Background
Challenges of “standardisation” and “individualisation” have always been characteristic
for medical services. In terms of individualisation, the best possible individual
care is the ethical imperative of medicine, and it is a good right of any patient
to receive it. However, in terms of standardisation, all the available treatments
are based on guideline recommendations derived from large multicentre trials with
many thousands of patients involved. In the most optimal way, the standardisation
and individualisation should go hand-in-hand, in order to identify the right patient
treating him/her with the right medication and the right dose at the right time point!
Further, in paradigm and anticipation, there is a big discrepancy between “disease
care” and “health care” which dramatically impacts ethical and economical aspects
of medical services.
Several approaches have been suggested in ancient and modern medicine to conduct medical
services in a possibly optimal way. What is the difference amongst all of them and
how big is the potential beyond corresponding approach to satisfy the needs of the
individual, the patient, professional groups involved and society at large?
On behalf of the “European Association for Predictive, Preventive and Personalised
Medicine,” the dedicated EPMA working group provides a deep analysis in the issue
followed by the expert recommendations considering the multifaceted aspects of both
“disease care” and “health care” practices including ethics and economy, life quality
of individuals and patients, interests of professional groups involved, benefits of
subpopulations, health care system(s) and society as a whole.
Traditional, complementary and alternative medicine (TCAM)
TCAM, also called “integrative medicine,” is considered as an amorphous concept comprising
a range of ancient, long-standing but still evolving treatment approaches being practised
mainly in their countries of origin as well as in countries into which corresponding
expertise has been “imported” [1]. TCAM refers to health practices, approaches, knowledge
and beliefs incorporating plant-, animal- and mineral-based medicines, spiritual therapies,
manual techniques and exercise (e.g. in form of acupuncture, dietary therapy, herbal
medicine, moxibuston, TaiJi, Ayurveda, amongst others) applied singularly or in combination
to diagnose, treat and prevent illnesses or maintain well-being [2]. However, the
educational level of the doctor is critical for the quality of TCAM that depends on
the national/local curricula varying substantially from country to country and, therefore,
may not be adequate enough to fully realise potential benefits of various forms of
TCAM modalities. TCAM approaches are frequently considered as being non-evidence based
[3]. Further deficiencies arise from evident philosophical and religious differences
as well as some cultural barriers between the countries of origin and countries into
which TCAM is “imported” [1]. Nevertheless, in addition to the conventional medicine,
TCAM is getting more and more popular and well-pursued in Western countries. From
view point of predictive and preventive medicine, TCAM provides a unique expertise
for recognising the so-called suboptimal health conditions before a clinical manifestation
of severe pathologies [3–5]. These global trends make particularly attractive consideration
regarding innovative hybrid approaches which would utilise advantages of both TCAM
and modern medicine and, therefore, benefiting patients and enriching the spectrum
of tools and overall expertise of the dedicated professional groups assuring the reproducibility
of TCAM technologies and outcomes [6]. However, those approaches are currently underdeveloped
and require additional major efforts in terms of multi-professional collaboration,
scientific and technological discoveries and extensive financial support.
Person-centred medicine
The main idea of the person-centred medicine is to promote health and, therefore,
reduce disease burden. In this concept, any health condition is considered as an individual
state of physical, mental, social and spiritual well-being. Contextually, health care
approaches are prioritised by person-centred medicine compared to a disease care.
Humanistic interpretation of medicine is characteristic including the articulation
of science, enhanced understanding of positive health versus illness, emphasised personalisation
of all medical services as well as strong patient empowerment and essential responsibility
of every person, at individual and community levels. “All for one and one for all”—a
smart but perhaps a bit naive slogan introduced by the Three Musketeers fits well
to the philosophy of the person-centred medicine. Therefore, a realisation of those
ideas demands clear definitions and validated strategies to reach a reasonable level
of maturity in health care [7].
Individualised medicine
A great strength of individualised medicine (IM) is to provide a holistic and integrative
approach for medical care. IM comprises curative, rehabilitative and preventive examination
as well as treatment methods customised for the individual and the patient [8]. IM
well recognises a multidimensional interaction of internal and external risk factors,
genetic background, age, gender, environmental risk factors, lifestyle, culture and
beliefs as well as social status in the overall predisposition of individuals to specific
diseases, the disease development, the natural course of disease and the response
to therapeutic intervention. These factors vary from individual to individual. Contextually,
IM aims to categorise patients into clinically relevant subgroups (that is the content
of the “Stratified medicine” —see below). Hence, at the heart of the concept of IM
is a stratification that “individualises” a one-size-fits-all standardised intervention
into a group-specific intervention. Less clear concepts and approaches are provided
by IM towards “predictive and preventive medicine”—see below.
