The Steps from EbM to CLINECS (Clinical Economics)

Both "rare diseases" and "pandemics" are cooked with the same flame and are exposed to the same burn risk: The problem relies on the business model of driving demand for diagnostic and treatment strategies by stoking fear of deadly consequences. This problem affects citizens and policymakers because action is already being urged to prevent the next pandemic.

This strategy can induce permanent stress that can be applied to all other nameable health problems, e.g., rare diseases, and builds artificial pressure that undermines the careful development of prevention strategies. With the proclamation of the pandemic, science in Germany was "muzzled," and the social, mental, and physical health of the population and the economy of the country were more severely affected by the proclamation of the Covid 19 pandemic than in the last 70 years.

No one doubts the existence of Covid 19 disease. However, evidence of a pandemic has never been provided in Germany. The criterion of excess mortality of a pandemic can now only be found in textbooks, but no longer on the Internet.

With the support of the Federal Statistical Office, we were able to present data confirming that there was no excess mortality in Germany prior to the proclamation of the pandemic and to confirm, using Brazilian (due to the lack of German) data, that there was no correlation between a positive PCR result and hospitalization: Porzsolt F, Kroemer R, Silva-Sobrinho RA. The two sides of the value coin - confirmed or not by Real-Word Effectiveness? VBHC Thinker Magazine Christmas Issue Dec. 2022: 40-43. The theory on the induction of fear by the communication of bad news is described in Porzsolt F, Pfuhl G, Kaplan RM, Eisemann M. Covid-19 pandemic lessons: uncritical communication of test results may do more harm than good and raises questions about standardized quality criteria for communication and liability. Health Psychology and Behavioral Medicine 2021;9:818-829. DOI 10.1080/21642850.2021.1979407. This communication effect has paralyzed science and weakened the German economy.

We need to solve the following problems: 

1. two-dimensional diagnostic tests (e.g., radiographic mammography with histopathologic reference) can confirm an existing disease but not a uni-dimensional measure (e.g., body temperature or polymerase chain reaction; PCR).

A test in the hands of a clinically inexperienced therapist is more dangerous than a scalpel in the hands of an inexperienced surgeon. The surgeon is alerted to the error by his team and an injecting artery, whereas the misuse of a test is difficult to detect without careful analysis of the clinical problem, the current state of information, and the accompanying risk factors.

2. In a world of experimental studies (to confirm proof of principle; PoP), only statistical thresholds are essential. In the chaotic conditions of everyday care (confirming Real-World Effectiveness; RWE), the risk of overtreatment cannot be prevented without defining clinical thresholds. Two important conditions need to be confirmed by clinical thresholds: a health condition that requires treatment and a treatment strategy that has been shown to reduce the existing health problem.

The squaring of the circle for rare disease management involves the reduction of affected families and the environment. For this purpose, 10 aspects need to be defined:

1) Forms and functions of squaring the circle (circle-square).

The function of the circle-square is to offer health services under the non-structured conditions of "natural chaos" in everyday care, but also well-structured conditions in order to measure unbiased results replacing randomization with Bayes' principle. Patients are followed up by the treating physician in a step-by-step linkage with the "rare disease" expert. Standardized selection of endpoints and standardized "endpoint-specific risk classification" of each patient allows comparison of outcomes for each measured endpoint among risk-matched patients treated with precisely described but completely different strategies. 

2) Selection of recruitment regions.

Depending on the target disease, define the target region (county, state, continent)-.

3) Definition of efficient standardized diagnostics.

The algorithm of the obligatory diagnostic spectrum needs to be defined. Feasibility must be ensured for each individual patient.

4) Announcement of the project in the recruiting region with a contact center.

In the selected region, the concrete, and centrally managed care offer needs to be communicated via a central contact center.

5) Implementation of regional coordinators.

The central project management may only succeed if each regional health coordinator has sufficient time, is sufficiently mobile, and is sufficiently networked through telecommunications to keep the patients, their families, the supervising local physician, the regional hospital, and all cooperating partners to date on the project at all times.

6) Recruitment Steps.

