyzed to return human investments for more patients. Everyone can promote integration of research into

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everyday clinical practice. Regrettably, obstetric science is frequently a loosely organized endeavor, because too few intellectual obstetricians with management skills run obstetric units or are accepted

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as research managers. Physicians pass rigorous examinations to practice, clinical investigators do not. Governments or funding organizations rarely define academic research lines. Consequently, harms instead of benefits of an uncritical use of operations or medical therapies are revealed only after they occur rather than prevented by professionally responsible organizational leaders.

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A lack of team-work characterizes hierarchic systems with some princes in castles less motivated by ideals than by eagerness to be “the first or only”, to get high salaries or academic rewards instead of being “right” and a “team player”. Hundreds of biomarkers have been introduced for placental disease,

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prematurity or PE, many fetal surgery tools have been described, but only few have fulfilled the Triple Aim of cost reduction, public health improvement and patients’ satisfaction. The vicious circle of short-

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term views prevents the needed evaluation of these advances. In addition, research itself can sometimes be harmful. Based on horrific experiments of the Nazi time, the Nuremberg Code guided physician-investigators in experiments involving human subjects [126]. Biomedical research has to be in accordance with national requirements and ethical committees. Since "voluntary consent“ is a major regulatory criterion, research in MFM became ethically challenging: The fetus as a patient concept [127] is described in Chapter 12.

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In 2010, worldwide expenditure on life sciences research was $240 billion. In the US alone, about $70 billion in commercial and $40 billion in public and non-profit funding were spent annually, representing

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>5% of US health-care expenditure [128]. Key sources of avoidable waste were identified as a cumulative effect of about 85% of biomedical research investment, equating to $200 billion without considering inefficiencies in regulation and management [129]. A series of Lancet publications

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“increasing value, reducing waste” investigated weaknesses and proposed improvements relating to design, conduct, analysis, regulation and management of research, inaccessible information or

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incomplete or unusable reporting [121] [130-134]. The criteria also hold true for perinatal research and should be studied by researchers, funders and policy makers. Here, we can only summarize some aspects (Table 4).

Research money for MFM can also be lacking. A German government report stated that 80% of clinical

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scientists had limited contracts, many clinical obligations, reduced recognition and career chances [135]. The fact, that academic OBGYN chair positions can be obtained without research skills that academic chairs for MFM are not the standard, and that plagiarism of books is silently accepted creates

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vicious circles for the next obstetric generation to identify and prevent waste in research. Scandinavian countries with centralized social heath care have not only better perinatal outcome data,

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they also have adopted the policy that health is a public wealth and allow open access when matching perinatal data with life-long research in order to find answers with long-term consequences [41]. This represents responsible obstetric resource management. An example how low-income countries can teach “Perinatal Triple Aims” for high-income countries was the evaluation of kangarooing in the absence of neonatal intensive care units [136]. The data have

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revolutionized the behavior of Western neonatologists who had been dazzled by High-Tec and rediscovered High-Care. It showed that limited resources may incentivize creativity and humanity.

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Perinatal networks subsidized by public money mirror a careful research policy. In 2012, the Dutch network included >2500 patients according to pre-defined research protocols. The publications serve guidelines, insurances or policy makers and help young investigators to progress [137]. For complex

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syndromes and high-risk pregnancies, treatment in centers with multidisciplinary teams and scientific transparency has facilitated excellent European team-work [138-140].

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The CONSORT criteria are used by funding agencies interested in a return of fiscal investments. Policy makers need to better tackle long-term risks and inequities of perinatal care to improve effective planning [141]. Governments should support projects with potential human, not only commercial, benefits and be cautious with industry-sponsoring where clinicians only recruit. International ranking

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of scientific impact and improvement research should help policy makers to decide whether positions in professional societies, departments and advising committees are based on intellectual achievements to avoid wasting resources due to inappropriate research culture.

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In Stanford, children were offered a choice between one small reward (Marshmallow) provided immediately or several rewards if they waited. Those who were able to wait had many better health

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and educational outcomes in later life [142]. This insight is transferable to adults who are clinical investigators. Can policy makers understand and follow the allegory of the Stanford experiments?

