Adequate ends of personalized medicine
When taking a closer look at the ends of PM encountered in the literature (Table 1), the first main category listed is research. Basic research as well as “research” on new diagnostic and therapeutic measures is to be excluded from the ends of PM as it violates criterion 5: in the medical context,c research is always a means to a given end, but never an end in itself. Usually – although not always – the end consists in improving medical measures or to generate medical knowledge. Therefore it would not be consistent to include research as an end in a definition of PM.
The second main category is “drug approval” which neither is an adequate end for defining PM. After all, we search for a definition of individualized/personalized medicine. Accordingly, medicine is the genus of PM that denotes a main category to which a certain term belongs and which thereby specifies the limits of a term’s meaning. For instance, “hammer” belongs to the genus “tools” whereas “rose” belongs to the genus “flowers”. The genus “medicine”, however, does not imply the term “drug approval”. Rather, drug approval belongs to the genus “health policy”. Consequently, including drug approval in a definition of PM violates criterion 2 as it would imply an understanding of PM that transcends the genus “medicine”.
The category “further ends” is also inadequate for defining PM as the terms listed here are either too broad or too narrow. For instance, the ends of “decision making” or “reduce/control costs” do not even (necessarily) belong to the genus “medicine”, but rather to the genus “human action” or “business administration”, respectively.d As such they are far too broad to define PM adequately. Somewhat narrower, yet still too broad are ends like “patient management” or “use stratification”: it seems to be an end of almost every medical intervention to manage patients and use stratification. On the other hand, some of the findings categorized as further ends like “tailored wellness plan for individuals” are too narrow to define PM adequately: medicine necessarily transcends wellness as it ultimately refers to the health of patients while the term wellness targets only one aspect of health (if it counts as health related at all). For many diseases, increases in wellness will not result in improvements in health.
The remaining categories “health care”e and “improved health” are plausible candidates for inclusion. Before taking a closer look at their subcategories, we can generally exclude the subcategories “unspecified” from a definition of PM. To cut the argument short: all ends contained here are too broad to define PM adequately. Having said this, we will first turn to the subcategories “prevention” and “therapy”. To explain the argumentation underlying our decisions for exclusion, we have to take a closer look at the criterion of necessity (1): we assume that a new term becomes necessary only if changes occur or new discoveries are made that cannot be described by an already well-established term (for example, it was necessary to introduce the term “laptop” because the established term “personal computer” did not imply the mobility that the new device exhibits). Consequently, in the medical context, a new term is necessary if the ends and means of medical interventions change in a way that is not captured by any well-established term. Accordingly, the question is whether any of the subcategories of “prevention” and “treatment” necessitate the introduction of a new term. We argue that only categories speaking of improvements fulfill the necessity criterion. The other subcategories, e.g. “risk prognosis/prediction” or “primary prevention”, are already well-established terms which do not justify introducing a novel term. This holds for both the subcategories of “prevention” and of “therapy”. Accordingly, we excluded all subcategories except for the ones that refer to an improvement.
Across the categories included thus far we find subcategories that describe different dimensions of improvement: “effectiveness/efficacy”, “timing”, “tailoring”, “choice of treatment”, “efficiency”, and “safety”. Some of these specifications can be regarded as inadequate ends for defining PM because they violate the criterion of non-redundancy (4). In health care we are confronted with a hierarchy of ends. Certain ends (e.g. better timing of treatment) are not pursued for their own sake, but rather for the sake of certain higher-order ends (e.g. more effective treatment). To put it differently: effectiveness, efficiency and safety of an intervention are the dimensions that define improvements in healthcare. For instance, a medication is considered better as an alternative medication if it either results in a more effective treatment measured on some health-related indicator, has less side effects (safety) or is more efficient (i.e. costs less while producing the same health effect or has a bigger effect at the same costs). Improvements of treatment choices as well as of timing and tailoring always imply improvements on one or all of the dimensions “effectiveness”, “efficiency” and “safety”. Of course, improving treatment choices, tailoring and timing does not necessarily reach all of those higher-order ends. Nevertheless, they are the ultimate ends of any improvement in health care. Therefore, “effectiveness”, “efficiency” and “safety” are to be understood as a triad of ultimate ends of health care innovations that are implied in any adequate lower-order end. In accordance with criterion 4 we therefore excluded improvements in “effectiveness”, “efficiency” and “safety” from our definition as they are necessarily implied by any medical improvement.
Additionally, improvements in choices of treatment are themselves implied by improved tailoring of treatment. To be able to choose a treatment – or the right treatment, respectively – one needs to tailor the treatment to the specific (sub-)type of disease. An improvement in tailoring diagnostic, prognostic, or treatment measures therefore necessarily leads to an improvement in treatment choices which is therefore redundant and can be excluded. Left are improvements of tailoring and timing of preventive and therapeutic measures as ends of PM. Those ends, however, imply improvements in health as ultimate end of any improvement in health care. The category “improved health” can therefore be excluded from our definition in accordance with the criterion of non-redundancy (4) following the same line of argument (improved health as ultimate end is implied by improvements in tailoring and timing of prevention and therapy).