Stratified medicine
Stratified medicine means looking at large groups of affected individuals (e.g. cancer
patients) to try and find ways of predicting which treatments/patient sub-types are
likely to respond to. Specifically in cancer, it involves looking in detail at the
cancer cells and their genetic make-up. The purpose of the approach is to find out
which treatment algorithms are more likely to work [9]. Patient stratification is
one step towards individualised patient treatments and so-called “personalised medicine”—see
below.
Personalised medicine
The term “personalised medicine” is the keyword to refer to the best possible, most
optimal and innovative medical approaches in the early twenty-first century, to justify
grant applications and to receive dedicated budgets. However, in order to make anticipation
by personalised medicine as realistic as possible, this term should be pragmatically
sub-divided into its clear subcategories, namely “semi-personalised” versus “true
personalised” as it has been discussed and published elsewhere in scientific literature
[10].
“Semi-personalised medicine” compromises between standardisation and individualisation
in medicine, the first step of which is the stratification of big patient-groups according
to certain well-known characteristics (e.g. specific biological characteristics of
the tumour). In the next step, individual patients within the group are treated according
to the algorithms adapted to the entire stratified group. Consequently, the treatment
efficacy varies from patient to patient within the group, since a limited number of
characteristics in common is considered by the treatment algorithm; all other individual
characteristics are not taken into account but may sufficiently impact individual
outcomes.
“True personalised medicine” is based on the “individual patient profile” (see “Predictive,
preventive and personalised medicine (PPPM)” section) directing to a tailored therapy
that maximises the efficacy for that one patient in particular.
However, a disadvantage of “personalised medicine” is that its contents are adapted
to the needs of disease care for treatments of diseased individuals and individual
patient cohorts but not for health care of individuals to maintain in a good mental
and physical shape avoiding clinical manifestation of diseases.
Precision medicine
The terms precision, personalised and individualised medicines are often used interchangeably
[11]. Precision medicine is a concept of therapeutic and preventive modality for disease
that takes into account individual variability in genes, environment and lifestyle.
It refers to the tailoring of medical treatment to the individual characteristics
of each patient [12]. Precision medicine is considered a relatively new approach in
disease and health care, although it has been around for a while and has limited application
in certain fields of medicine such as blood transfusion and organ transplantation.
Further, precision medicine faces a number of serious challenges that need to be addressed
[13–18] as summarised below.
Knowledge gap: Extensive and costly long-term education is required for all health
care system authorities, physicians and participants to fully understand the dynamic
and potential objectives of precision medicine.
Authority and interpretation: Even for the field specialists, an interpretation of
DNA data for individual health outcomes remains sophisticated and the problem of interpretability
continues to grow. Consequently, many doctors are simply not able to make sense of
genetic tests and to communicate the results accurately to their patients.
Data storage: Gene sequencing of an individual produces massive amounts of data. The
sequencing of thousands, if not millions, of people will produce unimaginable amount
of data. How will we store the data and effectively analyse to derive useful information
and to interpret the data?
Pathogenic mechanism: Many diseases have complex and multifactorial pathogenic mechanisms
which would make it very difficult to identify a specific gene responsible for their
manifestations.
Most technologies and equipment required for effective implementation of precision
medicine are still in embryonic stages.
Privacy/security: Cyberattack is increasingly a major hurdle to maintaining privacy
and security for all particularly given the current state of world affairs. Such valid
concerns are already well-recognised for economic, energy and defence sectors across
the globe. Precision medicine relies on massive public and personal data requiring
sophisticated and extensive infrastructure and technology. Thus, vulnerability due
to breach of security and privacy violation could have devastating consequences for
the successful implementation of precision medicine [19] and data misusing, e.g. for
economic and political purposes with a consequent discrimination of affected individuals
and even (sub)populations involved in the database containing sensitive genetic information
and family history amongst others.
Coordination and policies: For precision medicine to have its greatest impact, federal
and private health insurance companies have no option but to become comfortable with
value-based drug pricing.