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EDUCATIONAL LEVEL Hippocrates contemplated how to acquire medical knowledge, but not what it would cost. The purpose

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of medical education is to provide patients with competent physicians. The individual stakes of a resident, a medical school or department should be responsibly balanced against the social stakes of allowing an incompetent person to practice. Medical education should be structured, but should also

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allow space for reflection. The ROI of a good obstetric education is hard to objectify because enthusiastic obstetricians will strive for life-long learning and be invaluable for society, independent of

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their origin. Nevertheless, CEA models were used to link quality of care to training costs depending on administrators' willingness to pay per unit of the outcome variable [143]. The novel “House of God” fictionalized harm that may occur during residency [144]. A resident, who secretly did not follow rules, ironically became recognized by patients and the institution. Discovering

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what is wrong seemed equally conducive for patients and institutions, but was not openly discussed. By showing sad and funny behaviors within hierarchies, this provocative (and still read) book became a milestone for ethical discussions about medical training.

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Ethics is a core competency for obstetricians. A web-based survey assessed the status of ethics by asking U.S. program directors: 64% believed their residents were still unprepared to handle ethically

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challenging situations [145]. Another core competency is biostatistics to discriminate fact from fiction. Students learn that no method should be adopted unless it improves outcome, to have ideals and to think independently. The application process for residency can be professionalized by computerized systems matching residents to programs. Nevertheless, residents may enter the clinical arena with obstetricians who still regard clinical science as an enemy of pioneering or of copying books and with midwifes defending the mysteries of birth. If they follow these behaviors, their focus narrows, they

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become paralyzed and finally only lament: "I wasn't told" instead of “I have read” or: “I shall investigate”. This is waste of their previous studies. If exotic residents challenge the system, they are

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rarely supported by those who defend prerogatives. Intellectual capacities of the potentially most creative courageous ones are wasted when they stay or lost when they look for other places.

The German Bundes-Ärztekammer (BÄK, chamber of physicians) is responsible for (sub)specialists’

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training and evaluated postgraduate education in 2011. The survey compared the views of the faculty (n=17.392) with that of residents (n=53.126). Questionnaires were returned by 9.276 (53%) trainers

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and 20.218 (39%) residents. Only 14% of OBGYN residents reported that their training goals were planned and discussed, the department chairs contributed in 11% to their learning experience and faculty members estimated themselves to be significantly better than objectified by residents with maximal discrepancies in evidence-based medicine (Figure 4). The OBGYN results were the worst of all

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disciplines. Nevertheless, the President of the BÄK decided not to publish or discuss the data. According to cited criteria [130-134], the research money for this evaluation and chances for improvement were wasted and vicious circles continue.

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In many countries, training is organized with curricula and feed-back, regular audits of departments and certification procedures of training facilities. The European Board and College of OBGYN was

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founded to improve care by improving postgraduate training and the implementation of standards. Disparities in the quality of care and teaching show that there is much to learn from each other. International exchange is theoretically stimulated but rarely realized. Driven by the goals of the Triple Aim, there is a call for restructuring health professionals’ education and aligning it with the healthcare delivery system. The US Accreditation Council (CLER) now encourages the integration of leaders, faculty members, and residents in graduate medical education

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(GME) [146]. Options for improvement would be to involve statistics into postgraduate training. Economic situations and statistical methods continue to evolve (e.g. in genomics, metabolomics,

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prospective meta-analyses). Even those who do not become researchers need to assess publications relevant to clinical practice. External postgraduate lectures were shown to have significant impact on decision-making [147]. Internet programs can overcome local teaching deficits as demonstrated by

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lectures of professional societies (SMFM in the US, GYN-To-Go in Germany) or funders (Google Campus, Bill Gates Foundation). Teams and alliances within institutions, national or international

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communities can develop.

