harmaceutical companies need to get to grips with late-phase clinical studies if they are to differentiate their products and build a comprehensive value proposition in an increasingly saturated and payer-dominated marketplace.

If they don’t take up this challenge, warns Dr John Hall, vice president global medical affairs, epidemiology and outcomes research for Quintiles Transnational, the payers themselves will be only too happy to step into the breach. And if that happens, “at the end it will come down to price”, Hall says.

He cites the recent news that US-based pharmacy benefit manager Medco Health Solutions was launching a head-to-head clinical trial of the blood thinners Plavix (clopidogrel, Bristol-Myers Squibb/Sanofi Aventis) and Effient (prasugrel, Eli Lilly/Daiichi Sankyo).

The aim of the Genotype-Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (GeCCO) study is to see whether a genetic subset of patients taking Plavix can achieve comparable outcomes to those on the new contender Effient (prasugrel, Eli Lilly/Daiichi Sankyo) – which is more effective overall but also more expensive.

As Hall points out, companies like Medco already have data from electronic medical records (EMRs) they can interrogate – albeit for “simplistic” outcomes. Since a payer’s overriding objective is to save money, “generics are always going to win” in these circumstances, he comments.

Life cycle management

“It’s all about life-cycle development,” Hall says. The concept of value has widened to encompass not just whether a drug is safe and “works” but other key factors such as how it performs against the current gold standard of care, cost-effectiveness, long-term risk management and satisfying reimbursement criteria.

While elements of value creation, such as patient-reported outcomes (PROs) or quality-of-life measures, can be incorporated into Phase II or III clinical trials, the “real goal” of these studies is getting the drug licensed, Hall observes. There is also a risk of over-egging the pudding. At this stage, “the more objectives you build in, the less likely you are to get anything”, he cautions.

Late-phase or post-marketing studies are concerned with what the product “actually looks like in real life”, rather than in the highly selective context of a mainstream clinical trial. For example, in a real-world setting patients may have several diseases and be taking several therapies at once, Hall notes.

To pursue late-phase development effectively, though, companies “need an ally”, he insists. Quintiles has its own expert group in the field, which is “expanding all the time”. Hall puts the company’s entire late-phase resource at around 800 staff worldwide.

Late-phase challenges

Their expertise in areas such as PROs, health economics, statistics and outcomes research can help companies tackle some of the particular challenges of late-phase development. The key, Hall told PharmaTimes, is that “you’ve really got to design your studies properly”.

That may involve addressing potential bias to compensate for lack of randomisation in a real-world population, or “non-interventional” data collection that does not involve clinical research associates actually visiting trial sites. There may not be much incentive for doctors to get involved, as they tend not to be paid much for late-phase work.

One way in, Hall explains, is to tap into existing patient databases connected to electronic medical records. To this end, Quintiles has hooked up with Cerner, a global supplier of healthcare solutions and electronic health record technology that sources data from patient registries in a number of different countries.

Another example of technology bridging clinical research and clinical care is Quintiles’ partnership with healthcare analytics specialist SDI for Risk Evaluation and Mitigation Strategies (REMS) mandated by the US Food and Drug Administration to ensure that real-world product benefits outweigh any potential risks.

As Hall points out, REMS or the equivalent Risk Management Plans in the European Union are “not necessarily the end of the world”. Besides fulfilling regulatory requirements, they can be used to collect post-approval data on (cost) effectiveness and value.

Nurses and patients can also help to fill out a drug’s profile post-approval. As Hall notes, “nurses and patients go together well”. Sponsored nurses not only play a crucial role in patient education and compliance with therapy, they can also collect outcomes data from hospital databases under contract.

Patients can contribute through media such as the iGuard online medical monitoring service, which was launched in 2007 with start-up funding from Quintiles. The service now has some two million users and is a “great way of doing” PROs, Hall comments.

Shift in emphasis

With the increased emphasis on late-phase studies to tighten up pharmacovigilance and optimise life-cycle management, there have been suggestions that the traditional stepping stones of Phase I to III trials will eventually resolve into a shorter, consolidated pre-approval process, with conditional approvals validated through emerging real-world data as the product settles into the marketplace.

For Hall, this would be “a very good model for the future”, although it is probably several years away. The seeds have been sown, though, not least through the swing towards personalised medicine. That means the product launch is only one stage in a continuum of value creation.

“You can’t just launch a product into the market and expect it to be a success anymore,” Hall comments.