Comparative effectiveness is the common denominator in health services research: experimental effects are promising, real-world effects are compelling.

BACKGROUND: Sir Archibald Cochrane and Sir Austin Bradford Hill requested 80 years ago answers to three questions (Can it work? Does it work? Is it worth it?) before a new intervention is implemented in day-to-day healthcare. A critical analysis of currently accepted answers identified a terminology conflict that inherits the risk of misleading interpretations and inappropriate decisions. CONTENT: For detection of the terminology problem and the development of the solutions was possible through three recommendations (the "Ulm heritage"): (1) Albert Einstein (*1879 in Ulm/Germany) predicted, "A problem cannot be solved with the way of thinking that caused it"; (2) The "hochschule für gestaltung ulm (Academy of Design, 1953-1968)" disseminated the rules of American designers and architects e.g., "Form Follows Function"; and (3) requested to "design not only individual but universally valid solutions with socio-political relevance". SUMMARY: Our data confirms the power of the FFF rule, the pros and cons of value judgments, the complexity of healthcare decisions, the difference between scientific statements and political decisions, and the effects of interprofessional collaboration. OUTLOOK: "Efficacy" offers promising "Proofs of Principle (PoP)" while "effectiveness" describes "Real-World Effectiveness (RWE)". That is why the results obtained are always more important than hypotheses.

[Covid-19: Twin Method for Verifying Real-World Effectiveness Under Everyday Conditions]. / Covid-19: Twinmethode zum Nachweis der Real-World Effectiveness (RWE) unter Alltagsbedingungen.

The positive side of the Covid-19 pandemic is that it has provided a stimulation for innovations. As an example, we discuss the Pragmatic Controlled Trial (PCT), a twin study that can be used to confirm the real-world effectiveness (RWE) of health services under the non-standardized conditions of everyday care. Proof of the RWE could generally be important for health services with conditional approval. The PCT uses the Bayesian principle instead of randomization. It enables care under non-standardized everyday conditions and, by describing the endpoint-specific risks of each individual patient and by classifying the interventions, creates an unbiased evaluation in a non-experimental, but risk-stratified and controlled study. Patients expect a timely solution to their health problems. Until now, science has required sufficiently well-founded results before approving an innovation. The Covid-19 pandemic has shown that the demand for immediate and best possible care can be met through the conditional approval of a new care principle. With the PCT, we describe a procedure with which, after conditional approval, the missing data can be collected in order to successfully complete the approval process.

Measuring Health-Related Quality of Life in Randomised Controlled Trials: Expected and Reported Results Do Not Match.

Purpose: The assessment of health-related quality of life (hrQoL) may need to be reconsidered due to important differences between efficacy (the effect of a treatment under experimental study conditions) and effectiveness (the effect of a treatment under real-world conditions). We presume that most researchers intend to describe effects under real-world conditions when investigating hrQoL as an endpoint. Unfortunately, most studies are designed to confirm two theories: the efficacy of a new intervention under experimental study conditions and the real-world effectiveness of this intervention on hrQoL under non-experimental study conditions. Conflicting information emerges when the outcomes are supposed to describe effects under real-world conditions, but the assessment generates results obtained under experimental conditions. This paper examines the existing conflict between efficacy and effectiveness in a sample of 100 studies investigating hrQoL. Methods: We analysed a sample of freely available publications of clinical studies listed in PubMed between April 2015 and August 2016 which assessed quality of life as an outcome. We assessed the following four characteristics that should differ in studies measuring either efficacy or effectiveness: 1) specification of the study as a randomised controlled trial or not, 2) description of the study design as pragmatic or not, 3) classification of the study as an efficacy or an effectiveness study and 4) number of selected inclusion and exclusion criteria. Results: 91% of the studies assessed hrQoL under experimental conditions (in a randomised controlled trial), but not under real-world conditions. The important difference between efficacy and effectiveness was not described in 60% of the studies. Only 6% of studies classified the study as a pragmatic trial. The difference between inclusion and exclusion criteria was not addressed in any of the investigated studies. Conclusion: The results of the four criteria confirmed our hypothesis that hrQoL studies are conducted mainly as experimental, but not pragmatic, trials indicating that the meaningfulness of the important difference between efficacy and effectiveness requires further discussion. Keywords: pragmatic trial, experimental study conditions, real-world conditions, efficacy, effectiveness, pragmatic.