External team training has been shown to improve perinatal outcome [106]. A Cluster-RCT in Canada reduced Cesarean delivery rates (OR −1.7%; 95%CI−3.0 to −0.3; P=0.03) and major neonatal morbidity (OR −0.7%; 95%CI −1.3 to −0.1; P=0.03) in low-risk pregnancies by provision of feedback [148]. External

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team audits could help to transparently discuss economic and ethical dilemmas within departments, where health professionals are sensitive to be open. This would create education programs as part of the curriculum balancing interests of patients, residents, faculty, hospital managers and public health.

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With respect to the subspecialty of MFM, a US survey evaluated interest and satisfaction of residents: Only 90/642 (14%) of residents reported either ongoing consideration of, or having already applied for

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MFM training, while 278 (43%) had considered MFM training, but chose to either stay in general practice or pursue another fellowship; 274 (43%) reported never having considered MFM. Major factors influencing the pursuit of MFM training were the quality of educational experiences and encouragement. Conversely, the duration and the financial burden of the training program appeared to be significant deterrents [149].

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Oxygenated blood from the mother first passes the fetal heart before supplying the brain. Similarly, our highest hope for improvement within obstetrics and MFM lies in the hearts and brains of young

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residents –wherever they come from-- not frightened by the described burden. We cannot deny that even in modern times day and night shifts, efforts, or tears accompany the pathway to becoming a good obstetrician. MFM specialists should be humble and still be characterized by imagination,

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curiosity, courage and persistence. Experienced faculty members should stress the fascinating aspects of MFM so that residents deliberately tolerate the burden and should not let them be infected by the

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described vices. A pluralistic tolerant environment should support niches where Perinatal Triple Aims [123] or a Perinatal Era 3 [83] have a chance to flourish. Nevertheless, is the best obstetric training not wasted, if it is not continued by a daily will to improve as an individual, to improve the direct micro-

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cosmos, and to strive for improved perinatal care within the national and international community?

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SUMMARY AND CONCLUSIONS According to Greek mythology, Prometheus (forethought) and his brother, Epimetheus (afterthought)

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crafted the first creatures. The more thoughtful Prometheus imagined great things for human beings to accomplish and therefore stole the fire. One punishment of Zeus was the creation of Pandora as a wife for the more naïve Epimetheus, who opened the jar holding evils that spread over mankind. Only

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hope remained in the jar. Since then, the hope to understand mankind’s persisting mystery of pregnancy and birth has motivated obstetricians. Some of them experience the profession as a form of

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grace and hope to discern good from evil, believe in professional skills, ethics and research to accomplish benefits for patients or societies.

Can we be motivated by the hope to revitalize present and future responsibilities in favor of mothers

CONFLICT OF INTEREST:

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None

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and fetuses who cannot yet understand what happens and who might not be understood by others?

ACKNOWLEGEMENTS

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I thank Prof. F.A. Chervenak that he succeeded in persuading me to share my concerns by writing. I wish to express my gratitude to colleagues who sensitized me for certain aspects of the topic: Prof. G. Benagiano, Prof. D.E. Berwick, Prof. L. Mc Cullough, Prof. G. Gigerenzer, Prof. P. Unschuld.

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PRACTICE POINTS •

Human resource management, risk-benefit or cost-effective analyses accompany modern health care.

•

On the patient level, pre- and postnatal life style interventions, contraception, breastfeeding should be

•

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part of neutral information systems.

On the physician level, statistical knowledge, defensive medicine, overuse of low-value tests or treatments which cannot help or harm patients should be reconsidered.

On the institutional level, hygiene, safety and audit programs, team training and regular teaching moments should be better coordinated.

•

On the community level, administrative complexity and limited transparency should be changed using

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the Triple Aim for reforms and legal controls. •

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•

On the political level, short-term careers and expenditures for unbalanced research or projects which dominantly serve industries should be limited.

On the educational level, feed-back and a culture of life-long reflection should be emphasized.

RESEARCH AGENDA •

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•

Statistical models can be further developed to classify the usefulness of health care concepts and individual therapies.

Early patient education and factual shared decision programs should be introduced and evaluated.