Variability of phenotypic features in population: It is difficult, if not impossible,
to detect, decipher and utilise phenotypic characteristics of every individual as
indicators for diseases as seems to be proposed by precision medicine.
Data relevance: The usefulness of data gathered from smaller groups may not be sufficient
to make larger population health recommendations.
Culture: Prevention of abuse of information for unintended purposes such as screening
potential partners and denying insurance coverage is a serious concern. How will this
affect the culture? Will we be cultivating a different kind of racism, on a genetic
basis?
Ownership: Who will have ownership of the data? Will it be the government? It is noteworthy
that the FDA has blocked companies from allowing individuals to have access to their
own genetic information. Will this change as part of the new initiative?
Compliance: There is no binding protocol to guarantee that all individuals would follow
the recommendations made by precision medicine so the diseases could be prevented,
controlled or cured.
Drug/device industry: Genetic research and development of treatment options have been
very promising and productive in the private sector. How will government involvement
affect research? Will governmental agencies work cooperatively with them or competitively?
Diversion from overarching goals of health care system: The focus and concentration
of human and financial resources on precision medicine may divert attention and concerns
of health care system from efforts to remedy the foundational causes of ill health
such as poverty, obesity and education.
Health care costs: Genetic mapping of a population, and analyses of data, securing
the information and deriving treatment recommendation are very costly which can be
readily hampered by budgetary constraints of high dynamic economies. Further, the
costs of converting the intellectual capital to therapeutic modalities must also be
taken into account and built into the health care system.
Finally, it is noteworthy that the concept of precision medicine may be a repackaging
of the ideals advanced by the human genome project in 2000. The hope was to identify
genetic markers for the ultimate objective of developing novel biomarkers and overcome
perceived therapeutic deficiencies and overcome the pressing issue of non-responders.
However, this noble objective has not been fully materialised yet, leading one to
the question: Is precision medicine “old vine in a new bottle”?
In conclusion, precision medicine could potentially improve preventive methods and
therapeutic options. However, a number of challenges remain as alluded to above—see
also the cartoon in Fig. 1. Precision medicine will have to demonstrate consistency,
coherence, comprehensiveness, clarity and relevance to every individual and community
impacted by these developments in medical research and treatment. Will precision medicine
deliver all that it promises? With increasing shrinking of financial resources, is
it wise to invest millions of dollars/euros in an approach for which its risks versus
benefits ratio does not ring a satisfactory bell? Perhaps, stakeholders and authorities
would be better off to further invest and focus on the already established concepts
of “predictive, preventive and personalised medicine.”
Fig. 1
“Precision” itself does not guarantee for better understanding of an issue. An old
wise dictum adopted by all European cultures/languages warns—one cannot see the forest
for the trees. Hence, technologically driven higher resolution of individual elements
does not automatically mean that you can better recognise the complex problem which
you are looking for, particularly when the zoomed element (the tree) is prioritised
and/or pulled out from the overall context or zooming itself makes the complete picture
(the forest/multifactorial issue) unreadable. Contextually, better understanding of
the complexity in medicine is not guaranteed by “precision medicine” itself. Advanced
health care demands a close cooperation between all issue-related fields, integration
of multidisciplinary knowledge and innovative technologies based on long-term strategies
and concepts considering interests of patients, professionals and society at large
Predictive, preventive and personalised medicine (PPPM)
The paradigm shift from “unPPPM” to “PPPM”
The above described great plurality of approaches indicates a broad understanding
of clear deficits which do exist in currently applied medical services and attempts
of diverse professional groups to remedy the deficits. On the other hand, there is
an increasing level of understanding that persisting deficits carry a fundamental
character and, therefore, cannot be solved by superficial modifications of health
care systems facilitating individual technologies such as “cancer genomics” by “precision
medicine.”
Global deficits are well-defined and described elsewhere as unpredictable, unpreventable
and impersonal medicine [20, 21]. It is evident that a paradigm shift is needed to
move from “reactive” to “predictive, preventive and personalised medicine” as a new
philosophy covering both “health care” and “disease care”, promoting an integrated
approach combining advantages of individual bio/medical fields and technologies and
consolidating a multi-professional collaboration.
New paradigm has been created by the EPMA experts as published earlier [22]—see Fig. 2.
