A pharmacist in The Hague who reproaches the pharmaceutical industry about this is now producing his own copy of a standard medication. In an article in the 6 December 2017 edition of the Dutch newspaper Trouw, GP Hans van der Linde also argues that medication developers are only really interested in marketing and in buying up other people’s innovations. Pointing the finger and delivering reproaches are all well and good, but they won’t get medications to patients sooner and more cheaply. The fact is that being able to predict the potential success or failure of a new medication at an early stage can deliver substantial social benefits. TNO’s Peter van Dijken, Han van de Sandt and Wouter Vaes emphasize that TNO is currently working on various technological developments to bring this goal within reach.
The Council for Health and Society (RVS) recently published a report highlighting various issues with the current drug development model. The Council states that this development process can be made faster, better and cheaper. The development of new medications takes a very long time and involves huge sums of money. Also, many candidate medications turn out to be unsafe or less effective than expected, often at a very late stage in this process. During expensive clinical trials, nine out of ten promising drugs fall by the wayside. All of the costs incurred are then passed on in the price of those medications that do make it to the market.
Characterize preclinical models effectively
Why do so many candidate medications fail at such a late stage in the development process? According to Han van de Sandt, Research Manager Metabolic Health Technology, an important initial factor is an inadequate knowledge of the models used during preclinical efficacy studies. “All too often, chronic diseases are investigated in short-term studies, using models (or experimental animal models) involving disease mechanisms that are poorly understood. This makes it extremely difficult, if not impossible, to translate data from these studies into the human situation. One reason for this is that human physiology is extremely complex and another is that many diseases take a long time to develop.” The proper characterization of preclinical models is a worthwhile investment, as this reduces the risk of candidate medications failing during the expensive clinical phase. The same applies to non-animal testing methods, such as organ-on-a-chip, which simulate only a small part of an entire human being. Han explains that “If these models are used to address complex biological questions, such as those associated with drug development, it is essential to know what aspect of human physiology the model represents and which aspects it does not. An interesting new development is the use of human stem cells to explore each individual patient’s response to a candidate medication. If this technique can be perfected, it would lead to fewer, better designed clinical trials.”
“The proper characterization of preclinical models is a worthwhile investment, as this would reduce the risk of candidate medications failing during the expensive clinical phase”
Medication research could be further improved by taking more measurements – from a limited number of healthy volunteers – during early clinical trials. The use of specially developed early biomarkers, combined with increasingly sensitive measuring methods, means that effects can be identified at an earlier stage. Wouter Vaes, Senior Scientist in Microdosing and Microtracer Studies, explains that “Microtracing is a technique that involves administering minute quantities of medications to human test subjects. It can be used to explore ways in which the human body processes the medication and ways in which the medication affects the body. The earlier this is done, the sooner it will be possible to make a well-founded estimate about the candidate medication’s chances of success. That could result in huge cost savings.”
Modify international regulations
Peter van Dijken, Managing Director of Healthy Living, concludes that “Investing in better preclinical models and extensive early clinical trials can yield substantial cost reductions, while optimizing the development pathway leading to effective drugs. Time-honoured practices and international regulations must be modified to this end. This will require commitment by all of the stakeholders. The European Medicines Agency (EMA) is the body responsible for the scientific evaluation, supervision and safety monitoring of medicines in the EU. The Agency’s upcoming move to Amsterdam can also play a positive part in this.”
Han van de Sandt, Research Manager Metabolic Health Technology
Wouter Vaes, Senior Scientist in Microdosing and Microtracer Studies