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Professional, ethical and statistical skills should be promoted and examined.

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Institutions should evaluate computerized protocols and transparent interdisciplinary communication.

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Communities and governments could reduce bureaucracy, financial dominance, and corruption.

•

Politicians should scientifically (re)consider curricula of individuals in responsible positions at regular

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•

intervals, promote creative pilot programs and evidence-based long-term projects for mothers and offspring. •

In countries without training audits postgraduate curricula have to be designed and evaluated within an international context.

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World Health Report (2010) Background Paper, 30. Health Systems Financing, Geneva: World Health Organization, 2010. [93]. O'Neill SM, Agerbo E2, Kenny LC3, et al.: Cesarean section and rate of subsequent stillbirth, miscarriage, and ectopic pregnancy: a Danish register-based cohort study. PLoS Med. 2014 1;11(7): e1001670. [94]. Glasziou P, Haynes B: The paths from research to improved health outcomes. Evidence-based nursing 2005; 8(2):36-8. [95]. Ransom SB, Studdert DM, Dombrowski MP, et al.: Reduced medicolegal risk by compliance with obstetric clinical pathways: a case--control study. Obstet Gynecol 2003; 101(4):751-5. [96]. Risberg , B: Karolinska Ethik Tschernobyl (Karolinska--etikens-Tjernobyl). Available at: http://www.lakartidningen.se/Opinion/Debatt/2016/01/(last accessed 31/08/2016). [97]. Reddy UM, Abuhamad AZ, Levine D, Saade GR: Fetal imaging: Executive summary of a Joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine, American College of Obstetricians and Gynecologists, American College of Radiology, Society for Pediatric Radiology, and Society of Radiologists in Ultrasound Fetal Imaging Workshop. Am J Obstet Gnynecol 2014; 210(5):387-97. [98]. Bisognano M, Cherouny PH, Gullo S: Applying a science-based method to improve perinatal care: the institute for healthcare improvement perinatal improvement community. Obstet Ggynecol 2014; 124(4):810-4. [99]. Deutscher Ethikrat: Patientenwohl als ethischer Maßstab für das Krankenhaus. Available at: http://www.ethikrat.org (last accessed 31/08/2016). [100]. Devereaux PJ, Choi PT, Lacchetti C, et al.: A systematic review and meta-analysis of studies comparing mortality rates of private for-profit and private not-for-profit hospitals. CMA: Canadian Medical Association journal 2002; 166(11):1399-406. [101]. Collins J: Good to Great: Why Some Companies Make the Leap...And Others Don't. New Yorck: HarperCollins; 2001. [102]. Unschuld P: Ware Gesundheit - das Ende der klassischen Medizin, vol. 3. München: C.H.Beck Verlag 2014. [103]. Pittet D, Sax H, Hugonnet S, Harbarth S: Cost implications of successful hand hygiene promotion. Infect ContrHospit Epidemiol 2004; 25(3):264-6. [104]. Allegranzi B, Gayet-Ageron A, Damani N, et al.: Global implementation of WHO's multimodal strategy for improvement of hand hygiene: a quasi-experimental study. Lancet Infectious diseases 2013; 13(10):843-51. [105]. Laufer FN, Warren BL, Pulver WP, et al.: Return on Investment From Expenditures Incurred to Eliminate Mother-To-Child Transmission Among HIV-Infected Women in New York State: 1998-2013. J Acquir Immune Defic Syndr 2016; 71(5):558-62. [106]. Siassakos D, Crofts JF, Winter C, et al.: The active components of effective training in obstetric emergencies. BJOG 2009; 116(8):1028-32. [107]. DeStephano CC, Chou B, Patel S, et al.: A randomized controlled trial of birth simulation for medical students. Am J Obstet Gynecol 2015; 213(1):91e91-7. [108]. Merien AE, van de Ven J, Mol BW, et al.: Multidisciplinary team training in a simulation setting for acute obstetric emergencies: a systematic review. Obstet Gynecol 2010; 115(5):1021-31.

