Alle modules gegeven in Q8 Research lijn compleet samengevat met verhelderende illustraties, begrippen en voorbeelden erbij. Bevat de modules ''topics in personalized healthcare'', ''renal disorders'', ''Alzheimer and stress disorders'', ''nanomedicine'' en ''infectious diseases and global health''.
Radboud University, Nijmegen
Made by: Georgia Graat
,Research summary Q8
Topics in personalized healthcare
What does it mean?
Personalized healthcare means that, whenever possible, we match diagnostics and therapies to the
specific characteristics and needs of the patient to improve their quality of life and disease
progression. This is being improved and expanded by possibilities created by research and new
technologies. Personalized medicine as emerging practice uses an individual’s genetic profile and
specific biomarkers to guide decisions made in regard to the prevention, diagnosis and treatment of
disease. Within the Radboud, this is one of the top priorities that is being focused on in care of the
patient and development of new technologies.
Traditional medicine is only based on family history, socio-economic status
and environmental factors. Nowadays, we have more biomedical input
from genetic testing and proteomic profiling, which enables us to detect
individual differences. Variations can be detected as harmless (slight
change in phenotype) or harmful (disease). It may be very useful in a group
of patients with the same diagnosis, to establish whom the treatment
would be unnecessary or toxic for, and considering giving them another
treatment. The effectiveness and side effects of drugs are also very
dependent on the individual differences, determining the possibilty for
widespread population use.
This means in the current state, we have switched from reactive medical
care to efficient medical care. Reactive medical care entails that you have a standard protocol after
diagnosis of the treatments that you will use in everyone, and switch drugs if necessary. The new
paradigm includes screening and prevention based on determined predisposition risk. Based on
individual characteristics, the best drug can be selected immediately, decreasing the disease severity.
The future paradigm would include only preventive medical care combined with screening to make
sure none of the population gets ill.
Definition of evidence based medicine: the conscient practice to optimize medical decision making
based on the highest quality scientific evidence, determined from meta-analysis and systematic
reviews of RCT’s as these give unconfounded estimates of treatment effects. Evidence is more
important than beliefs by individual experts.
Definition of personalized medicine: tailoring of medical interventions based on predicted risk of
disease. It assumes that heterogeneity in disease is due to mechanistic differences between patients,
and that patients with similar symptoms may have either different etiologies or biology resulting in
different treatment outcome.
Made by: Georgia Graat
,Values and challenges
Personalized healthcare will provide us with better evidence for diagnostics and therapies. We are
able to test before we treat and thus get to the right drug the first time. Promises for the strategies
are, for prevention, earlier detection of patients at risk, for diagnosis accurate diagnosis that enables
individualized treatment, and for treatment targeted treatment with reduced side effects.
There are also some challenges that appear when we start using personalized healthcare strategies
more. Of course the rising costs of healthcare and other financial aspects should be taken into
account. The societal implications are considered health political questions and companies might
have policy or regulatory issues. A long term issue might be the increased risk having insurance
consequences, and ethical questions about moral dilemmas and solidarity might come up.
Organization of research
The Radboud has the medical center,
medical faculty and science faculty
working together on personalized
medicine. This healthcare is provided on
molecule, cell, organ, patient, and
population level, but the biggest impact
right now is made on patient level.
The three institutes within the medical
center are health sciences, molecular life
sciences and neuroscience. These
combined have 18 themes focused on
different aspects of the body.
There are certain types of research that contribute to personalized healthcare in general. As the
research covers the biomedical science from molecular to health system level, an immense variety of
different study designs is needed to answer the sub questions that lead to an intervention that
benefits individual patients and the society. These study designs can be divided into two views within
the medical science. The evaluationist emphasizes on discovery, explanation and testing of
hypotheses, while the discoverer emphasizes on evaluation of interventions and making hypotheses.
This means they differ in their thinking about the role of prior specification of a research question:
the evaluationist does this beforehand and tests it, but the discoverer produces one according to the
information from studies.
The evaluationist and discoverer differ in their research hierarchies, or study designs that they
believe are most promising. The hierarchy of design to obtain medical knowledge in a evaluationist
view is therefore: RCT – cohort – case-control – case series. This is because it aims for intended
effects of therapy, so which designs have the highest strength to prove an hypothesis. The hierarchy
for the discoverer is based on the sources most useful to make new discoveries and produce
hypotheses. This is case series – case-control – cohort – RCT. The first is more focused on
experimental research, while the latter is more epidemiologic research. Both contribute to
progressing scientific insight in their own way.
An evaluationist has to preplan ever aspect of the trial beforehand with the aim of the studies to
evaluate whether new therapies/diagnostics that looked good initially actually improve the patient’s
life. A discoverer tries to find existing data to check whether an idea they came up with due to the
Made by: Georgia Graat
, case of one patient or lab result also holds for other patients, and write a paper on the confirmation.
This gives more input for evaluationists to test in their studies. This does contain more bias as you
keep searching until you find a new hypothesis. A disadvantage of the evaluationist is the slower
progression of science due to preplanning. It is a form of quality control to produce numbers, but will
not give insight into a next step of reasoning.
Personalized intervention strategy
The development of a personalized healthcare intervention strategy is always aimed at having a
significant impact on healthcare. Required is that one has a thorough understanding of the etiology
and heterogeneity of a disease, but also the likely impact it will have on clinical practice. The
importance of the outcome of an intervention strategy depends on the validity of its assumptions
regarding the relevant disease mechanisms, and how it will integrate into the healthcare system. This
depends on the current clinical practice and the structure of the system, which results in the impact
of the proposed strategy.
An evidence based medicine recommendation would be to only look at studies and results of articles,
determine what is in general for the whole population the best and prescribe this to the patient. The
goal in this research is to find the average treatment effect on the treated. Personalized healthcare
recommendations would be to look if the characteristics of the patient are similar to certain studies,
and which individual characteristics (genetics, blood pressure, gender etc.) would improve/decrease
the health outcome. The goal is here to find the average causal effect of a treatment.
To identify relevant subpopulations and possible targets for treatment, we need biomedical
knowledge on genetic variations and biomarkers. DNA can tell us a lot about risk of a disease, effect
on the treatment and prognosis. One example is starting newborn screening on thousands of genes
to manage healthcare throughout someone’s entire life. This would mean by blood and tissue
samples obtainment, we would get a unique molecular profile to screen for cancer and neurological
diseases, and determine which treatments might work. Biomarkers are already being used to
support medical decision making in many ways.
- Identify certain causes in acute care setting
- Risk stratifying patients for preventive interventions
- Screening populations for early disease detection
- Subtyping disease to facilitate molecularly tailored therapy
- Monitoring response to and safety of treatment
A biomarker is defined as: a defined characteristic that is measured as an indicator of normal
biological processes, pathogenic processes, or responses to an exposure or intervention found in
blood, fluids, or tissues. A biomarker is thus a naturally occurring molecule, gene, proteins, or
characteristics in the body by which a particular pathological or physiological process can be
identified. Molecular, histologic, radiographic and physiologic characteristics are types of biomarkers,
but biomarkers are not an assessment of how an individual feels or functions. Examples are age
(cumulative exposure estimation and disease outcome), body temperature, blood glucose, single
nucleotide variation, and tumor volume. Socio-economic status and air concentration are definitely
not biomarkers.
Biomarkers can be diagnostic (presence and type), prognostic (outcome, recurrence), or predictive
(treatment response). They can be used from determining what causes the disease, indicating the
outcome of the disease to selecting the best suitable treatment. This combines to the personal
prognosis of a patient. A biomarker has to meet certain criteria to be considered good:
Made by: Georgia Graat
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