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Developing the Pharmacological Audit Trail

We developed the Pharmacological Audit Trail, a gold-standard system for evidence-based decision making during drug discovery and development, which uses biomarkers to track the effectiveness of cancer drugs and demonstrate that they are hitting their target.

Scientist in lab

Photo: Andrew Brookes, the ICR

Scientists at the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research, London and in our joint Drug Development Unit with our partner hospital, The Royal Marsden NHS Foundation Trust, developed the audit trail for a new era of modern precision therapies which target the molecular changes and abnormalities driving cancer cells.

Many of these therapies have since been shown to be more effective and cause fewer harmful side-effects than traditional cancer drugs which tend to affect all diving cells in more of a blanket approach.

Replacing out-of-touch approaches

Previously, drug development was geared to this one-size-fits-all mechanism of cancer treatment, with therapies all going through a similar set of pre-clinical tests before entering trials on diverse populations of patients.

Very little mechanistic evidence was collected during clinical trials – which made rational decision making very difficult. This approach was increasingly out of touch with advances in our understanding of cancer biology and in methods for investigating how drugs work in the body.

The Pharmacological Audit Trail (PhAT) was originally conceived as a framework for evidence-based drug discovery and development by Professor Paul Workman – now CEO and President of the ICR.

Working with clinical colleagues Dr Udai Banerji, and Professors Johann de Bono, Stan Kaye and Ian Judson, who are all based at the ICR and our partner hospital The Royal Marsden, he demonstrated the value of the audit trail in clinical trials of many different drug classes, including inhibitors of HSP90, PI3 kinase, AKT and HDAC.

Prioritising the most promising therapies

The technique makes intelligent use of biological discoveries and methods to thoroughly measure key performance indicators for drugs throughout their development, from the laboratory to the clinic.

This helps scientists to focus scarce resources on the most promising therapies, spares patients the side-effects of treatments that will ultimately not help them, and gives a truer picture of the effectiveness of a therapy in those patients it is designed to help.

And by monitoring biomarkers of drug response – for example, chemical signs in the blood, or the appearance of tumours on scans – scientists can make informed decisions about drug development without having to wait years to see the final results of large clinical trials.

At the ICR we're already seeing the results of the Pharmacological Audit Trail.

By helping scientists to focus their efforts on the most promising new therapies, and by ensuring that clinical trials are appropriately designed for personalised medicine, we are saving patients from needless harm, saving money by ending development of poor-performing therapies early, and ensuring that effective targeted drugs do not get shelved because of negative results in groups of patients they were never intended to treat.


Journal review articles on the PhAT by ICR scientists

The conceptualization and use of the PhAT by Professor Paul Workman and colleagues have been cited in textbooks

  • Takimoto CH, Wick MJ. Chapter 31 - Non-Clinical Drug Development A2 - Atkinson, Arthur J. In: Huang S-M, et al., editors. Principles of Clinical Pharmacology. 3rd ed., Academic Press; 2012. p. 517–29.
  • Eisenhauer EA, Twelves Chris, Buyse Marc E, Elizabeth A. In: Eisenhauer, editor. Phase i Cancer Clinical Trials: A Practical Guide. Oxford University Press; 2015.
  • Hait WN, et al. Chapter 27 - Personalized Medicine in Oncology drug Development. In: Hong WK, et al., editors. Cancer Medicine, Vol 8, 8th ed. USA: People’s Medical Publishing House; 2010.

Review articles by researchers external to ICR that highlight the PhAT