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[109]. van de Ven J, Houterman S, Steinweg RA, et al.: Reducing errors in health care: costeffectiveness of multidisciplinary team training in obstetric emergencies (TOSTI study); a randomised controlled trial. BMC pregnancy and childbirth 2010; 10:59. [110]. van Diem MT, Timmer A, Gordijn SJ, et al.: Classification of substandard factors in perinatal care: development and multidisciplinary inter-rater agreement of the Groningen-system. BMC pregnancy and childbirth 2015; 15:215. [111]. Eskes M, Waelput AJ, Erwich JJ, et al.: Term perinatal mortality audit in the Netherlands 20102012: a population-based cohort study. BMJ open 2014; 4(10):e005652. [112]. Pettker CM, Grobman WA: Obstetric Safety and Quality. Obstet Gynecol 2015; 126(1):196-206. [113]. Donovan EF, Lannon C, Bailit J, et al.: A statewide initiative to reduce inappropriate scheduled births at 36(0/7)-38(6/7) weeks' gestation. Am J Obstet Gynecology 2010; 202(3):243 e241-248. [114]. Nielsen PE, Goldman MB, Mann S, et al.: Effects of teamwork training on adverse outcomes and process of care in labor and delivery: a randomized controlled trial. Obstet Gynecol 2007; 109(1):4855. [115]. Sciscione A, Berghella V, Blackwell S, et al.: Society for maternal-fetal medicine (SMFM) special report: the maternal-fetal medicine subspecialists' role within a health care system. Am J Obstet Gynecol 2014; 211(6):607-16. [116]. ABIM Foundation. Choosing Wisely. Available at: http://www.choosingwisely. orgethikrat.org /(last accessed 31/08/2016). [117. OECDList-of-variables-OECD-Health-Statistics-2015 Available at: http://www.oecd.org (last accessed 31/08/2016). [118]. Lagrew DC, Jr., Jenkins TR: The future of obstetrics/gynecology in 2020: a clearer vision. Transformational forces and thriving in the new system. Am J Obstet Gynecol 2015; 212(1):28-33 e21. [119]. Arabin B, Raum E, Mohnhaupt A, Schwartz FW: Two types of health care systems and their influence on the introduction of perinatal care: an epidemiological twin model in Berlin from 1950 to 1990. Mat Child Health J 1999; 3(2):81-91. [120]. Every newborn, every mother, every adolescent girl. Lancet 2014; 383(9919):755. [121]. Pötzsch O: Deliveries in Germany. Wiesbaden: Statistical Office of Germany 2012. [122. Hanevik HI, Hessen DO, Sunde A, Breivik J: Can IVF influence human evolution? Hum Reprod 2016; 31(7):1397-402. [123].* Berwick DM, Nolan TW, Whittington J: The triple aim: care, health, and cost Health Aff (Millwood) 2008; 27:759–69. [124]. Berwick DM: The toxic politics of health care. Jama 2013; 310(18):1921-2. [125]. Saling E, Arabin B: Historic landmarks of perinatal medicine in obstetrics. J Perinat Med 1988; 16(1):5-21. [126]. Katz J: The Nuremberg Code and the Nuremberg Trial. A reappraisal. Jama 1996; 276(20):16626. [127]. Chervenak FA, McCullough LB: Ethics of research in perinatal medicine. Seminars Perinat 2009; 33(6):391-6. [128]. Rottingen JA, Regmi S, Eide M, et al.: Mapping of available health research and development data: what's there, what's missing, and what role is there for a global observatory? Lancet 2013; 382(9900):1286-1307. [129].* Chalmers I, Glasziou P: Avoidable waste in the production and reporting of research evidence. Lancet 2009; 374(9683):86-9.

