Challenge of Evidence in Individualized Medicine

Kathleen Kraft; Wolfgang Hoffmann


Personalized Medicine. 2012;9(1):65-71. 

In This Article

Stratification as a Link Between EBM & Individualized Medicine?

Some have argued that the concepts of EBM and individualized medicine are contrary[22] (Figure 1), but individualized medicine also has to be evidence-based.[23]

Figure 1.

Differences between evidence-based and individualized medicine.

Could both concepts usefully complement each other? Healthcare research cannot solely rely on large multicenter, placebo-controlled, randomized trials but increasingly need to consider routine data. The evaluation of routine data from health insurances and findings from large population-based cohort studies could help divide patients into relevant subgroups. An integration of study design with high internal validity (i.e., RCT) and high external validity (i.e., data from routine care) would provide grounds for an 'evidence-based individualized therapy' as a next level of EBM rather than a competing concept. Involving the individual patients' situation in clinical decision-making is what doctors have done for centuries. Looking at surgery EBM starts to fluctuate when looking at the individuality of patients. Comparing three patients: pancreatic carcinoma, stage IIA (characterized by spread of the growth of the cancerous tissues to the organs and tissues besides the pancreas, but it has not yet made any inroads inside the lymph nodes), all three patients will undergo surgery.[24] However, the first patient may be a 45-year-old woman suffering from cachexia with a BMI of 18 kg/m2. The second patient is a 52-year-old man with a BMI of 23 kg/m2, the third is a 78-year-old man with a BMI of 38 kg/m2, which is defined as obesity. Even though the patients' clinical situation is completely different, the operation method will be the same. The success of the operation will be largely determined by the patient's individual situation and the surgeon's expertise rather than by the evidence-based surgical procedure. In cases like this it is necessary to stratify patients according to individual factors rather than apply a standardized therapy, as guidelines are reaching their limits.

Stratification in this sense means a classification of the population according to certain characteristics that are relevant for the selection of therapeutic options. This is at the heart of individualized medicine. Evidence-based stratification results in subgroups of increasing homogeneity down to the level of individuals. This reasoning does not imply high-end innovative biomarkers or 'omics technology. Important clinical stratification items include comorbidity, multimorbidity, metabolism and genetic background as much as age, gender, social status, lifestyle and environment.[25,26]

When dividing any population into subgroups the specificity of the criteria used for stratification become pivotal as much as the algorithm that describes their relative impact and in various combinations. The more specific stratification algorithms are in generating diagnosis, assessment of disease risks and tailored interventions, the more targeted the therapeutic regimen will be. Hence, stratification of the population provides a link between EBM and individualized medicine.