From bench to bedside

Biopharmaceutical outsourcing provider Quintiles explains how managing product development has evolved in the age of Ebola

It can take anything from 15 to 20 years to steer a new medicine from discovery to general use and, even for therapies such as vaccines, the development programme can take up to 10 years. It is a long, arduous and expensive process, particularly when the patent clock is ticking and patients with unmet needs are pinning their hopes on a breakthrough.

Increasingly, too, clinical trials need to show not just that a product works effectively with an acceptable margin of safety, but can deliver sustainable value to hard-pressed healthcare systems.

The current Ebola outbreak has tested the traditional drug development process, and has required life science companies, non-profit organisations and government bodies to work together in new ways. Another significant challenge is identifying how to apply these lessons to combat not only other infectious diseases, but also additional diseases that cause a significant health burden.

Specific challenges
As a form of project management, drug development has much in common with equivalent functions in other industry sectors. The process is also highly specific, however. The degree of globalisation, risk, complexity and human involvement required to take a product from bench to bedside is a world away from building a dam or establishing a computer network.

Pharmaceutical project management is often virtual and 24/7, straddling time zones, national borders, ethnicities and cultures. “You may be dealing with a study involving 8,000 patients in over 40 countries, spread across 300 investigational sites,” comments Susie Boyce, senior director of project management at Quintiles. This calls for advanced people management and communication skills to be able to delegate to the appropriate level of local expertise, without compromising international standards of Good Clinical Practice.

Another distinguishing feature is the level of uncertainty involved. Attrition rates are such that only around 10 per cent of drug indications in Phase I safety trials make it as far as a new drug application to the United States’ Food and Drug Administration (FDA), or equivalent agencies elsewhere. 

Because no one can predict exactly how a new drug will behave in human beings, project management in this area also needs to be especially nimble and responsive to day-to-day changes. Many clinical-development programmes are designed to adjust to accommodate ongoing patient responses that will take the project in a new direction. In other cases, emerging evidence may indicate the project is simply not viable.

Drug development is also about engaging with an increasingly broad range of stakeholders, from scientists (both internal and external) to clinical-trial sites, regulators and policymakers, health-technology assessors, budget-holders in healthcare systems, patient advocacy groups and patients.

At the centre of all of this is the patient. Uniquely, patients are both the end user of a finished medicine and a crucial component of the development pathway, volunteering for participation in clinical trials. “Understanding and empathising with patient needs is therefore critical to pharmaceutical project management,” Boyce notes. “For project managers in the business, knowing that they are making a real difference to patients’ lives also gives extra impetus to career development and satisfaction.”

Despite the particular challenges of project management and a regulatory framework that prioritises safety, the early entry into development of a vaccine candidate for Ebola shows that these constraints do not preclude fresh thinking in drug development.

Lessons from Ebola
Speed is of the essence in this type of crisis. “Currently, there are no approved treatments or vaccines available to combat the Ebola virus,” notes Quintiles’ senior medical director Dr Prasad Velisetty MD. “Early supportive care with rehydration and symptomatic treatment improves survival,” he continues, yet the average Ebola case fatality rate (according to the World Health Organization) is around 50 per cent. That does not mean ignoring risk, but managing it differently. Moreover, the whole development effort has to be more intensive, agile, coordinated and creative.

There are precedents. As Jean-Marie Houle, vice-president of Phase I at Quintiles, observes, late identification of the H5N1 avian-influenza virus prompted a highly coordinated vaccine-development effort between companies and other stakeholders that were not used to working together. Addressing Ebola effectively will require a similarly focused collaborative push, in which industry, governments, non-governmental organisations and local communities must develop trust and transparency within a limited time frame. 

From a project management standpoint, these stakeholders are starting with a virtually blank slate. While the virus was first identified in the 1970s, previous efforts to address it were mostly confined to small companies with limited funding, or to academic laboratories. This presents a real challenge to companies conducting Phase I clinical trials. The few product candidates under consideration for development were mostly tested only on animals, some under less stringent laboratory conditions than is usual.

Meanwhile, the FDA and European Medicines Agency (EMA) are encouraging companies to apply for ‘orphan’ designation for their Ebola products, which would give them access to a range of incentives to stimulate development and facilitate placing on the market.

Fast but frugal
By any reckoning, this is a different type of project management, one demanding very quick results with relatively frugal means. As Houle notes, this is not the way the industry is used to working.

One reason for this is that tackling neglected diseases in markets with limited capacity to pay for treatment has tended to fall on governmental agencies and charitable bodies, such as the Bill & Melinda Gates Foundation. Yet, with its core markets reaching maturity, Big Pharma is showing more interest in the developing world and its endemic diseases.

Project management that is oriented to such diseases – with less cumbersome, more cost-efficient structures and a local research focus – may be instructive in helping the industry to achieve the diversification it sorely needs to offset pressures on costs and prices in its core markets. 
The challenge of Ebola, with an emphasis on speed of development backed up by robust ‘real-world’ and post-approval studies, also mirrors the emerging paradigm for medicines with high innovative potential that address genuine unmet need. 

Tackling these needs is also about creative collaboration. Creative collaboration is increasingly the model for all pharmaceutical research and development, since the industry realises that the roots of innovation often lie in universities, virtual biotechnology companies or public-private partnerships.

These new constellations present their own project management challenges, such as straddling commercial and academic mindsets or dividing up intellectual property. They reflect an environment characterised by public-health crises such as Ebola on the one hand and, on the other, by an industry trying to re-engineer its relationship with healthcare systems to provide long-term value without breaking budgets.

The Ebola outbreak is “like an alarm bell sounding”, Houle says. It is important to have properly coordinated research, informed by good project management practice, so that the rush for a viable vaccine or therapy does not end up delaying product approvals because of missed milestones.
Conversely, effective project management can help to ensure that healthcare systems and affected countries are not left critically exposed by the next outbreak of Ebola. It can also equip industry better for a future in which “fast and frugal” may no longer be reserved for emergencies.

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Quintiles is the world’s largest provider of outsourced biopharmaceutical development and commercial services