Fig. 2
Paradigm shift from “reactive” to “predictive, preventive and personalised medicine”
Particular emphasis on ethics in PPPM
Sometimes, we, living in the XXI century, forget what was taught when the first universities
were established at the birth of XI century: “Never discuss about names,” “Never enter
an onomatomachia”, that is, never enter a fight (in ancient Greek, μάχη, máchi) about
names (in ancient Greek, όνoμα, ónoma). Sometimes, the meanings of the names “person-centred
medicine,” “individualised medicine,” “stratified medicine,” “precision medicine,”
“personalised medicine,” etc. are not so sharp; sometimes, they intersect, but it
is not clear until which point.
This is not a void and abstract “philosophical” question (actually, over the centuries
and the millennia, the philosophers never thought that a question of names was a genuine
philosophical question). This is a matter of money, a matter of grants, and a matter
of power. This means that the onomatomachia now occurring in the field of contemporary
biomedicine is actually a war for money and for power. But the citizens, in particular
a subset of them, that is, the diseased citizens, are totally disinterested about
it, even if, unfortunately, negative side effects of this war affect them. Citizens
are interested in a personalised care, whatever this could precisely mean [23].
This means that beside a scientifically well-founded medical approach facing their
unique potential or actual disease, they wish that their unique biography could be
taken into account as well. Yet let us put aside for a while the biographical part
(i.e. the age, gender, cultural, ethnic, religious, socio-economic diversity) of an
actual or potential patient, even if we know, from epigenomics, that patients’ lifestyles
and the environments in which they live are extremely impacting their quality of life
and their actual or potential diseases. Let us focus on the “medical” part.
A citizen with an actual or potential disease wants a medicine in which he/she is
at the centre, a medicine which is tailored on his/her polymorphism, a medicine which
is able to provide him/her with the right therapy, in the right dose, at the right
moment, for the right period of time. But he/she also wants a medicine which is able
to predict and prevent possible diseases. He/she is not interested in the way in which
this kind of medicine is called. But he/she is interested in understanding why it
is called in that way, in order to appreciate its potential ability to restore health.
And this is the real advantage of speaking in terms of predictive, preventive and
personalised medicine: the actual or potential patient understands what is going on!
Nevertheless, there is something more. The PPPM lends itself to an over-arching umbrella
under which the main ethical issues of contemporary biomedicine could be positively
tackled. Certainly, a predictive and preventive approach could imply several ethical
problems linked, for example, to overdiagnosis and overtreatment, detection of incidental
findings, psychological burden and severe existential choices connected with the knowledge
of the probability of a possible disease affecting us or our offspring and lineages,
or connected with our reproductive choices, etc. Contextually, PPPM plays a crucial
role as the optimal medical partner of a serious ethical counselling (and here, the
patient’s biography plays its main role) offered to actual or potential individual
patients, in order to empower them to make an infirmed choice about the diagnostic,
surveillance or therapeutic path to take, especially whenever these paths intersect
ethical or existential problematic situations that they have to solve [24].
Towards scientific excellence and practical PPPM implementation: special professional
focuses by the EPMA
This subsection is based on the well-elaborated PPPM aspects evidently advancing medical
sciences and health care. Corresponding professional statements have been approved
by the association within the fundamental document resulting from the EPMA Summit
2014 under the auspices of the presidency of Italy in the EU [6].
PPPM in cancer: the key questions puzzling medical sciences and advancing health care
The majority of people may carry hardly detectable micro- and asymptomatic tumour
lesions as it has been demonstrated by a series of detailed autopsy studies. However,
those lesions do not necessarily progress into clinically manifest oncologic diseases.
Furthermore, there is a phenomenon of the so-called metastatic inefficiency, due to
less than 1 % of all disseminated and circulated tumour cells which have a potential
to form secondary and distanced tumours (metastatic disease) [25]. Contextually, the
key question puzzling modern predictive, preventive and personalised medicine in oncology
is how to predict and effectively protect against clinical manifestation of the disease
by distinguishing between “silent” carriers of tumour lesions and patients who are
predisposed to a disease development and progression. The clue might be a “fertile”
microenvironment that effectively supports the tumorigenesis, tumour invasiveness
and aggressive metastatic disease [26]. The mechanisms “fertilising” the microenvironment
for the cancer advancement are well-addressed by innovative PPPM strategies in cancer
[26–29].
