Keith Rodgers, expert in project management systems and current Chair of the Pharmaceutical Industry Project Management Group (PIPMG) speaks with Andrew Smith about project and programme management in clinical research.

A new report from Deloitte looks at the decline in Internal Rate of Return (IRR) across pharma R&D, and suggests that improving late stage success rates has a far greater impact than reducing cost or development times. We spoke to Hugo Cervantes, one of the leading contributors to the report, about what these findings mean, and what pharma can do to improve the situation, from closer collaboration to a sharper focus on value throughout the development process.

It doesn’t seem that the decision was made on the basis of the underlying science, or even the specific compound, being flawed. Indeed, less than a month ago the company gave a positive update on the phase 1 trial on its spinal cord injury treatment. Instead, the announcement spoke of “the current environment of capital scarcity and uncertain economic conditions” and that the decision was made “after a strategic review of the costs, value inflection timelines and clinical, manufacturing and regulatory complexities“, concluding that the move was necessary to ensure there was “sufficient financial resources to reach these important near-term value inflection points for shareholders without the necessity of raising additional capital.“  In short, they chose to focus on less controversial products that are further ahead in their development rather than a product stream with more question marks over its regulatory and political acceptability that might “kill the company” before making it to market.

This was, of course, a pragmatic and sensible decision for a publicly-listed company to make on behalf of its shareholders. However, it is a saddening decision for the science as a whole and sends a worrying message about the capability of the biomedical industry to pursue the step-change type of innovation that it needs in the long-term.

In the near future, companies need to replace their current portfolio of blockbuster drugs (which are effectively “one size fits all”, and were introduced with relatively few constraints on pricing) with a larger portfolio of products, with their price tightly linked to effectiveness in precisely defined patient groups. This presents a set of managerial and economic (and, to a lesser extent, scientific) challenges which, although complex,  are meat and drink for the analysts who drive the investment community. However, this line of development will only get us so far before we hit a barrier where the cost of demonstrating safety, efficacy and value at the individual level outweighs the revenue these products can realise. There is only so much more efficient our clinical development can be…

Then we will need entirely new technologies enabling us to address areas of therapeutic need that are otherwise effectively unmet, such as stem cell technologies. While Geron’s decision is probably the right move in difficult circumstances, it is imperative that it does not provoke the entire industry (or, more importantly, the entire investment community) to shift away from this area of research. Geron shows some degree of commitment to this with its intention to sell or license its stem cell assets to other players, but for this to succeed the investment community needs to have more courage in addressing the regulatory, political and commercial unknowns around stem cell products and to extend its horizon for a return on its investment in this important area.

In the current economic climate, this is a “big ask” but the long term consequences of not doing so would be worse all round.

• That increasing globalisation is inevitable as a strategic result of shifts in demographics of patient groups and capability of societies to pay for medicines;
• That this shift has been accelerated by tactical advantages around speed and cost of conducting clinical trials; and
• That, provided these clinical trials are conducted with cultural sensitivity and to globally accepted standards of procedural and data quality, this is a ‘good thing’.

But how close is the correlation between the buzz and the truth? There is undisputed interest in many “emerging” countries, but how long is it taking for reality to catch up? Indeed, when we say global, do we really mean global at all?

Recently, I chaired a stream on “managing study globalisation” at the first ICR Symposium. Speakers and delegates alike shared their experiences, interest and commitment to carrying out “global” clinical trials for good ethical, practical and commercial reasons. Many countries were mentioned, and many details were discussed around the intricacies of working in the BRIC countries (Brazil, Russia, India and China) etc. I gave a presentation to close the stream, sharing an analysis I had done of the locations of studies listed in www.clinicaltrials.gov. My conclusion was that, while the pool of countries being used in clinical trials is certainly expanding, and increased attention on these emerging locations is certainly justified, the rate of change is perhaps slower than many might think, and the pool of countries is only expanding by a relatively modest amount.

I compiled a list of the top 25 countries mentioned in all studies in the registry and compared it with studies registered since 2009. While the ranking was altered, there was only one change in the countries listed (Hungary replacing Norway) and the BRIC countries were in both lists (albeit in the bottom half). Re-analysing the data again, to adjust for the absolute number of studies carried out in each country since 2009, only brought relatively minor changes in the composition of the top 25 countries, with a slight shift from Western Europe to Eastern Europe and the BRIC countries remaining outside the top 10 (although with Korea jumping up to 4th). When I asked delegates to highlight any countries they had worked in that were not in this list, only a few suggestions were given, and these were mostly in the next 25 in the ranking model.

So, while 146 countries around the world have hosted at least one clinical trial, the “global” operations of many pharmaceutical companies may well be constrained to only 50 countries, or perhaps more like 35, where it is logistically practical, commercially viable and of regulatory relevance.

There is one fairly major caveat to this analysis: the data I used was at a study level, rather than considering the distribution of sites or even patients within a study. This would mask the impact of studies still conducted in the USA or Western Europe, but with a substantial shift in the proportion of patients recruited from Eastern Europe, Asia-Pacific and Latin America, which is widely considered to be the case.

So, globalisation is increasing, is here to stay, and is a good thing. But, for the moment at least, the pool of countries we are working in routinely is still relatively small. As we gain experience of working in a wider pool of countries, and investigational site teams in those countries gain more experience of working to global standards, these metrics will continue to shift… but possibly somewhat slower than we might expect.