The uniformly conducted telemedicine recruitment should be structured through central project management to perform the essential information steps in the required sequence and to transmit them to all partners involved.

7) Monitoring (safety, implementation, and outcomes data).

For data collection to ensure sponsor and project safety, monitoring should follow the same control principle as recruitment.    

8) Care Strategy.

The care strategy must be created according to the preventive service (primary, secondary, or tertiary), taking into account the "threshold quartet". The threshold quartet consists of two pairs of thresholds, each of which, through a clinically defined assumption and its statistical confirmation (or rejection), confirms respectively a) an existing condition requiring treatment and b) an available method by which the reduction of the existing health problem has been confirmed.

9) Confirmation Check.

In collaborative projects trust is noble, but confirmation is effective. A confirmation check is almost always possible and saves a lot of trouble when working with colleagues.

10) Team closing party with awarding of certificates (to all involved, patients, family/helpers, health personnel, involved companies, and sponsors).

We consider the tenth regulation significant to send two emotionally significant signals to society. Those affected should express the perceived value and gratitude they have experienced. The helpers should make society aware of the considerable difference between the ideal value that each helper feels through the help provided and the commercial remuneration that can be paid for the service provided.

The solution our team can offer concerns basic problems of a) any care under unstructured conditions or b) any experimental research or c) any health services research under well-structured but non-experimental conditions on patients with any form of rare (or undetected form of a frequent) disease.

If "only" care without systematic data analysis is envisaged, we propose to organize a "mega-party to optimize health care in the region" involving all stakeholders (see above) to motivate and convince the active and passive participants in the action of the added value that can be achieved by care WITH structured data collection compared to care WITHOUT structured data collection.

If an experimental research project is to be conducted to demonstrate proof of principle, an RCT (Randomized Controlled Trial) needs to be conducted.

If a non-experimental, pragmatic (unbiased) comparison of different care options is to be conducted, a PCT (Pragmatic Controlled Trial) should be considered.

Special programs can be offered to train the necessary (local) staff to conduct these projects locally or, if interested, to work in other regions as highly qualified "healthcare data managers (HDMs)". 

Those who have learned to document a rare disease can also document any common disease.

We recommend that everyone who needs care receive it. However, we are also concerned about the potential overuse of care and the inevitable strain on the system's human resources. Therefore, we strongly recommend implementing the "clinical economics" mindset, which focuses on balancing "costs and consequences" and on the benefits to patients or other members of the system. If the benefit of health care to any of these members is greater than the benefit to the patient ... then we should ask ourselves if we are still on the right track. The additional questions asked - to my mind - may not fit the situation in which a physician encounters a patient after an odyssey through the system.

The Institute of Clinical Economics is represented by seven teams. A large part of the expertise required to solve the tasks at hand is available there.

Board of Directors Franz Porzsolt MD, PhD1,2, Tobias Weirauch MD1,2, Christel Weiss PhD1,3 , Monika Karstens Office Management & Treasurer1, Manfred Weiss  MD, PhD1, 4

Six Health Services Research (HSR) Departments

HSR – Developmental Sciences   Franz Porzsolt1,2, Christel Weiss1,8,  Manfred Weiss1, 4, Philipp Legrum1,9, G.Oscar Kamga Wambo MD1,2,6,7, Susanne Becker MD, MPH, MSc Health Economics and Policy, MA Public Policy1,5, Florian Lautenschlager MD1,4,5

HSR – Applied Sciences      Horst Kunhardt PhD9,10, Reinaldo A. Silva-Sobrinho PhD1,7, Franz Porzsolt MD PhD 1,2

HSR – Tracing Scientific Evidence Barbara Herzberger MD1,3,5 Rupert Krömer8,9, Robert Gerl MD1,8,9  

HSR – Language Edition Service

Barbara Herzberger MD 1,3,5

HSR – Personnel Management, Mobility and Business Administration Manfred Weiss1, 4, Bettina Hailer Dr.11, Silvia Frankenhauser12

Legend:          