PPPM advancements in CVD management: a global health issue
Currently, the CVD-related health burden is the most severe in developed countries
and becomes overgrown in developing countries as well. The main reason for that is
that the chronic disease stages, multifactorial diseases and comorbidities are not
adequately addressed, since they do not follow the PPPM principles in currently practised
health care systems [30]. An advanced CVD management is needed at both population
and individual levels considering complex cardiovascular risk factors, co-morbidities,
individualised patient profiles, optimised screening programmes and innovative preventive
strategies. Chronic suboptimal health conditions such as primary vascular dysregulation
(Flammer syndrome) may be relevant for a number of predispositions and severe pathologies
with poor outcomes [31–33]. Consequently, the promotion of PPPM in CVD management
is a global health issue [34–36].
Global epidemic of diabetes type 2—twenty-first century disaster and PPPM solutions
Current epidemiologic studies report about over 400 million of diabetes mellitus (DM)
diseased patients worldwide. A big portion of DM cases remains undiagnosed. More and
more teenagers are affected by DM type 2. The global epidemic of DM type 2 places
an alarming burden on health care systems. The consequent challenges and costs overload
both developed and developing countries and economies. An effective implementation
of PPPM concepts to diabetes care is due long ago. EPMA emphasises the need to address
the all-encompassing complex approach for population screening, primary, secondary
and tertiary care benefiting non-diseased individuals, predisposed subgroups and affected
patient cohorts including those with comorbid pathologies such as CVD, cancer, and
neurological, neuropsychiatric and neurodegenerative diseases (NNND) amongst others
[6, 35, 37, 38].
PPPM advancing the comprehensive area of NNND
In a very few years, NNND are predicted to represent the majority of socially and
economically devastating disorders and diseases. Multifactorial physical and cognitive
disability of NNND-affected patient cohorts results from individual interplay of genetic,
epigenetic and environmental risk factors. Contextually, the comprehensive area of
NNND demands new strategies which would create a robust platform for the cost-effective
medicine of future NNND management [39–42]. Consequently, the advanced PPPM concepts
do place particular emphasis on primary prevention by the identification of predisposed
individuals, improved patient stratification and treatments tailored to the person
[6]. However, new regulations and innovative reimbursement programmes are mandatory
to prompt an effective implementation of the above listed concepts.
Rare disease (RD) management: proof-of-principles for personalised medical care
Although an entire spectrum of RDs affects many millions of people worldwide (e.g.
in Europe, there are at least 30 million patients), currently, no appropriate diagnostic
and treatment approaches are available for most of afflicted with individual RDs.
The majority of RDs can be diagnosed in prenatal and early postnatal periods. Due
to the genetic background of most RD pathologies, the multimodal diagnostic and treatment
approaches propagated by PPPM are instrumental for personalisation of RD management
[43].
Ancient medical traditions “reinforced” by innovative PPPM concepts
PPPM creates a unique platform for “reinforcing” traditional approaches of the ancient
medicines (TCAM). PPPM-TCAM hybrid demonstrates a great potential in person-centred
and participatory medicine, disease prediction in individuals with suboptimal health
condition, targeted prevention and individualised treatments. If properly designed,
PPPM-TCAM approach may be of particular value for health care systems that empowers
communities and individuals [3, 44].
Application of PPPM to the pain management benefiting all medical fields
Pain management is the central issue for a variety of syndromes, acute, chronic and
systemic disorders. Pain diagnostics and treatment are highly individual involved
in a wide spectrum of suboptimal health conditions, early and advanced stages of developing
pathologies and collateral diseases such as CVD, NNND, diabetes, and cancer. Application
of PPPM concepts to advanced pain management demands multidisciplinary expertise considered
in the context of improved health care economy and policy and direct benefits to the
patient [45–47].
Impacts of the oral and dental health: novelty by PPPM concepts
On the one hand, dental diseases are frequently caused by systemic disorders such
as diabetes mellitus. On the other hand, dental and oral pathologies are both early
indicators and risk factors for a variety of multifactorial diseases. This includes
pre-term birth, a spectrum of vascular pathologies, stroke, heart and lung disease,
diabetes mellitus with comorbidities, some types of cancer, neurological disorders
and several mental disorders such as depression, anxiety, anorexia and even bulimia.