Consequently, only “improvement in tailoring and timing of health care” are plausible ends of PM. They satisfy criterion 4 and can be considered adequately distinctive (2), are neither circular (3) nor inconsistent (5) nor ambiguous (6).
Adequate means of personalized medicine
However, we did not show so far that criterion 1 is ultimately satisfied: an improvement could potentially render a new term necessary, but it does not necessarily. Ultimately, many changes introduced to the health care system aim at improving timing and tailoring of prevention or therapy. However, not all of them require the introduction of a new term (e.g. new screening interventions to improve timing of cancer treatment). However, as stated above, a new term becomes necessary if the ends and the means of medical measures change in a way that is not captured by any well-established term. Consequently, we have to examine whether we can find means mentioned in the literature which satisfy criteria 1-6 and thereby specify the ends in a way that criterion 1 is satisfied.
First, the subcategories “unspecified” are excluded based on a similar argument as brought forward above: all means contained here are too broad to define PM adequately. Furthermore, only the means “utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics” satisfy criterion 2. All other means in the category “application in the healthcare system” – excluding the category “usage of (specific) technology”f – are not adequately distinctive as they are means employed in any medical measure (e.g. questions concerning gender and weight should be part of any routine anamnesis). Those means – usage of information on the genetic, proteomic, metabolomic and molecular pathway level – are adequately distinctive and can, furthermore, be considered new in the sense requested by criterion 1: they indicate the necessity of a novel term that emphasizes their use in contrast to using standard information like medical history or other non-genetic biomarkers (e.g. blood pressure). One could criticize that we call the use of genetic information new and adequately distinctive as it has long been informing medical decision-making, especially in the context of prenatal diagnostics. However, recent technological developments have rendered it possible to extend the informational base to genomic information, epigenetic information or pharmacogenetic information and also further information on the influence of single genes. The genetic information relevant in our context is of a new quality. We therefore did not exclude genetic information on the basis of criteria 1 and 2. It furthermore satisfies criteria 3-6.
Combining ends and means: an adequate definition of personalized medicine
Accordingly, we can now derive an adequate precising definition of PM:
PM seeks to improve tailoring and timing of preventive and therapeutic measures by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics.
Although it is not clear whether improvement of tailoring and timing as ends satisfies criterion 1, tailoring and timing based on genetic/proteomic/metabolomic/molecular pathway-related information is conceptually new and therefore justifies a new term. Moreover, the definition satisfies criteria 2-6.
Several further remarks are important: First, it might not be clear why we have not included “research” as a means in our definition. As stated above, in the medical context, research is always a means for a given end where the end usually consists in improving medical measures or possibilities. In analogy to the argumentation concerning higher and lower-order ends, whenever medical measures, e.g. diagnostic tools, are applied, there usage is necessarily grounded on research. Hence, research is implied in any medical intervention or means – in the case of PM the use of information on molecular pathways, genetics, proteomics and metabolomics – and therefore has to be excluded from our definition in order to satisfy criterion 4.
Second, a similar point applies to the subcategory “usage of (specific) technology”: like any medical intervention, measures considered to be personalized utilize certain (specific) technologies. Our definition therefore analytically implies the utilization of specific technologies that allow for the measurement and evaluation of the respective biological information and biomarkers. “Usage of (specific) technology” must accordingly not be included in the definition.
Third, our definition contains “improving tailoring of prevention and therapy” as one end of PM. If this is understood on the individual level, tailoring becomes impossible and the definition would be useless: it is impossible to find the drug that works perfectly for a single individual. The processes we employ to test medical devices and pharmaceuticals are clinical trials involving patients groups
and not individual patients. Accordingly, tailoring means no more than stratification. In turn, stratification means the detection of sub-groups of patients that benefit from a certain measure. Tailoring treatment to a patient can therefore only mean assigning the patient to a certain sub-group of patients that appear to respond particularly well to a specific intervention. Against the background of these practical considerations, we can slightly adapt our definition:
PM seeks to improve stratification and timing of preventive and therapeutic measures by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics.
A final remark regards the part of the definition that refers to “improved preventive and therapeutic measures”. “Improved health care” is equivalent to “improved preventive and therapeutic measures” as prevention and therapy are what constitutes health care. To put it differently, improved preventive and therapeutic measures are implied in improved health care and vice versa. According to criterion 4, we can replace the former by the latter in the definition, but should not include both formulations. For reasons of efficiency of formulation we decided to include the latter arriving at the final definition:
PM seeks to improve stratification and timing of health care by utilizing biological information and biomarkers on the level of molecular disease pathways, genetics, proteomics as well as metabolomics.