1 Clinical Economics

2 Internal Medicine

3 Surgery

4 Anesthesiology / Intensive Care

5 Psychology / Psychiatry

6 Public Health

7 Infectious Disease / Epidemiology

8 Biomathematics, Statistics, Information Processing

9 Computer Science

10 University Management

11 Business Administration

12 THE - Travel Hospitality Experts

Our team emerged from what was then the largest department of hematology/oncology in Germany. The care of acute leukemias was the core task of the department. Considering that every general practitioner will see only a single patient with Acute Leukemia in the course of his or her professional career, one can imagine that this disease brings with it all the problems (including those of acute risk) that make a rare disease an emergency case. We were familiar with the problem of "Friday leukemia," which was regularly referred to us from surrounding hospitals around 4:00 pm on Friday because, in the smaller hospitals, the risk was too high to keep a patient in their own hospital (with reduced staffing) over the weekend without a clear diagnosis and care strategy. 

Even in a maximum-care hospital, the assignment of a patient with a life-threatening illness requires the maximum commitment of all colleagues involved in all departments.    

Only in larger hospitals the teams and the cooperating departments will be perfectly coordinated so that the entire diagnostic process, including initial treatment, can be completed in four hours and the background service over the weekend can be provided with all the necessary information within this time.

Not every rare disease needs to be treated under this time pressure but appears with other concerns to the physician, who can bring about the hoped-for clarification through the preliminary work of the colleagues.

The biggest hurdle to our project idea is the resistance of almost all stakeholders to a switch from performance-based to value-based financing of healthcare services. The most likely cause of this resistance is fear. Producers of products and providers of services may fear, that some of the users of an offering do not value it as highly as the providers do and therefore fear a reduction in revenue. 

Only providers who are absolutely convinced that no losses will result from the switch to value-based assessment will not worry. For this reason, we have already started thinking with actuaries about reducing the risk of loss for providers of products and services in a transition phase by offering a "risk balancing strategy" free of charge. This would increase the chance of project feasibility. 
Skimming profits to fund unexpected losses could mitigate hard-to-predict risks in the early years after the funding transition. If the expected psychological effect of this "risk-balancing strategy" (the reduction of fear of an existential threat) can be achieved, the chance of implementing the project will increase.

Our team is applying for this project because (a) we see no other way to balance the affordability of health care with its measurable value, and (b) the concept of a "risk-balancing strategy" will be easier to implement in the context of a small, scientifically controlled project than in a large-scale project

To this end, I should explain that I had taken on various roles as a team lead. Based on this practical experience, the conviction developed that there is a significant difference between the mindset of a practitioner caring for patients or a politician making decisions and the completely different mindset of scientists who have to critically question the statements of their colleagues and their own statements. In other words, practitioners and politicians must trust the statements they work with. Scientists must not trust the statements they work with, they must critically question these statements. See J A Muir Gray. Evidence-based policy making. BMJ  2004; 329:988-9 (Scientists make decisions policy makers take decisions). Here's a practical example:

I received my medical training and advanced training in hematology/oncology traditionally at a medical school and in clinics. In parallel, I developed a measurement method (which was also patented) in laboratories of the pharmaceutical industry during my medical studies and was subsequently able to learn immunological methods at the Ontario Cancer Institute in Toronto with a grant from the German Research Foundation (DFG). Since then, I have been scientifically active throughout my clinical career and have published > 500 publications to date (2/3 as first author). 
I immediately ended this dual role as a clinical practitioner and as a scientist when one of my cancer patients asked me in consultation, "Doctor, do you yourself trust the therapy you just recommended to me?" I was shocked by this question because I had interpreted it as evidence that patients can very well perceive whether a doctor trusts the recommendation that he offers to his patients. On that day, I decided to work only as a scientist, but no longer as a clinician.
From these experiences, the conviction has developed that clinical experience is a "sine qua non" for conducting "experimental clinical research" and "pragmatic health services research." However, a clinically responsible activity cannot be combined with a scientifically responsible activity at the same time, because the two tasks do not infrequently require competing trade-offs (regarding the distribution of the dimensions of space, time, money, and trust). This requires two "heads" just as in the game of chess, where it is also hardly imaginable that two different strategies can be developed against each other in one "head". 
My connection to the community of my patients was shaped by my socialization. I grew up as the son of a general practitioner (whose practice I was supposed to take over, but to my father's greatest disappointment did not), two of my siblings, my wife, and her siblings are professionally involved in the care of patients. Since my scientific understanding of medicine has defined the quantity and quality of patients' lives as the primary endpoints of care, my interest was paved very early - but unconsciously - in the development of "Health Services Research". The attempt to combine care and research in practical life has fortunately failed because one task per person is enough to fill a lifetime with it.