Therefore, investigation of the cause-and-effect relationships between oral and dental
diseases on the one hand and multifactorial systemic disorders on the other hand is
a prerequisite for predictive, preventive and personalised medicine in the multidisciplinary
fields of dental and oral health care [48–52].
Environmental factors in a sensitive balance between health and disease
There is a highly sensitive interplay between a genetic component, epigenetic regulations
and environmental factors that determines a sensitive balance between health and disease
in individuals. Unfortunately, environment is still a largely neglected topic in health
care. PPPM approach aims to develop an appropriate knowledge and technological skills
for promoting affordable strategies in the emerging fields of environmental risk factors,
epidemiology, healthy lifestyle, individualised nutrition, food technology and culture
in a framework of cost-effective health care [29, 47, 53–55].
Robust PPPM platform to advance regenerative medicine
Prediction and personalisation in regenerative medicine are prerequisites for improved
individual outcomes. Hence, in order to optimally match the donor to recipient and
assess individual risks, a successful transplantation requires valid pathology-specific
pre- and post-transplantation biomarker panels tailored to the individual. Long waiting
lists of patients worldwide reflect major problems and current deficits, which require
PPPM-related solutions advancing this medical area on the global scale [6]. Individual
components of the overall management leading to substantially increased allograft
survival and decreased patient morbidity are an improved donor-recipient matching,
individual risk assessment for chronic allograft damage, prediction of graft accommodation
and creation of personalised immunosuppressive algorithms.
Body culture and sports medicine (BCSP) effectively promoted by PPPM
PPPM strategies in BCSP are based on optimisation of the relationship between individual
genetic predispositions and modifiable risk factors (nutrients, physical activity,
lifestyle, etc.). Therefore, the main tools are individualised physical exercises
and therapy algorithms, healthy balance between body tension and relaxation, optimised
sleep algorithms according to individual circadian rhythm, innovative rehabilitation
approaches, amongst others. Anti-doping control and effective measures are mandatory
for PPPM implementation in advanced BCSP. High-quality research based on measurable
effects utilising multilevel biomarker panels is effectively promoted by PPPM in BCSP
with a particular focus on individually tailored interventions [56–59].
Translational medicine: a powerful bridge between PPPM science and implementation
There are many scientific fields which, on a daily basis, provide a great knowledge
potentially useful for advanced medical services. However, a number of scientific
articles and valuable patents remain unused. The “bottleneck” between the sciences
and application has many reasons including economic circumstances and missing political
regulations. In order to effectively promote the translational medicine as the “catalyser”
for practical implementation of the accumulated scientific achievements, EPMA creates
a robust platform for an effective dialogue between PPPM relevant professional groups
on the one side, and industry and policy-makers on the other side—for more information,
see the main documents of the association [6, 35]. The main goal is to translate knowledge
from studies at the bench side to care at the bedside by following mechanism: from
discovery to health application, to evidence-based guidelines, to advanced health
care services and finally to health impacts for the patient [60, 61].
Information and communication technologies (ICT) resulting in cost-effective modernisation
of health care
A holistic presentation of individuals and discoursed health condition by ICT approach
implies a redesign of health care services. The ICT support is the prerequisite for
an effective PPPM by disease modelling, individualised patient profiles, optimised
diagnostic and treatment approaches. The ICT tools include mathematical modelling
methods, such as probabilistic relational models and process models, prediction of
a disease development, precise patient stratification, creation of the multimodal
diagnostic approaches, elaboration of the best possible therapy algorithms, an estimation
of individual outcomes, distanced patient monitoring, advanced avatar technologies,
and bid data management amongst others. Contextually, ICT is anticipated to result
in profound and cost-effective modernisation of health care benefiting the patient,
health care providers and society at large [28, 29, 62–66].
The crucial role of multilevel diagnostics in PPPM
Accumulating evidence demonstrates that an ideal biomarker does not exist. The role
of multilevel diagnostics is to provide maximum clinically relevant information by
utilising pathology- and stage-specific biomarker panels at the level of medical imaging,
subcellular imaging, multi-omics and relevant hybrid technologies. Integrating this
information allows for targeted prevention and personalised treatment regimes, avoiding
unnecessary drug toxicity, decreasing negative side-effects and reducing morbidity
[27–29, 62, 67–69].