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[130]. Glasziou P, Altman DG, Bossuyt P, et al.: Reducing waste from incomplete or unusable reports of biomedical research. Lancet 2014, 383(9913):267-76. [131]. Ioannidis JP, Greenland S, Hlatky MA, et al.: Increasing value and reducing waste in research design, conduct, and analysis. Lancet 2014, 383(9912):166-75. [132]. Al-Shahi Salman R, Beller E, Kagan J, et al.: Increasing value and reducing waste in biomedical research regulation and management. Lancet 2014, 383(9912):176-85. [133]. Chan AW, Song F, Vickers A: Increasing value and reducing waste: addressing inaccessible research. Lancet 2014, 383(9913):257-66. [134]. Macleod MR, Michie S, Roberts I, et al.: Biomedical research: increasing value, reducing waste. Lancet 2014, 383(9912):101-4. [135]. IGES: Daten und Analysen. Available at: http//www.iges.de (last accessed 31/08/2016). [136]. Conde-Agudelo A, Diaz-Rossello JL: Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane database Systemat Rev 2016; 8:CD002771. [137]. Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynecology. Available at: http//www.obsgyn.nl/ (last accessed 31/08/2016). [138]. Senat MV, Deprest J, Boulvain M, et al.: Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. NEJM 2004; 351(2):136-44. [139]. van Klink JM, Slaghekke F, Balestriero MA, et al.: Neurodevelopmental outcome at 2 years in twin-twin transfusion syndrome survivors randomized for the Solomon trial. Am J Obstet Gynecol 2016; 214(1):113 e111-7. [140]. Lees CC, Marlow N, van Wassenaer-Leemhuis A, Arabin B, et al. : 2 year neurodevelopmental and intermediate perinatal outcomes in infants with very preterm fetal growth restriction (TRUFFLE): a randomised trial. Lancet 2015; 385(9983):2162-72. [141]. Armstrong R, Waters E, Moore L, et al.: Improving the reporting of public health intervention research: advancing TREND and CONSORT. J Public Health (Oxf) 2008, 30(1):103-9. [142]. Mischel W, Shoda Y, Rodriguez MI: Delay of gratification in children. Science 1989; 244(4907):933-8. 143]. Tolsgaard MG, Tabor A, Madsen ME, et al.: Linking quality of care and training costs: costeffectiveness in health professions education. Med Educat 2015; 49(12):1263-71. [144]. Shem S: The House of God. London Black Swan Transwold Publishers 1978. 145]. Byrne J, Straub H, DiGiovanni L, Chor J: Evaluation of ethics education in obstetrics and gynecology residency programs. Am J Obstet Gynecol 2015; 212(3):397 e391-8. [146]. Wehbe-Janek H, Markova T, Polis RL, et al.: Preparing Academic Medical Centers for the Clinical Learning Environment Review: Alliance of Independent Academic Medical Centers National Initiative IV Outcomes and Evaluation. The Ochsner journal 2016, 16(2):166-1. [147]. Norwitz ER, Bahtiyar MO, Sibai BM: Can postgraduate courses in Maternal-Fetal Medicine change clinical attitude? J Mat Fet Neonat 2005; 18(5):311-7. [148]. Chaillet N, Dumont A, Abrahamowicz M, et al.: A cluster-randomized trial to reduce cesarean delivery rates in Quebec. NEJM 2015; 372(18):1710-21. [149]. Lu G, Owen J, Wenstrom K: Obstetrics and gynecology residents' attitudes toward maternalfetal medicine fellowship training. J Mat Fet Neonat 2004, 16(5):259-63. [150]. Gotzsche PC, Jorgensen KJ: Screening for breast cancer with mammography. Cochrane database Systemat Rev 2013; 6:CD001877.

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days

2007 2008 2009 2010 2011 2012 2013 2014

1872 2157 2455 3154 3147 2763 2799 2923

Observed average patient days

Difference in outbreak patient

Difference in outbreak costs

(€)

days

1872 330 1248 5285 1285 1505 2679 1211

– 1826 1207 -2131 1862 1258 120 1712

– 958,912 633,520 -1,118,736 977,749 660,660 62,756 898,711

Incremental rise infection prevention budget

(€)

Difference infection prevention costs

ROI

(€)

– 134,049 195,515 138,130 191,843 115,491 222,046 110,526

– 782,341 409,912 -1,207,257 742,549 515,873 -162,072 748,333

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Predicted outbreak patient

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YEAR

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39

– 5.84 2.10 -8.74 3.87 4.47 -0.73 6.77

Table 1) Example for the evaluation of return on investment (ROI) by hygiene efforts within a

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Dutch Academic Medical Center during years with increasing colonization rates and costs for hygiene. 2007 was defined as YEAR ZERO, 2010 was characterized by an outbreak. The ROI is calculated from the difference of predicted/factual costs.