"Clinical Economics (CLINECS)" contributes to innovations and sustainability in three ways:

(A) Development and application of tools

(1) Diagnostic test or measurement

In the field of diagnostics, the difference between "one-dimensional measurement" and "two-dimensional test" should be described by their exact functions and forms (structures). Concrete proposals and examples have been developed, but still need fine-tuning and publication. Without clear differentiation, the measurements and tests will be confused and lead to avoidable errors and their consequences.  

(2) Polymerase Chain Reaction Form and Function.

The description of the form and function of the polymerase chain reaction (PCR) in the 1987 Original US Patent No. 4683195 does not completely match the descriptions of the methodology and its significance in 30 international textbooks examined to date, some with the same wording. These minor discrepancies should be corrected as potential sources of misinterpretation.

In order to establish a consensus with publishers and scientists, we (a computer scientist from our association together with colleagues from different disciplines) have drafted the concept of a project whose realization requires costs of about € 1 million. Our efforts to raise this sum have so far failed solely due to the lack of priority accorded to this project.

(3) Proof of the need for action (conflict of terminology)

(4) Development of the tool for assessment of Real-World Effectiveness (RWE) The experimental results of randomized trials are used as a basis for clinical, ethical, and legal decisions. We were able to optimize the strategy for detecting RWE by the idea of offering the supply under the unstructured conditions of "natural chaos" but performing the evaluation under structured conditions. This "squaring of the circle" was achieved by replacing experimental randomization with the non-experimental (pragmatic) Bayes' principle. Each therapist can coordinate his care strategy with his patient. For this purpose, the measured endpoints had to be defined in advance and the individual risk profile of each subject (high/intermediate/low) with respect to each measured endpoint had to be determined according to a uniform classification. This strategy of "endpoint-specific risk classification" is the core of each Pragmatic Control Trial (PCT). However, it greatly facilitates care and evaluation because the endpoints and time points of evaluation are based on clinical indicators, and reminders are sent by the IT system. Stratification of patients at the individual endpoint-specific baseline risk allows the outcome for each endpoint to be determined as a function of the subject's individual baseline risk. In addition, the test groups and control groups can each be oriented based on the study guideline group questions if the limitations of multiple testing are taken into account, e.g., by Bonferroni corrections.

Further contributions are mentioned only by title due to limited space.

(5) Development of the three-dimensional strategy.

(6) Difference between expected and observed outcomes.

(7) Lack of internal consistency between the building blocks of clinical trials.

(8) The threshold quartet.

(9) The importance of inclusion and exclusion criteria.

(B) The keystone between care and research (see A4).

(C) The cube of care conditions (CCC).

A sensible approach, as I see it, would be a multi-professional structure of a new specialty "Clinical Economics", which should be taught in varying degrees of differentiation in all professional fields of healthcare. Based on the work that is already done, this structure can be prepared in one year and completed in another year, if the financial resources are available and the interested authors are known to contribute from the perspectives of the

1) Core areas of the problem (medicine, psychology, economics)
2) Generally applicable rules (mathematics, computer science, philosophy) 
3) Culture-dependent norms (law, ethics, political science)

These areas need to be aligned with public health goals.

In the first year, I would set up an office in Ulm (to avoid the physical and time burden of traveling) to structure the project, and in the second year, I would fully implement the project. Templates are the three books on "Clinical Economics":

F. Porzsolt, A.R. Williams, R.M. Kaplan. Clinical economics. Effectiveness and efficiency of health care management. 2003 Ecomed Verlagsgesllschaft AG & Co KG, Landsberg / Lech, Germany.