Laboratory medicine in PPPM concepts: from passive assistance to active advising
Delayed intervention, untargeted medication, overdosed patients and ineffective treatments,
amongst others, are the deficits in currently pursued medical services that demand
a revised role of laboratory medicine in health care systems. The laboratory services
should become more complex, advancing multifactorial analysis. Such a complex analytics
should result in recommendations and active advising for clinicians in order to more
accurately interpret health-related data of the individual/patient. Therefore, an
effective ICT support (see the “Information and communication technologies (ICT) resulting
in cost-effective modernisation of health care” section) is mandatory. Practical implementation
of novel and complex laboratory tests certainly should be considered from the viewpoint
of their reasonability, cost-effectiveness and value added to a data interpretation.
Smart laboratory investigation strategies and all-encompassing data interpretation
are essential for an appropriate relationship between laboratory medicine and clinicians
acting hand-in-hand as the decision makers responsible for better individual outcomes
[70–75].
Well-regulated biobanking and biopreservation is pivotal for future progress in PPPM
For the future progress in development of novel biomarker panels, predictive and prognostic
technologies and personalisation of treatment regimes, an internationally valid biobanking
and biopreservation are essential. A proper creation of that is currently an ongoing
process in PPPM [66]. Considering individual types of biological material (tissue,
saliva, blood and cell samples, DNA, RNA, proteins, metabolites, etc.), the major
challenges are due to:
Consideration of ethical aspects including privacy- and security-related issues [76,
77]
Adequate national and international regulations
Optimised protocols for collecting, storing and retrieving the samples
High analytical quality of all the process of biobanking and biopreservation
Adequately organised clinical/patient databases.
An effective support by the advanced ICT systems for smoothly run processing and adequate
data interpretation is crucial for the clinical utility of biobanks [66].
Design of professional interactome in PPPM
PPPM carries highly multi- and interdisciplinary character and demonstrates high level
of international cooperation. Consequently, related networking demands an effective
interaction amongst professional groups as well as between health care professionals
and patient groups and policy-makers. All these groups currently do “speak different
languages,” which may create some communication barriers, however, reinforcing each
group’s perspective to reach higher level of understanding and cooperation in PPPM
framework. The specific output of this design activity is the so-called professional
interactome [78]. The PPPM-related interactome represents the most optimal model of
health care organisation with significantly increased quality of multilevel communication
and cooperation resulting in improved individual patient outcomes and health care
economy (see the “Advanced business models for PPPM concepts in health care” section).
Education as the heart of the PPPM-related scientific excellence and successful practical
implementation
The ultimate goal is to create a new culture in the health care sector and to promote
high level of professionalism by new generations of healthcare-givers who will be
capable to implement an all-encompassing approach to patient care recognising the
complexity and individuality of the human being. In order to promote innovative educational
programmes, the following worldwide pioneer initiatives have been developed:
The EPMA Journal regularly updates information about medical innovations and advanced
health care providing expert recommendations in predictive diagnostics, targeted preventive
measures and individualised treatment algorithms (https://epmajournal.biomedcentral.com/
and http://www.springer.com/biomed/journal/13167).
Advances in predictive, preventive and personalised medicine (http://www.springer.com/series/10051):
this book series, launched in 2012, provides an overview of complex strategies, innovative
technologies, novel biomarker panels, and multidisciplinary aspects of advanced biomedical
approaches in individual PPPM areas and health care as a whole. New technologies and
guidelines are provided for medical ethics, early and predictive diagnostics, targeted
prevention, treatments tailored to the person, health care organisation and economy.
This book series is intended to serve as a reference source for multidisciplinary
research and the health care industry with special emphasis on advanced health promotion
and cost-effective treatment of diseases.
Advanced business models for PPPM concepts in health care
If left unchanged, a long-term poor cost-effectiveness may lead to economic collapse
of current health care systems with persisting archaic business models. Across Europe,
there is a great diversity of systems, payment models and reimbursement schemes in
health care [72]. This imposes a highly fragmented market. On the one hand, there
is a need for policy dialogue in order to achieve improved structure and delivery.
On the other hand, advanced business models are required, in order to motivate
Healthcare-givers to apply more individualised diagnostic and treatment approaches
Healthy individuals and patients to accept greater responsibility towards their own
health condition
Industry to create novel products for health support, promotion and monitoring
Policy-makers for smart long-term regulations in health care sector such as an effective
promotion of increased health literacy in population, advanced screening programmes
and new reimbursement models for individual subpopulations and professional groups
Finally, the society at large to reinvest budgets focused on the most cost-effective
health promotion and primary health care.