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Source: van Dik et al, 2016 [23]

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1000 women without screening

1000 women with screening

5 21 84

Harms How many women without cancer experienced false alarms or biopsies? How many women with non-.progressive cancer had unnecessary partial or complete removal?

-

4 21 84

50-200

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How many women died from breast cancer? How many women died from all types of cancer? How many women died from any cause?

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Benefits

2-10

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Table 2) Example of a fact box to explain the use of mammography screening to patients: Numbers for women aged 50 years or older who did or did not participate in screening for about 10 years. Although mammography screening may reduce the number of women who die from breast cancer, it does not mean that lives are saved: there was no reduction of overall mortality and cancer deaths. In

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women with screening, some will be overdiagnosed with non-progressive cancer and unnecessarily treated. Similar boxes will be co-operatively designed in the future for obstetric situations.

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Numbers are rounded, where no data for women> 50 years are available, numbers refer to women > 40 years, last updated: December 2015.

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Source: Gigerenzer 2016 [17], based on Gotzsche and Jorgensen, 2013 [148]

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Birth

1604

515

Obstetrics Abortion

1569 386

561 69

Perinatal Medicine

313

86

Maternal Mortality

325

122

Preterm birth

282

92

Perinatal Mortality

178

40

Breastfeeding

176

59

GDM

117

49

Maternal-fetal Medicine Pre-eclampsia

146

51

73

29

Obesity during pregnancy

45

25

Twin pregnancy

41

10

Education Teaching obstetrics

166

71

130

55

27

19

14

5

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Education of obstetrics Postgraduate education Perinatal Audits

2011-16

CEA/interventions

All

2011-16

645

175

2509

582

210

59

General pregnancy treatment Contraception

519

103

117 70

14 35

Cesarean Hospitalization

261 205

62 35

60

26

Tocolytics

185

34

44

19

Patient information

123

46

43

18

112

14

34

14

Antibiotics during pregnancy Induction of labor

98

24

Lifestyle interventions during pregnancy Corticosteroids for lung maturity

40

18

25

4

RI PT

2079

All

SC

6830

CEA/screening and diagnosis Routine pregnancy screening Abdominal Ultrasound Amniocentesis Screening for GDM Transvaginal Ultrasound Screening for toxoplasmosis Screening for preterm birth Screening for cytomegaly Chorionic villous sampling Screening for pre-eclampsia Screening for thallasemia Screening for spina bifida Screening for developmental hip dysplasia Non-invasive genetic testing Fibronectin Screening for FHD

M AN U

2011-16

32

15

32

15

32

12

Vaginal Progesterone to prevent SPB

20

12

20

1

Aspirin

13

4

14

3

Interventions for Obesity

10

7

12

9

Cerclage

9

3

9 9

5 2

8 9

3 1

Non-invasive fetal 8 RhD genotyping Cell-free D N A for 6 trisomy 21 Screening for 1 vasa previa

6

OHPC to prevent SPB Antihypertensive drugs Metformin

7

4

6

Cervical Pessary

5

1

-

Interpregnancy care

0

0

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All

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CEA/general obstetric terms Delivery

Table 3) Overview about a selection of existing studies (numbers found by mesh terms and secondary selection) related to cost-effective analysis (CEA) combined with general obstetric terms, education, screening or diagnosis and obstetric interventions (retrieved until 31-7-2016), separated for total and recent years (2011-2016) to see rising or decreasing trends. FHD=fetal heart defects, GDM=gestational diabetes, OHPC= 17-alpha hydroxyprogesterone caproate