Franz Porzsolt, Robert . Kaplan. Optimizing Health - Improving the Value of Healthcare Delivery. 2006 Springer Science and Business Media

Franz Porzsolt. Fundamentals of Clinical Economics. 2011. self-published by the PVS Association, Berlin, Germany.

A "Quadriga of Clinical Trials" (with the introductory publication) is ready for submission to publication.

My goal 45 years ago was the description of effects of healthcare interventions that predict with sufficient reliability the outcomes in patients (with a known risk profile). We have been able to offer this method since we understood that measures of care must be offered under the non-structured conditions of "natural care chaos" but can only be measured under structured but non-experimental conditions. This squaring of the circle had to be resolved, and we succeeded in doing so by replacing the experimental method of the Randomized Controlled Trial with the non-experimental Bayes' Principle. The task now is to implement this fully developed strategy in everyday care.

Various reservations stand in the way of this implementation. The abandonment of randomization is rejected by some colleagues as an unscientific strategy. Others fear having to accept unpredictable changes in values, and a third group fears ending up in a chaotic care dilemma. With objective indications, however, the unpredictable and unavoidable chaos can certainly be averted. A structured derivation of easily interpreted data can be derived. This new form of evaluation of health care services makes it possible to change from a performance-oriented to an outcome-oriented evaluation and financing.

The number of invitations received daily to submit a manuscript in exchange for the payment of a "small" APC is literally exploding. Two journal publishers have invited me to edit a special thematic volume. Without support for the development of the necessary infrastructure, these offers are probably more visionary than missionary.

Our solution has sunny and dark sides. The desired financial relief for affected families can be ensured by a general reduction in spending on healthcare lines. The dark side consists of the fear of the manufacturers of products and the providers of services sliding into an economically threatening situation of the change from performance-oriented to outcome-oriented financing. On the one hand, this fear is not unfounded, because we assume from 40 years of clinical experience that about 50% of all products or services offered can be replaced by less expensive but equally effective offerings. On the other hand, the possible demonstration of everyday suitability up to approval can save significantly more than 50% of development costs and development time. Since the differences in costs for both sides, users and manufacturers/service providers will be considerably greater than the differences in achievable outcomes, there remains room for optimization for both sides.       

The burden on families and the carbon footprint can only be reduced for patients with unexplained diseases by avoiding an odyssey. To this end, a reminder algorithm for primary care physicians that suggests the optimal sequence of primary diagnostic measures based on leading symptoms is valuable. If the diagnosis remains unclear, a rare disease center should perform a narrowing of the remaining spectrum of known rare diseases as a secondary diagnostic measure. Consensus decisions by this center could recommend tertiary diagnostic measures to clarify the remaining rare diseases.

Four aspects had to be taken into account for this:

1. the recommendation of Albert Einstein: "A problem cannot be solved by the way of thinking that caused the problem".
2. the recommendation of American architects and designers: "2form Follows Function".
3. to take up the claim formulated by the founders of the "ulmer hochschule für gestaltung (Ulm Academy of Design)" after the Second World War to develop not only individual but universally valid solutions with social relevance.
4. to survive academically without public funding for several decades through the support of moved colleagues and students.  

There are three reasons why the new solution is likely to be successful:

1. the solution follows the two recommendations of Albert Einstein: "A problem cannot be solved with the mindset that caused it" and the designer's recommendation: "Form Follows Function".
2. we have been working on the solution for 45 years and have made continuous progress without indication of a dead end in the solution path.
3. 14 of 114 references guiding the way to the solution are attached.