Percepções dos profissionais de saúde sobre conceitos de economia clínica e advogado do paciente / Percepciones de profesionales de la salud sobre los conceptos de economía clínica y abogado del paciente / Perceptions of health professionals on concepts clinical economics and patient advocate

Objetivo: compreender a perspectiva dos profissionais de saúde sobre os conceitos de Economia Clínica e Advocacia do Paciente. Método: estudo qualitativo com profissionais de saúde. Os dados foram coletados em junho/2017 a partir da questão: Qual a sua percepção sobre o conceito de Economia Clínica e Advocacia do Paciente? Os dados qualitativos foram analisados pelo Discurso do Sujeito Coletivo. Resultados: os discursos apontaram que se trata de propostas inovadoras, desafiadoras e aplicáveis para a enfermagem e a saúde. O Advogado do Paciente e o conceito de Economia Clínica podem subsidiar as decisões dos gestores da equipe/serviços de saúde. As ideias podem potencializar a integração das equipes, solucionar conflitos, aproximar diferentes categorias profissionais e mitigar os riscos de responsabilidades legais, financeiras e éticas em relação à assistência à saúde. Conclusão: os conceitos foram entendidos como fundamentais e aplicáveis, uma vez que as organizações sobrevivem com adequada gestão humana, financeira e material.

Objetivo: comprender la perspectiva de los profesionales de la salud sobre los conceptos de Economía Clínica y Defensa del Paciente. Método: estudio cualitativo con profesionales de la salud. Los datos fueron recolectados en junio/2017 a partir de la pregunta: ¿Cuál es su percepción del concepto de Economía Clínica y Defensa del Paciente? Los datos cualitativos fueron analizados utilizando el Discurso del Sujeto Colectivo. Resultados: los discursos indicaron que se trata de propuestas innovadoras, desafiantes y aplicables para la enfermería y la salud. El Defensor del Paciente y el concepto de Economía Clínica pueden apoyar las decisiones de los gestores de equipos/servicios de salud. Las ideas pueden mejorar la integración del equipo, resolver conflictos, unir diferentes categorías profesionales y mitigar los riesgos de las responsabilidades legales, financieras y éticas en relación con la atención de la salud. Conclusión: los conceptos fueron entendidos como fundamentales y aplicables, ya que las organizaciones sobreviven con una adecuada gestión humana, financiera y material.

Objective: to understand the perspective of health professionals on the concepts of Clinical Economics and Patient Advocate. Method: a qualitative study with health professionals. Data were collected in June/2017 from the question: What is your perception of the concept of Clinical Economics and Patient Advocate? Qualitative data were analyzed using the Collective Subject Discourse. Results: the speeches pointed out that it deals with innovative, challenging and applicable proposals for nursing and health care. Patient Advocate and the Clinical Economics concept can support the decisions of the health team/service managers. The ideas can enhance the integration of the teams, resolve conflicts, bring together different professional categories and mitigate the risks of legal, financial and ethical responsibilities regarding health care. Conclusion: the concepts was understood as fundamental and applicable, since the organization survive with adequate human, financial and material management.

Covid-19 pandemic lessons: uncritical communication of test results can induce more harm than benefit and raises questions on standardized quality criteria for communication and liability.

