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Predicting the potential cardio/renoprotective effect of a drug
The current drug development and registration practice in renal and cardiovascular (CV) disease management is focused on targeting a single drug towards a single renal or CV risk factor. The ultimate goal of the use of these drugs, however, is not to have a short term success in lowering (or raising) these so called risk factors, but to decrease the long term risk of renal or CV morbidity or mortality. The current mindset is such that we assume that if a drug has a positive effect on this risk marker, the patient will be protected for long term risk. Thus, the risk marker serves as surrogate or proxy for the intended effect.
To confirm that the drug effect on the surrogate or proxy matches the expected long-term efficacy and safety, the short-term trials are, or at least should be, followed by one or more (post-registration) hard-outcome studies involving clinically meaningful (hard) outcomes. The latter thus requires large and expensive randomized controlled clinical trials. In some cases these trials have a negative outcome, meaning that the drug is not delivering what it was intended to do and could even be proven harmful. This not only leads to late and costly attrition of potential new therapies, but also has consequences for the patient (long exposure to a drug which is potentially harmful), manufacturer (large loss of financial resources) and society (delay in new therapies for better healthcare, wasting of time and money). A possible solution would be to have a better short term estimate for the intended long-term safety and efficacy.
As stated, the short-term efficacy of a new drug is based on its effect on a single parameter, such as blood pressure. However, drugs have almost always multiple effects (beyond the intended target). It appears that many of these effects can also have profound influence on long-term cardiovascular and/or renal risk. Thus, to accurately assess the effect of a drug on long-term cardiovascular or renal outcomes, the effect on multiple risk markers should be taken into account. Previous studies conducted within the TI Pharma Escher project have shown that a tool based on the short-term change of multiple risk markers is much more accurate in predicting the long-term effect of a drug on hard renal or cardiovascular outcome than a short-term change in a single risk marker.
The Multiple Parameter Risk Response Score is a tool designed within the Escher project to predict the potential cardio/renoprotective effect of a drug of interest, based on predefined short-term responses in multiple risk markers. Within this Value Creation Call project, the score will be validated and tested for its usefulness by implementation and evaluation in regular health care settings. After implementation, the tool may help to reduce the number of negative or potentially harmful long-term studies, and may eventually even replace the expensive and time-consuming hard-outcome studies. The Multiple Parameter Risk Response Score will in this way lead to a more safe and rapid drug approval and a better patient care.
Full project title: Multiple parameter risk response score
Start date: 1 January 2012
End date: 31 December 2013
Goal: Validation of the Multiple Parameter Risk Response Score for reno/cardioprotective treatment
Principal investigator: Dick de Zeeuw
Project size: 3 FTE's
Project budget: 726 k
€ Partners: UMCG, UMCU, EUR, Abbott
“Running public-private partnerships is a profession by itself. TI Pharma is an excellent example of how you can do this in an effective way.”
Director/Secretary of the Medicines Evaluation Board