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Use of information, precision, power, outcomes

Statistical power and outcome misconceptions

Replication and repeatability

Insufficient consideration of other evidence

Consideration of evidence

Subjective, non-standardized definitions, vibration of effects

Minimize influence of potential conflicts, reproducibility and reward systems

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Poor utility of information

Recommendations for policy makers Research regulators should reduce waste and inefficiency by regulating, monitoring, and measuring to which extent research complies with recommendations. Policy makers should work with researchers, patients, and health professionals to streamline and harmonize laws and guidelines that ensure that they are proportionate to the plausible risks and should report delays and inconsistencies that result from failure to streamline. Research managers should increase recruitment, data monitoring, and data sharing in research and learn how efficiency can be increased.

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Options for improvement Protocols and documentation

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Problems of clinical research Poor protocols and designs

Individuals responsible for health-care systems can help to improve efficient clinical research by promoting integration in everyday practice.

Table 4) Some selected proposals for clinicians and policy makers how to avoid research waste:

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“Increasing value, reducing waste”.

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Source: 5 publications in the Lancet [128-132]

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LEGENDS FOR FIGURES Figure 1) Threshold number of women needed to receive aspirin prophylaxis to prevent one case of

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pre-eclampsia, based on individual clinical risk factors determined by 16 weeks’ gestation. Dashed line is the number to prevent (NNPt) of 250 women calculated from a huge data base, assuming a conservative 10% or 30% and 50% relative risk reduction (RRR).

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Source: Bartsch et al., 2016 [21]

IUGR= intrauterine growth restriction; SLE=systematic lupus erythematosus; ART=assisted reproductive

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technology; BMI=body mass index; aPL=antiphospholipid antibody syndrome

Figure 2) Mean number of deliveries / 1000 women stratified according to different age groups and West (left) or East (right) Germany from 1975 until 2010. In the East, there was a high rate of mothers

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between 20 and 30 years compared to the West, followed by a dramatic decrease of deliveries in the period of the reunification and a consecutive increase of women delivering at older age comparable to other high-income countries.

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Source: Office of German statistics, Wiesbaden, 2012 [119].

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Figure 3) Proposed “Wedges” Model for US Health Care with spending reduction targets for categories of waste: Upper rising line: projection of health care spending following “business as usual”, lower stable line: expenditures for national health care match with gross domestic product (GDP). The regions filling the triangle between the lines show spending reduction targets. Source: Berwick and Hackbarth, 2012 [3]

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Figure 4) Spiders demonstrating answers of German residents in training for Obstetrics and Gynecology (OBGYN) 2011 related to(clockwise) general experience (top), experienced competency, culture of

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learning, leadership culture, culture around errors, decision, organization and finally (the worst) the application of science and evidence-based medicine.

Based on a countrywide survey of residents and faculty members, answers from 403 units of obstetrics

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and gynecology were integrated. The numbers represent German school grades from 1 (excellent), 2 (good), 3 (satisfying) 4 (less than mediocre) 5 (bad) 6 (unacceptable).

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The fat line represents answers of residents, the dotted line answers of teachers. Discrepancies between teachers and residents limit chances for improvement.

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Source: Data from the German chamber of physicians (Bundes-Ärztekammer)

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HIGHLIGHTS

• In high-income countries, high budgets may lead to overuse in health care and to

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unnecessary risks for mothers and infants. Options for improvement can be created at different levels of health care systems.

long-term life quality of mothers and their infants.

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• Definitions of calculations exist as models regarding health care costs for survival and

• Health literacy is an essential issue for the future of maternal-fetal medicine.

and of health care managers.

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• Responsible resource management also implies knowledge and ethics of physicians

• Research including improvement statistics should be implied into daily practice without wasting money for useless projects. Postgraduate training should be an issue

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of concern stimulating lifelong curiosity and learning.

• Health care reforms in maternal-fetal medicine should follow the Triple Aim of

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improving patient satisfaction, health of society and reducing costs.