• Porzsolt F, Rocha NG, Toledo-Arruda AC, Thomaz TG, Moraes C, Bessa-Guerra TR, Leão M, Migowski A, Araujo de Silva AR, Weiss C. Efficacy and Effectiveness Trials Have Different Goals, Use Different Tools, and Generate Different Messages. Pragmatic and Observational Research 2015;6:47-54. DOI http://dx.doi.org.ezproxyberklee.flo.org/10.2147/POR.S89946
• Porzsolt F. Clinical Economics and Nursing. Rev. Latino-Am. Enfermagem  2015;23: On-line version ISSN 1518-8345. http://dx.doi.org.ezproxyberklee.flo.org/10.1590/0104-1169.0000.2640
• Porzsolt F, Jauch KW. Real-World Usefulness Is Missing. Dtsch Arztebl Int. 2018;115:114-115. doi: 10.3238/arztebl.2018.0114c.
• Porzsolt F. The assessments of three different dimensions “Efficacy”, “Effectiveness”, and “Value” require three different tools: the Randomized Controlled Trial (RCT), the Pragmatic Controlled Trial (PCT), and the Complete Economic or Cost-Effectiveness Analysis (CEA). Surg Rehabil, 2018;2(4):1. doi: 10.15761/SRJ.1000145
• Porzsolt F, Wiedemann F, Becker SI, Rhoads CJ. Inclusion and exclusion criteria and the problem of describing homogeneity of study populations in clinical trials. BMJ Evidence-Based Medicine 2019; doi:10.1136/bmjebm-2018-111115
• Porzsolt F, Becker SI. Rapid response to: Moustgaard et al. Impact of blinding on estimated treatment effects in randomized clinical trials: meta-epidemiological study. BMJ. 2020;368:l6802. doi:10.1136/bmj.l6802. Rapid response.
• Schmaling K, Kaplan RM, Porzsolt F. Efficacy and effectiveness studies of depression are not well-differentiated in the literature: a systematic review. BMJ Evid Based Med. 2020 Mar 18. pii: bmjebm-2020-111337. doi:10.1136/bmjebm-2020-111337.
• Porzsolt F, Jauch K-W, Kaplan RM. 100 Years BAUHAUS Dessau/Germany: What designers of clinical studies can learn from designers and architects of BAUHAUS Dessau and hochschule für gestaltung ulm/Germany. Int. J. Surgical Procedures 2020;3.1:1-7 DOI:  10.31021/ijsp.20203133
• Porzsolt F, Matosevic R, Kaplan RM. Recommendations for cancer screening would be different if we measured endpoints that are valid, reliable, specific, and important to patients. Cancer Causes & Control 2020; https://doi-org.ezproxyberklee.flo.org/10.1007/s10552...
• Porzsolt F, Weiss Ch, Weiss M, Jauch K-W, Kaplan RM. Demystification – a Solution for Assessment of Real World Effectiveness?  Trends Med 2020;20:1-2 doi: 10.15761/TiM.1000231
• Porzsolt F, Wiedemann F, Phlippen M, Weiss C, Weiss M, Schmaling K, Kaplan RM. The terminology conflict on efficacy and effectiveness in healthcare. J Comp Eff Res. 2020;9:1171-1178. doi: 10.2217/cer-2020-0149.
• Wiedemann F, Porzsolt F. Measuring Health-Related Quality of Life in Randomised Controlled Trials: Expected and Reported Results Do Not Match. Pragmat. Obs. Res. 2022 Apr. 11;13:9-16. Doi 10.2147/POR.S350165. PMID: 35431592; PMCID9012498.
• Porzsolt F, Weiss Ch, Weiss M. Covid-19: Twin Methode zum Nachweis der Real-World Effectiveness unter Alltagsbedingungen [Covid-19: Twin method for demonstration of real-world effectiveness (RWE) under the conditions of day-to-day care]. Das Gesundheitswesen 2022;84:1-4. DOI: 10.1055/a-1819-6237 ISSN 0941-3790
• Porzsolt F. Kroemer R, Silva-Sobrinho RA. The two sides of the value medal – confirmed or not confirmed by Real-Word Effectiveness? VBHC Thinker Magazine Christmas Edition Dec. 2022: 40-43.

Four members of our 20-person voluntary team provide regular contributions. All members work on a voluntary basis. One member receives a lump sum for taking over two functions of the association. 
With the topics we have worked on in the last 20 years, we have only been able to raise small amounts of donations but no funding. 
Our list of publications justifies the hypothesis that the volume of financial support for science may be less important than suspected. It is certainly an attractive task to find out which kind of funding the scientific output is most efficient.  

