perspec tives

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opinion Should Pharmacometrics Be Training the Next R&D President? JVS Gobburu1 We continue to train pharmacometric scientists primarily in methodology. The lack of training in business and drug development concepts, however, is preventing pharmacometricians from becoming high-level decision makers. The more recent growth of opportunities in pharmacometrics is propelled by applications within both companies and regulatory agencies. However, these applications themselves may not lead to sustained growth of opportunities. How can we prepare pharmacometricians to fundamentally re-engineer the drug development paradigm? The preamble

Sustaining innovation leads to new technology for existing services and processes to make organizations more competitive.1 Performing bioanalysis or creating tables, listings, and figures for a clinical trial are services essential for pharmaceutical operations. Technological innovations (e.g., colorimetric assays to mass spectrometry) improved the quality and speed of bioanalysis. With disruptive innovation, a product or process takes root initially in simple applications at the bottom of a market and then relentlessly moves up, eventually displacing established competitors. Generally, disruptive innovations use off-the-shelf components integrated into a product architecture that is often simpler than previous approaches. In my opinion, pharmacometricians can champion disruptive innovation of the drug development paradigm.

What might disruptive innovation look like? Drug development practices have not changed fundamentally since the 1970s, despite an exponential increase in information. A recent report indicates that reduction in the phase II attrition from the current 66% to 50% could reduce the development costs by $1.33 billion.2 To achieve this cost reduction, pharmacometricians can lead the adoption of a continuous decision-improvement (equivalent to continuous process improvement) paradigm. In this paradigm, both the compound and knowledge (pertaining to compounds, disease, and trials) are considered assets. For instance, projections of drug effect on the clinical end point and net present value could be constantly updated as new knowledge becomes available. Knowledge from varied sources (e.g., in vitro potency of a new chemical and postmarketing data for a marketed drug) must be integrated to synthesize such projections. Pharmaco-

metricians can certainly provide the scientific support. But the key contribution of pharmacometricians toward any paradigm shift should be in managing the culture and navigating through the barriers to change. Are we training such leaders? Pharmacometrics employs biological, pharmacological, engineering, statistical, bioanalytical, and clinical theories or technologies (off-the-shelf components) to effectively analyze data to generate knowledge (generalizations), which can then produce intelligence (actionable knowledge). Several of the analyses can be performed by other quantitative scientists. Technological innovations are not the principal product of pharmacometrics, but paradigm innovations could be. The goal of our training should therefore be to produce scientific leaders who can alter the drug development or clinical decision paradigm. Training on techniques is important to form the scientific basis but is insufficient to create a market expansion on its own. The more recent growth of opportunities in pharmacometrics is propelled by applications within both companies and regulatory agencies.3,4 As a community we should decide if we want to train more scientists who can revolutionize the drug development paradigm. Both pharmacometrics and pharmaceutical research and development (R&D) will benefit if training is tailored to incorporate disruptive innovation into drug development and clinical decision processes. Training plan

A brief history and the current state of the field of pharmacometrics has been described previously.5 The focus of the early phases of pharmacometrics evolution has aptly been on methodology. Future growth in pharmacometrics can mean increased opportunities to influ-

1Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA. Correspondence: JVS Gobburu ([email protected]. edu)

doi:10.1038/clpt.2014.68 Clinical pharmacology & Therapeutics | VOLUME 95 NUMBER 6 | JUNE 2014

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Figure 1 Two potential paths for the professional development of future pharmacometricians.

ence high-level strategic decisions in drug development, expanded client base (e.g., commercial departments seeking pharmacometricians), and higher demand for pharmacometrics by project teams. Figure 1 shows two potential paths for the professional development of future pharmacometricians. The first path leads to technical mastery, which can aid methodological advances. The second path leads to mastery of drug development strategy to influence key decisions. It is important to note that the core training is common for both paths. The technical path can involve more advanced methodology training. Such scientists can aspire to be thought leaders. Most of our training programs are geared toward producing technical experts. In my opinion, a typical pharmacometrics project follows what can be called the D-I-A process. The first step is to state the decisions (D) to be made (or the key questions to be addressed). Subsequently, the appropriate information (I), consisting of data and domain expertise, is sought and subjected to quantitative analyses (A). The process is iterative, as decisions are made by interdisciplinary teams. Thus, the analysts also need “soft” skills (e.g., strategic communication, negotiation) to influence decisions. Developing strategy skills requires mastery of D-I-A principles upon completion of the core training. Subsequently, scientists should choose the disease or drug development (including regulatory) track for further training (see Figure 1). This is followed by hands580

on experience at a company, regulatory agency, or hospital. Such experience provides opportunities for a scientist to transform into a scientific strategist to influence key decisions. Companies are the top recruiters of pharmacometricians. Several companies have dedicated pharmacometrics scientists in their clinical pharmacokinetics or pharmacology departments. Fewer companies have a separate pharmacometrics department. From my observation, a majority of companies involve pharmacometricians in performing modeling and simulation tasks—not in drug development. That is, pharmacometricians are not part of the drug teams, which limits their opportunities to learn the art of drug development and subsequently teach others. Initially, the new recruits should gain drug development as well as pharmacometrics experience. Gradually these scientists will need to be coached to influence key decisions with the long-term goal of leading clinical development teams. It is only through such involvement that pharmacometricians can position themselves to innovate on the development paradigm. Participation in diverse programs (e.g., portfolio management, due diligence) can enable pharmacometricians to be eligible for the R&D president position. There is a grave need to fundamentally adapt the training goals to produce more scientists on the strategy path. However, the principal challenge in implementing this training is that most academic faculty

members are not trained in drug development. Educational institutions will need to seek diverse experts from other departments or pharmaceutical companies to help train pharmacometricians. In conclusion, pharmacometrics is not about number crunching but is, rather, a means to accomplish disciplined decision making. In my opinion, our workforce is populated with more technical-track graduates and a negligible number of strategy-oriented graduates. We need to train more pharmacometricians who can induce disruptive innovation of the drug development paradigm. Bringing on such a revolutionary change is not easy; we will need to overcome cultural and organizational barriers. As a community, we should first decide if we want to train more scientists who can revolutionize the drug development paradigm! CONFLICT OF INTEREST The author declared no conflict of interest. © 2014 ASCPT

1. Christensen, C. Disruptive innovation . 2. Paul, S.M. et al. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov. 9, 203–214 (2010). 3. Milligan, P.A. et al. Model-based drug development: a rational approach to efficiently accelerate drug development. Clin. Pharmacol. Ther. 93, 502–514 (2013). 4. Lee, J.Y. et al. Impact of pharmacometric analyses on new drug approval and labelling decisions: a review of 198 submissions between 2000 and 2008. Clin. Pharmacokinet. 50, 627–635 (2011). 5. Gobburu, J.V. Pharmacometrics 2020. J. Clin. Pharmacol. 50 (9 suppl.), 151S–157S (2010). VOLUME 95 NUMBER 6 | JUNE 2014 | www.nature.com/cpt

Should pharmacometrics be training the next R&D president?

We continue to train pharmacometric scientists primarily in methodology. The lack of training in business and drug development concepts, however, is p...
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