Synergy between man and machine – the future of drug development


Robert Roe discovers that the future of drug development will increasingly rely on advanced software


tools that can not only produce and manage data but also help scientists to make better decisions


T


he failure of a candidate drug can cost millions of dollars in wasted research – for this reason many chemists are now turning to soſtware that not only


provides modelling or predictive capabilities but multi-parameter optimisation that can aid decision-making, leading to more efficient use of resources. Drug development is a huge business,


as successfully trialled drugs can generate billions of dollars in revenue. But for every successful compound, thousands of potential drugs fail. Te soſtware has been used to compliment and accelerate drug design for several years, but this still leaves chemists with complex and risky decisions to make when selecting potential compounds. Some of this risk comes from knowing


which compound or series of compounds to choose for a project but, as Optibrium’s CEO and company director Matthew Segall explains, uncertainty in the data – if not well managed – can lead to wasted resources. ‘Tere are a lot of different end-points


measured or calculated and many different compounds or chemistries a project will explore – but a point we emphasise, that we believe is underused, is uncertainty in data – very significant uncertainty,’ said Segall. Tis combination of complex parameters


for a drug development project – the uncertainty in data, and the huge list of potential candidate drugs – were primary factors that drove Optibrium’s decision to develop ‘decision analysis methods to help people navigate through a very complex


22 SCIENTIFIC COMPUTING WORLD


landscape of data,’ said Segall. ‘Te goal is to prioritise compounds and to understand the structure activity relationships that are driving activity and other properties within the chemistry. ‘Everyone knows the value of downstream


failure. If you pick the wrong chemistry and push it forward, you can end up with these incredibly costly late-stage failures.’ But Segall stresses this is a hidden cost, which is how many potential drugs have been missed, due particularly to the uncertainty in the data.’ Tis lack of understanding around uncertainty can lead scientists to make decisions that are not supported by the data that is available.


Multi-parameter optimisation As drug development projects become increasingly complicated with multiple parameters that need to be optimised, this uncertainty can be an acute stumbling block, or, as Segall explains, it can be used to a chemist’s advantage. ‘What is really unique about the approach


that we use is that we explicitly propagate the effect of that uncertainty through to the decision that is being made. We have published numerous papers on this. One of the things that we observed in a paper published in Drug Discovery Today around 2012 was the cognitive biases involved in decision making.’ ‘Tis is something that has been well


explored by experimental psychologists that


everyone, including scientists, find it very difficult to make decisions on complex data when there is a lot of risk and uncertainty involved. Helping people recognise and use uncertainty appropriately is very important and unique to what we do,’ said Segall.


Complementary software Drug development relies on a scientist’s ability to manage hugely complex streams of data on any number of compounds of interest to a particular project. To keep up with all of this data and make effective decisions requires the use of sophisticated soſtware that can alleviate some of the pressure from drug development projects. However, some companies recognise their


expertise lies in a particular area and so work to ensure complementary soſtware packages can work together, so users have the choice to pick and choose soſtware right for them. ‘We develop a lot of technology in-house,


but as a company we recognise that no one entity can develop all that is cutting edge in every area of computational chemistry and cheminformatics’ stated Segall. ‘We actively seek partners that are leaders in their space’ to bring the technology into their soſtware environment and make the interaction as seamless as possible for the end user.’ It is this acceptance and willingness to use


the best tools that creates an environment where several highly specialised soſtware packages can be used together to create an effective platform for drug development. ‘We have partnerships with Collaborative


@scwmagazine l www.scientific-computing.com


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