About 45 years ago, we began to recognize the existing problem. However, we found the solution to the problem only a decade later: The significant difference between the results of care in the international literature and the results we observed in our own patients confirms the difference between the described EFFICACY and the observed EFFECTIVENESS. 

The focused work started about 20 years ago. In the period between the years 2000 and 2023, we published 114 papers related to this topic 14 of these references are included in our application.

A QUADRIGA of clinical trials (+ introduction) is ready for publication.

Diversity, equity, and inclusion are - according to my perception - natural laws of intercultural coexistence. In my private and professional life, I have experienced these challenges many examples but felt an unsolvable problem only when the rules of my own society stood in the way of solving the challenge.

First of all, I would like to express my appreciation to the MIT team for the excellent set of questions.  Please consider - if you have not already done so - making this catalog available to all social institutions in all countries for the eradication of unsuccessfulness and poverty. The business model question was not relevant to me as a scientist until I understood that the antiquarian - but no other value - of the best scientific solution without a business model in my desk drawer will increase daily.
The ideal value of our solution is a shift from performance-based to value-based healthcare financing. However, this value is perceived differently by different groups in society.
The business model can only be successful if it combines the "ideal value" with a "business value" that has a very high priority from the perspective of the decision-makers.

The added value we generate, Real-World Effectiveness (RWE), will create undesirable effects on the business models of various partners by eliminating services with lower RWE. If it is not possible to compensate for these undesired effects completely with a successful business model, the necessary interest will hardly be aroused among the decision-makers to jointly implement the combination of an ideal and a business value. 
The combination between the ideal and business value will succeed if we, the society - represented by our politicians - confirm that the three-dimensional structure for evaluating health leads can reduce the development costs and the development period for proving suitability for everyday use and the associated approval by 70% - 80%.
This reduction is plausible because the number of Randomized Controlled Trials (RCTs), which are very time-consuming and costly to conduct, can be reduced to an absolute minimum. Two or three methodologically sound RCTs will be sufficient to demonstrate proof of principle (PoP) in all (!) countries. This will save a considerable part of the development costs. Once the PoP is proven, the proof of RWE can begin. This proof has two objectives. the supply contract is combined with a research contract. The goal of the utility mandate is met if a health problem requiring treatment can be solved at an acceptable cost and burden to the affected individuals and society. The objective of the research mandate is to demonstrate the achievement of goals prospectively defined by the respective affected individuals and society. It is plausible that the costs of fulfilling the joint care and research mission will also be borne jointly by the parties who are beneficiaries of this ideal and economic model of success.

My parents advised me to devote my available time and energy to the pursuit of goals that I feel the greatest inclination and ability to solve. Therefore, I devote myself with pleasure to my scientific tasks and prefer to spend a day in unsuccessful deliberations to solve a scientific problem than in an unsuccessful search for financial support. 

Successfully acquiring research funding is as much about talent and expertise as any other successful activity. My resources are too limited to successfully fight on multiple fronts at the same time. 

Potentially, MIT could offer its strategy of identifying innovative projects and funding their promotion to many societies that are unable to discover their own innovation potential. Societies should use this strategy to identify favorites themselves while using MIT's evaluation criteria and communicating their findings with MIT for further development of a global funding structure. 

My applications for research funding were successful at the beginning of my scientific career. In 1974, I received a research grant from the German Research Foundation (DFG) to work for 18 months at the Ontario Cancer Institute in Toronto/ONT. There I learned to apply strategies for critical analysis of scientific concepts. After returning to Germany, I applied this critical analysis strategy but had to quickly realize that this strategy was perceived as "self-defeating" and "nest-beating" and the sources of funding for my submitted projects quickly dried up.

For me, there were two options to choose between: Either to continue on the path I had chosen or to stop doing scientific work. I could not imagine changing my own convictions, although I was aware of the risk, I was taking by ruling out a third option. The awarding of the German IQ Prize in 2013 by the German section of MENSA International (https://idw-online.de/de/news529824) was a moving signal for me.