BACKGROUND: The COVID-19 pandemic is characterized by both health and economic risks. A 'safety loop' model postulates risk-related decisions are not based on objective and measurable risks but on the subjective perception of those risks. We here illustrate a quantification of the difference between objective and subjective risks. METHOD: The objective risks (or chances) can be obtained from traditional 2 × 2 tables by calculating the positive (+LR) and negative (-LR) likelihood ratios. The subjective perception of objective risks is calculated from the same 2 × 2 tables by exchanging the X- and Y-axes. The traditional 2 × 2 table starts with the hypothesis, uses a test and a gold standard to confirm or exclude the investigated condition. The 2 × 2 table with inverted axes starts with the communication of a test result and presumes that the communication of bad news (whether right or false) will induce 'Perceived Anxiety' while good news will induce 'Perceived Safety'. Two different functions (confirmation and exclusion) of both perceptions (Perceived Anxiety and Safety) can be quantified with those calculations. RESULTS: The analysis of six published tests and of one incompletely reported test on COVID-19 polymerase chain reactions (completed by four assumptions on high and low sensitivities and specificities) demonstrated that none of these tests induces 'Perceived Safety'. Eight of the ten tests confirmed the induction of 'Perceived Anxiety' with + LRs (range 3.1-5900). In two of these eight tests, a -LR (0.25 and 0.004) excluded the induction of 'Perceived Safety'. CONCLUSIONS: Communication of test results caused perceived anxiety but not perceived safety in 80% of the investigated tests. Medical tests - whether true or false - generate strong psychological messages. In the case of COVID-19 tests may induce more perceived anxiety than safety. Risk communication has to balance objective and subjective risks.

Efficacy and effectiveness studies of depression are not well-differentiated in the literature: a systematic review.

BACKGROUND: In the literature on the treatment of depression, efficacy and effectiveness research have different purposes and should apply different research methodologies. OBJECTIVE: The purpose of the study was to review characteristics of depression treatment studies identified using efficacy or effectiveness search terms. We considered subject inclusion and exclusion criteria; numbers of subjects enrolled and the proportion in the primary analyses; inclusion of a Consolidated Standards of Reporting Trials (CONSORT) flow diagram; use of random assignment; use of placebo control conditions; lengths of treatment and follow-up; primary outcome variable; trial registration; journal impact factor. STUDY SELECTION: Studies indexed as efficacy AND 'real-world' AND depression or effectiveness AND 'real-world' AND depression in PubMed up to 18 May 2019. FINDINGS: 27 studies met the inclusion criteria: 13 effectiveness studies, 6 efficacy studies and 8 studies indexed as both effectiveness and efficacy. Studies identified as effectiveness, efficacy, or both differed on three outcome measures: the inclusion criteria were lengthier for efficacy than for effectiveness studies; efficacy studies were more likely to have a placebo control condition than effectiveness studies; and the journal impact factor was lower for effectiveness studies than for studies from the efficacy search or studies identified by both searches. CONCLUSIONS: Efficacy and effectiveness research hypothetically use different methodologies, but the efficacy and effectiveness literatures in the treatment of depression were comparable for most of the coded characteristics. The lack of distinguishable characteristics suggests that variably applied terminology may hinder efforts to narrow the gap between research and practice. PROSPERO REGISTRATION NUMBER: #CRD42019136840.

The terminology conflict on efficacy and effectiveness in healthcare.

Designers and architects created the rule 'form follows function (FFF)' for their own profession. Our paper demonstrates that this FFF rule applies equally well to the designers of clinical studies. Four examples present are as follows: disregarding this FFF rule causes an inconsistent terminology to differentiate between efficacy and effectiveness, inconsistent differentiation of efficacy and effectiveness interferes with the consistent interpretation of the results of clinical studies, inconsistent interpretation of clinical studies results in an unexpectedly variance of recommendations in clinical guidelines and the fusion of the FFF designer rule and of the demands of Cochrane and Bradford Hill ('can it work?', 'does it work?' and 'is it worth it?') avoids the terminology problem and its misleading consequences. This strategy is presented.

Recommendations for cancer screening would be different if we measured endpoints that are valid, reliable, specific, and important to patients.

