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A novel approach of personalized medicine: considering multiple effects of a single drug

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Title:  A novel approach of personalized medicine: considering multiple effects of a single drug
Investigator:  Hiddo Lambers Heerspink 
Supervisor:   Dick de Zeeuw, 
Summary:   Type 2 diabetes is a major and rapidly growing health problem worldwide and is associated with considerable morbidity. Recent novel therapeutic strategies were not very successful in improving renal and cardiovascular protection. The explanation may lie, at least partly, in that drug therapy is not being optimized to the individual patient, but rather to a group of patients. Yet many drugs have multiple effects that vary across patients. Each of those drug effects may in turn affect the ultimate outcome in its own way. Hence, one may observe within a patient a drug-induced change in one parameter that may benefit a patient in the long term, but a drug-induced change in another parameter induces more renal and/or cardiovascular risk. These opposite effects (discordant responses) need to be taken into account. To enhance end-organ protection, the responses in multiple parameters in individual patients should be targeted and optimized. I propose integrating epidemiology and molecular biology approaches to investigate the clinical implications and underlying molecular mechanisms of the responses in multiple parameters in individual patients and to determine ways of optimizing them.
The project consists of two parts:

1. Data from large clinical trials with different drugs will be analyzed to investigate the consequences of different response patterns in individual patients on clinical outcomes.
2. Plasma and urine samples from a prospective study will be analyzed for an integrated computation system biology approach. Patient characteristics as well as proteomic/metabolomic measurements will be combined to dissect the underlying mechanisms of discordant treatment responses and to find ways to optimize them.
Financing: VENI (ZonMW)
Start:  1-01-2012
End:  01-01-2015 
  
Projects
The use of a multiple parameter response efficacy score to predict the effect of a drug on hard renal and cardiovascular
Diabetes Mellitus Treatment for Renal Insufficiency Consortium (DIAMETRIC) database 
System biology approach for discovery of biomarkers of renal disease progressioni in diabetes (SysKid)
PROVALID – prospective multinational cohort study in patients with type 2 diabetes treated in primary care
Vitamin-D deficiency as a risk marker for renal and CV complications in the general population
A novel approach of personalized medicine: considering multiple effects of a single drug
Optimal hard endpoints in clinical trials of renal disease progression
Albuminuria as surrogate endpoint in clinical trials
Individual therapy response to a sodium-glucose transport inhibitor
Involving patients in the assessment and evaluation of medication treatment
Groningen Initiative to Analyse Type-2 diabetes Treatment ( GIANTT )
The role of medication adherence in predicting treatment response and estimating cost-effectiveness of statin treatment
Pharmacogenetics and response to treatment of oral antidiabetics
Quality of prescribing: patient specific indicators that predict better outcomes in diabetes patients
Quality assessment of pharmacotherapy in patients with chronic kidney disease
Cost effectiveness of ACEi and ARBs on renal failure in diabetes patients
Drug information and risk communication in Africa
Regulatory Science Projects