Aernoud Fiolet

374 Chapter 15 RECOMMENDATIONS FOR FUTURE PRAGMATIC TRIAL CONDUCT While the general aim of this thesis was to show efficacy of anti-inflammatory treatment in patients with coronary disease, it also serves the purpose of providing insights into pragmatic clinical research. Drug research and development come at extremely high costs and keep rising. This concept has been juxtaposed with the development of computer chips, described in a seminal paper byMoore. He correctly predicted an exponential increase in the number of transistors that can be placed at a reasonable cost onto an integrated circuit, doubling computer chip calculating powers every twoyears. 29 This principle was later eponymously dubbed “Moore’s law”. In contrast, drug development has evolved in a contrary direction, where the annual number of new drugs approved relative to the spending on research and development consequently halves every 9 years. Provocative, this concept has been named Eroom’s law (“Moore” spelled backwards). 30 (Figure4) The aetiologyof thediminishingyieldof scientific research per standardised investment is complex and entails elements of governmental, regulatory, methodological, and biological origin. 31 A consequence of this predicament is that conducting investigator-initiated research, without extensive sponsoring from a pharmaceutical partner, has become almost impossible. Repurposing existing drugs is not favoured in commercial research, since the return on investment cannot be guaranteed. This is exactly the hiatus where the scientific community has to take responsibility. Future sustainable trial conduct only seems viable with both commercial and government financial support. We provide recommendations based on the findings in this thesis. Firstly, we have shown throughout this thesis that a pragmatic trial design and a highly dedicated, small research team can still attain extremely high levels of patient follow-up. A risk-based model for clinical monitoring, one of the costly components of executing a trial, is very suitable when investigating existing drugs with known risk profiles. Secondly, the use of a central pharmacy rather than numerous local pharmacies provides a high level of safety oversight for a tenth of the cost, extremely reducing overhead costs. However, this can only be achieved when the regulatory authorities approve the construction of an extended trial arm for the distribution of study medication. Adapting government policies for this kind of research should help to provide innovative and generic pharmaceutical companies with a financial incentive to incorporate drug rediscovery in their