BACKGROUND: Despite enthusiasm for cancer screening, systematic reviews consistently fail to show that screening reduces all-cause mortality. This narrative review explores conceptual issues, and inconsistencies between evidence and opinion about screening. REVIEW: We examined the interpretation of screening studies in relation to three intellectual traditions: (1) The relationship between prevention and cure; (2) Confirmation bias and the challenge of incorporating new data: less care may produce better outcomes than more care; (3) The answers to three structured questions about efficacy, effectiveness, and value of treatments proposed by Sir Archie Cochrane and Sir Austin Bradford Hill. SYNTHESIS: When considering extensions of life expectancy or all-cause mortality, systematic reviews typically show cancer screening to have only small effects and often non-significant effects on all-cause mortality. Early diagnosis does not assure application of an intervention that alters the pathway toward demise. The interpretation of screening results is also affected by several known biases. Investigators and advocates are encumbered by an over focus on studies designed to determine if a treatment can work under ideal circumstances. To advance the field, we need a greater emphasis on evaluations that ask 'Does the treatment work under real-world conditions?', and 'Is the treatment worth it?' in terms of outcomes that are meaningful to patients.

End-of-life perceptions among physicians in intensive care units managed by anesthesiologists in Germany: a survey about structure, current implementation and deficits.

BACKGROUND: Structural aspects and current practice about end-of-life (EOL) decisions in German intensive care units (ICUs) managed by anesthesiologists are unknown. A survey among intensive care anesthesiologists has been conducted to explore current practice, barriers and opinions on EOL decisions in ICU. METHODS: In November 2015, all members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthesiologists (BDA) were asked to participate in an online survey to rate the presence or absence and the importance of 50 items. Answers were grouped into three categories considering implementation and relevance: Category 1 reflects high implementation and high relevance, Category 2 low and low, and Category 3 low and high. RESULTS: Five-hundred and forty-one anesthesiologists responded. Only four items reached ≥90% agreement as being performed "yes, always" or "mostly", and 29 items were rated "very" or "more important". A profound discrepancy between current practice and attributed importance was revealed. Twenty-eight items attributed to Category 1, six to Category 2 and sixteen to Category 3. Items characterizing the most urgent need for improvement (Category 3) referred to patient outcome data, preparation of health care directives and interdisciplinary discussion, standard operating procedures, implementation of practical instructions and inclusion of nursing staff and families in the process. CONCLUSION: The present survey affirms an urgent need for improvement in EOL practice in German ICUs focusing on advanced care planning, distinct aspects of changing goals of care, implementation of standard operating procedures, continuing education and reporting of outcome data.

Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines.

BACKGROUND AND AIMS: Liver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of HCC with and without underlying cirrhosis. METHODS: We compared the following guidelines published after 1 January 2010: American (American Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola de Oncologia Medica (SEOM)), European (European Association for the study of liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and European Society for Medical Oncology-European Society of Digestive Oncology (ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)), Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana Oncologia Medica (AIOM)) and German (S3) guidelines. RESULTS: All guidelines recommend resection as therapy of choice in healthy liver. Guidelines based on the Barcelona Clinic Liver Cancer staging system recommend resection for single HCC<2 cm and Child-Pugh A cirrhosis and for HCC≤5 cm with normal bilirubin and portal pressure, whereas transplantation is recommended for multiple tumours between Milan criteria and for single tumours ≤5 cm and advanced liver dysfunction. Patients with HCC and Child-Pugh C cirrhosis are not candidates for transplantation. JSH guidelines recommend LR for patients with Child-Pugh A/B with HCC without tumour size restriction; APASL guidelines in general exclude patients with Child-Pugh A from transplantation. In patients with Child-Pugh B, transplantation is the second-line therapy, if resection is not possible for patients within Milan criteria. German and Italian guidelines recommend transplantation for all patients within Milan criteria. CONCLUSIONS: Whereas resection is the standard therapy of HCC in healthy liver, a standard regarding the indication for LR and transplantation for HCC in cirrhotic liver does not exist, although nearly all guidelines claim to be evidence based. Surprisingly, despite European guidelines, Germany and Italy use their own national guidelines which partially differ from the European. Possible solutions of the problems are discussed.

Major discrepancies between what clinical trial registries record and paediatric randomised controlled trials publish.

