Kristin Carlsson Petri: How pharmacometrics modelling can augment and replace clinical trials

12/08/22 • 33 min

This week we dive into pharmacometrics as a discipline and the potential for replacing and augmenting clinical trials with modelling. We speak to Kristin Carlsson Petri, who is a Director of Pharmacometrics.

Pharmacometrics modelling is a range of mathematical modelling techniques that can quantify our knowledge of drug biology and disease as well as trial information. The power of the methodology lies in the integration of knowledge across drug development and different compounds.

Even though pharmacometrics modelling is coming of age in recent years, it is not a new discipline. Its origins trace back to work conducted in the ‘50s and ‘60s, and one of the modelling programs most commonly used today were built in the 1970s in the Fortran language. The development of computers and computing power has allowed the discipline to grow, since the modelling is highly dependent technology.

Now the regulatory bodies request pharmacometrics analysis and the FDA has its own unit that conducts pharmacometric analysis on the data provided. Both the EMA and FDA encourage inclusion of pharmacometrics analysis especially for paediatrics studies.

In paediatrics studies pharmacometrics modelling is especially powerful. This is an area where data is usually scarce and fewer patients. But this population should still be offered evidence based medicine. By drawing on existing data from adult studies, some of the gaps can be closed without additional burden on the patients.

There are several examples of regulatory bodies accepting label expansion into paediatrics without the need to run clinical trials - relying solely on evidence from pharmacometric models. This is an opportunity - since it takes typically 10 years from a drug being developed for adults to it being approved for children. Closing this gap will increase access to evidence-based drugs for paediatric patients.

The area could grow even faster if data sharing across especially pharma and academia could be accelerated, and AI and machine learning could be applied to it. This is difficult, since the legal challenges of sharing data blok an efficient exchange.

We also speak about datasets collected continuously from wearables, and how they are challenging some of the techniques developed in decades past - and how these may need to be updated to the new technological possibilities.

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Previous Episode

Temitope Keyes: Digitizing clinical trials from paper to decentralized trials

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For this episode we explore the evolution of the collaboration and partnership structure between sponsors, CROs and technology vendors in life sciences with Temitope Keyes, Executive Director of Encapsia. Temitope has had a front row seat to the digitization of the clinical trial process.

We speak about the paper handling system that used to characterise clinical processes, and how “validation” that we now use to refer to systems validation used to refer to the validation of the printed paper. An entire ecosystem of vendors was required to make the paper ecosystem function, and the debate back then was whether to in-source or out-source, say, printing.

The evolution away from paper was absolutely necessary to get an overview of what was actually happening in the trial. The safety issues with Vioxx is an example of how data buried in paper can endanger patients. Data submitted on paper also makes it prohibitive to find trends across trials and drug profiles.

Temitope takes us through the digitization arc of the clinical process starting from the phone-based IVR systems to manage drug supply. Next came the development of the clinical database. Pharmaceutical companies attempted to build them themselves, but the complexity also forced specialisation in the industry and the creation of many of the technology vendors we work with today.

Clinical operations is the most expensive part of a clinical trial budget, because it is human-intensive and humans are expensive. CTMS attempts to help provide an overview of the many people involved in a clinical trial.

As more and more systems started supporting the clinical processes, the cost became prohibitive. CROs entered the space to offer pieces of systems to sponsors for a lower price, and in that way became technology companies themselves.

We also speak about how we brought all the technology together to end-to-end solutions that allow decentralized clinical trials.

Guest:

Temitope Keyes: https://www.linkedin.com/in/temitopekeyes/

Encapsia: https://encapsia.com/

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Graham Dutfield: As drugs become more precise, so needs the patent system

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We speak to Graham Dutfield, professor of International Governance and author of That High Design of Purest Gold on the evolution of IP regulation in Pharma and how it could be transformed in the future.

Patents are a historic tool, but have undergone an evolution. Patents started out in the 1470’s in Venice, and as an example Christoffer Columbus had a patent to explore the new world. Only in the late 18th century did patents become associated with exclusive rights to exploit an invention in return for disclosing the recipe for it.

The purpose of patents is to incentivise companies to take on the considerable risk and heavy investment in researching and developing drugs. Without patents, competitors could replicate a successful drug without having to take on the investment and risk.

But even though the intention behind patents is to ensure further innovation, it also creates perverse incentives in life sciences. This is mainly because new uses of existing drugs can also be patented as well as human genes and other biologics.

We speak about how the biotech revolution changes the patent landscape by introducing complex technologies that require multiple patents to ensure protection to reap the benefits of the investment in their development. The industry is changing with a rise in the sheer volume of patents on both the drugs themselves, but also the manufacturing methods.

The professionalisation of invention - the intententive pursuit of invention - was in fact the greatest revolution of the pharmaceutical industry. We look back to the history of the pharmaceutical industry and how the centre of gravity changed from originally being centred in Germany, but moving to the UK and eventually the US - shaped by the world wars.

When turning to the future, we speak about the importance of biomarkers. They have the potential to transform medicine that works mediocre in the broad population to working exceptionally well in a specific subset of the population. There are also more approvals of novel drugs than in previous decades.

But there is still an issue with a lack of research in diseases in underserved populations as well as rare diseases, where the market for the drug may be small. The potential for technology transfer is also still unutilized, and getting this right might help us prevent another pandemic.

Graham envisions a menu of incentive structures for different kinds of disease areas that may differ for areas like chronic pain, antibiotics or rare diseases. That would be a more precise tool for getting the kind of invention we want in areas, that may currently be outside of the reach of patents.

Guest:

Graham Dutfield: https://www.linkedin.com/in/graham-dutfield-2013a91b5/

That High Design of Purest Gold: https://www.amazon.com/That-High-Design-Purest-Gold/dp/9811222479

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