In view of economic strain and the ageing populations, PPPM-related innovation in
health care systems is critical for keeping the high quality of health care affordable
and sustainable on European and global scale. Since its very beginning, EPMA is systematically
working on the economy of PPPM that is pivotal for advancing health care on European
and global scale [6, 8, 20–22, 28, 30, 35, 37, 40, 71, 72, 79–82].
Conclusions and expert recommendations
Concluding remarks are summarised in Table 1 in form of advantages and limitations
listed for individual types of medicines analysed in this paper followed by recommendations
for their most optimal application.
Table 1
Conclusions and expert recommendations
Term
Advantages
Limitations
Optimal application and unique niche
Traditional, complementary and alternative medicine, TCAM
Increases the own repair capacity of the human body; deals with natural products and
physiological approaches; is dedicated to disease prevention and well-being; highly
effective at the level of suboptimal health condition
Less effective for disease care; in manifest pathologies can be applied to complement
conventional treatments such as surgery, chemo-therapy, etc.; cultural barriers can
exist when TCAM is introduced by the country of origin to other countries with sufficiently
different cultural habits
➢ Diagnosis and treatment of suboptimal health conditions➢ Cost-effective preventive
medicine➢ Emphasises well-being➢ Pain management➢ Complementary treatments➢ Cultural
traditions of the country of origin
Person-centred medicine, PCM
Promotion of health as a state of physical, mental, social and spiritual well-being;
potential for disease reduction; emphasis on science and humanism; PCM promotes approaches
to health improvement, respect and responsibility at individual and community levels
Realisation of the ideals promoted by PCM demands clear definitions and validated
strategies
➢ Health care philosophy➢ Mental maturation of society at large➢ Integration of sciences
and humanism➢ Promotion of health➢ Promotion of respect and responsibility in the
society
Individualised medicine, IM
IM propagates a holistic approach by acknowledging multidimensional interaction between
internal and external risk factors which vary from individual to individual.
IM is clearly focused on individualisation of standardised intervention, but it provides
less developed concepts of predictive and preventive medicine, if any.
➢ Holistic approach to standardised intervention➢ Patient categorisation and modelling
Stratified medicine, SM
More targeted treatments according to individual patient subtype; stratified treatment
algorithms
Although being an extremely important instrument, SM represents just one step towards
“personalised medicine.”
➢ Cohort subgrouping➢ Patient stratification
Personalised medicine, PM
Actually considered best possible medical treatments adapted to the needs of the patient
Concepts of PM are adapted to “disease care” but not to “health care.”
Semi-personalised medicine compromising between standardisation and individualisation
in medicine
Precision medicine, PrecMed
PrecMed attracts attention of policy-makers to problems persisting in medical services;
additionally released budgets in medical sciences; increased publicity for disease
care; potentially increased cooperation level between individual medical fields
Politically motivated initiative utilising advantages of already existing and above
listed approaches; strong limitations by selectively promoted technological focuses
(e.g. genomics); unclear integration strategies in medicine; unclear cost-effectiveness,
benefits to individual patient cohorts and overall health care economy
➢ Potentially improved clinical impacts of specific areas such as genomics➢ Potential
technological integration in medical fields➢ Potentially improved outcomes in some
patient cohorts
Predictive preventive and personalised medicine, PPPM
PPPM is a really complex all-encompassing approach combining advantages of the above
listed individual approaches and minimising their specific disadvantages; clear concepts
demonstrating the highest level of maturity; the most optimal strategies considering
interests of healthy individuals, subpopulations, patient cohorts, health care systems
and society as a whole.
PPPPM is considered as the “medicine of the future” which needs the paradigm change
for entire spectrum of medical research and services, improved professional and general
educational levels, new economic and application models for both disease and health
care.
➢ Desirable versus current health care systems➢ Predictive medicine➢ New spectrum
of screening programmes➢ Targeted prevention➢ Currently unmet needs of healthy subpopulations
and patient cohorts➢ Cost-effective medical services and optimised health care economy➢
New dimension of professional interests➢ New scale of the knowledge integration➢ Highly
motivated technological innovation➢ Highly motivated interdisciplinary and multidisciplinary
cooperation➢ Individualised patient profiling➢ Active participation of patients in
the health care process