BACKGROUND: Whether information from clinical trial registries (CTRs) and published randomised controlled trial (RCTs) differs remains unknown. Knowing more about discrepancies should alert those who rely on RCTs for medical decision-making to possible dissemination or reporting bias. To provide help in critically appraising research relevant for clinical practice we sought possible discrepancies between what CTRs record and paediatric RCTs actually publish. For this purpose, after identifying six reporting domains including funding, design, and outcomes, we collected data from 20 consecutive RCTs published in a widely read peer-reviewed paediatric journal and cross-checked reported features with those in the corresponding CTRs. METHODS: We collected data for 20 unselected, consecutive paediatric RCTs published in a widely read peer-reviewed journal from July to November 2013. To assess discrepancies, two reviewers identified and scored six reporting domains: funding and conflict of interests; sample size, inclusion and exclusion criteria or crossover; primary and secondary outcomes, early study completion, and main outcome reporting. After applying the Critical Appraisal Skills Programme (CASP) checklist, five reviewer pairs cross-checked CTRs and matching RCTs, then mapped and coded the reporting domains and scored combined discrepancy as low, medium and high. RESULTS: The 20 RCTs were registered in five different CTRs. Even though the 20 RCTs fulfilled the CASP general criteria for assessing internal validity, 19 clinical trials had medium or high combined discrepancy scores for what the 20 RCTs reported and the matched five CTRs stated. All 20 RCTs selectively reported or failed to report main outcomes, 9 had discrepancies in declaring sponsorship, 8 discrepancies in the sample size, 9 failed to respect inclusion or exclusion criteria, 11 downgraded or modified primary outcome or upgraded secondary outcomes, and 13 completed early without justification. The CTRs for seven trials failed to index automatically the URL address or the RCT reference, and for 12 recorded RCT details, but the authors failed to report the results. CONCLUSIONS: Major discrepancies between what CTRs record and paediatric RCTs publish raise concern about what clinical trials conclude. Our findings should make clinicians, who rely on RCT results for medical decision-making, aware of dissemination or reporting bias. Trialists need to bring CTR data and reported protocols into line with published data.

[Prevention must become more efficient]. / Prävention muss effizienter werden.

The term "prevention" is used with several different meanings. Mistakes can be avoided by using different word for different contents. In addition to clear definitions the most frequent forms of bias have to be avoided. These forms are related to the five dimensions such as targets and endpoints as well as methods of screening, diagnostic, and finally treatment. Unless the appropriate items are selected in all five dimensions the results of the prevention strategy will not provide valid information.

The analysis of factors affecting municipal employees' willingness to report to work during an influenza pandemic by means of the extended parallel process model (EPPM).

BACKGROUND: The management of pandemics with highly infectious diseases in modern urban habitats depends largely on the maintenance of public services. Understanding the factors that influence municipal employees' willingness to come to work during a pandemic is therefore a basic requirement for adequate public health preparedness. In this study the extended parallel process model (EPPM) is applied to investigate how the readiness of municipal employees to report to work during an influenza pandemic (IP) is affected by individual attitudes and environmental conditions. METHODS: 1.566 employees of a major German city participated in a cross-sectional online survey. The questions of the survey covered the dimensions of risk perception, role competence, self-efficacy, role importance, sense of duty, and willingness to report to work in the case of an IP. Data were analysed by means of path analyses. RESULTS: Data suggest that up to 20% of the public service workers were not willing to come to work during an IP. Willingness to report to work was increased by the perception of a high working role competence, a high assessment of role importance, high self-efficacy expectations, and a high sense of duty. Negative effects on willingness to report to work were identified as the perception of a high risk to become infected at work and the perceived risk to infect family members. The decomposition of direct and indirect effects provided important insights into the interrelationships between model variables. CONCLUSIONS: Measures to increase municipal workers' willingness to report to work in case of an infectious pandemic should include communication strategies to inform employees clearly about their particular tasks during such critical events and training exercises to increase their confidence in their competences and skills to fulfil these tasks.