ACRO’s Doug Peddicord addresses key issues	June 2009

Doug Peddicord, Ph.D., executive director with the Association of Clinical Research Organizations, spoke with R&D Directions Managing Editor Michael Christel about several key issues facing CROs and pharmaceutical companies, including comparative effectiveness research and globalization.

Q: What are the main issues in the industry right now that ACRO and its members are directly impacted by or are keeping a close eye on?

A: I think we and customers in pharma both are looking a lot at the issues related to comparative effectiveness. One big issue is comparative effectiveness research and what that's going to mean for healthcare reform at large, but then what it means for drug development, R&D funding, etc., over time.

Another big issue that we're following is HIT, health information technology, which, similarly, is kind of an issue of how that plays within the context of healthcare reform, as well as all of the clinical research industry may be impacted by various kinds of new regs relating to HIT.

Next one for us is really the globalization of research; that's something that we've obviously been involved with for a long time. The question is how that's understood, how it continues to evolve, and whether or not there will be countervailing kinds of forces at some point that may diminish the amount of international research.

Lastly, we've worked with the office of Rep. Diana DeGette (D-Colo.) for a number of Congresses. She's been trying to develop a bill that would help to resolve some of the differences between FDA regulations and common rule regulations when it comes to research. We think that's a worthy goal.

Q: How would you assess the state of late-stage drug development these days?

A: Late phase continues to do well for a variety of reasons. Some of them are the things that are going to work their way into comparative effectiveness research really are late phase. In addition, the FDA's implementation of the REMS (risk evaluation and mitigation strategy) requirements will make for more in the way of late phase. So not only will you have government doing comparative effectiveness, but payers are increasingly doing something that looks rather like comparative effectiveness.

Again, the REMS and the rest of the sort of post-approval drug safety issues probably means that late phase actually continues to very strongly positioned. I think it will also mean that companies will have – as many of our members do – the capabilities to do what I would see as sort of related research, like health outcomes research, like health services research. Another words, now we've moved beyond simply the clinical trial paradigm, but we're really into data analysis and large data sets and those kids of things. Most of the large global CROs do have those capacities.

Q: Has the relationship between sponsors and CROs evolved to the point where CROs are now regarded more as collaborative partners in the process, rather than strictly vendors?

A: The goals of our industry for a long time has been to be not only a provider of services and infrastructure, but increasingly to be a partner that's kind of embedded into the process. We've certainly seen a lot more of that over the last year or so. You've had three our four really big deals, the Lilly-Covance partnership, Quintiles has a similar partnership. The reality is as pharma begins to restructure to be focused more on core competencies, then that really does leave room for a lot of the development expertise to exist within the CRO side of the equation.

They'll be in some ways both closer relationships and, hopefully, sort of more permeable kinds of boundaries between the two so that there's more of a shared infrastructure. It's the model of R&D – pharma is great at the "R" side and the development side has changed a lot in the last 25 years. There's much more opportunity for pharma to have partners to do the development side.

Q: The new administration has said comparative effectiveness research will play a big role in the new healthcare model. How do you assess the comparative effectiveness debate?

A: On the whole, it's a good thing. It's actually an idea whose time has come, in any case. With that said, what everybody wants is for comparative effectiveness research to fuel evidence-based medicine so that medicine is actually based on good evidence and to fuel a kind of wealth of information to be available to docs and patients at the point of care. That's what you want. You want comparative effectiveness research that underlies lots of information at the point of care and a delivery of evidence-based medicines. Those are the goals.

What people get concerned about is you can have comparative effectiveness research sort of drive in towards those two goals, but you can also have it drive toward the goal of mostly cost controls. Ultimately, if it's you as a payer, then it may well be aimed at controlling costs, controlling of the availability on a formulary, etc.

One of the issues that everybody should have with that is it's not as simple as just saying that there shouldn't be efforts to control the cost of medical care. Because actually we're quite aware that ultimately, there has to be efforts to control the cost of medical care. But, at this point in time, the analyses that are available for this data aren't very sophisticated; you tend to end up with, ‘We think drug ‘A’ and drug ‘B’ or drug ‘A’ and treatment ‘B’ are roughly equivalent.’ But the roughly equivalent is the hard part. Do we talk about quality of life equivalent? Do we talk about quality-adjusted life years?

There's a pretty reasonable way to outline a paradigm that says if you do comparative effectiveness research, I want you to try to aim for evidence-based medicine with lots of information for patients. I think we're less good right now at being to make judgments you as patients ought to be able to make. Most patients make judgments every day on the question of branded pharmaceuticals versus generics; today generics account for about 70% of prescriptions. It's entirely reasonable for you as an individual to have enough information available about effectiveness and about cost to make some decisions. That makes perfect sense.

The concern is that payers won't be quite as nuanced in that thinking. You may well say with two equivalent treatments, this one is a lot more comfortable, this one I like better. You might even say that today for treatment ‘A’ you have a $10 co-payment, for treatment ‘B’ you have a $30 co-pay, but you can make that pick. The worry is that if you're the payer, then you always make the $20 whatever it is.

Q: How might comparative effectiveness research for marketed products affect efforts in R&D?

A: There's already higher standards. What may have a lot of impact, not so much on the drug side, but the potential it has on the procedure side. A lot of what drives healthcare costs are things like medical procedures. Today, you as a neurosurgeon, if you think about developing a new procedure, a new and better way to do ‘X’, you are unlikely to think a lot about the issue of costs involved, and to think about the issue of whether or not it will be comparably effective or more so/less so in relation to some procedure. You may be looking for a way that's more effective in the sense that it's easier for the surgeon to do or has fewer side effects or something. But you're probably not thinking very much about the impact of cost in that. It certainly has the potential to impact innovation even outside of pure drug development stuff.

Q: With the continued emergence of clinical research in developing markets, how crucial is it now for CROs to have significant global capacity?

A: I would say in starting, patient recruitment really is a huge aspect of globalization. In  fact, if you look at most emerging markets, often people say there are all these cost advantages. The truth of the matter is, at least as I read it, most of those cost advantages diminish pretty quickly. As a market becomes a little more mature, as there's a better medical infrastructure and better regulatory infrastructure, most of those cost advantages diminish fairly rapidly. It's not like going to an emerging market gets you all kinds of cost advantages. It may, but for a fairly brief time.

What really gets you going – looking at the figures, in the United States it's something around 3% of cancer patients participate in clinical trials. The notion is that if you had 5%, then what you would do is cut development time by five years, by six years, etc. If what you were to look at is the reason to be in a global market is because the opportunity to access or to offer involvement in a clinical trial to a cancer patient, to a population of 30,000 cancer patients U.S. or 200,000 cancer patients if you add two more countries, simply is compelling.

In terms of globalization, the numbers are pretty compelling. Beyond that, the cost advantages in many ways have more to do with speed than they do with cost. If what you can do is access many more patients and get through your trials faster, what you end up with – and even if it costs you the same on a per-patient basis – is if you can get done in two years instead of four in terms of the R&D dollars, than you've saved a lot. It's patients first, it's time second.

Now, clearly there are always challenges. People worry a lot about ethics, about informed consent, and about, in many ways, immature regulatory structures. The FDA, even if I think it's under-resourced, is massively resourced in comparison to many other drug agencies – China, India. CROs, for instance, can deal a lot with the quality issues. The reason that a CRO can indeed go into a variety of countries is because they're very well-versed in GCPs, they're very well-versed in initiating sites, in training site personnel and investigators to GCP standards.

The advantage of globalization they (CROs) offer is the opportunity to offer consistent quality around the world. That's a huge advantage. The bigger concern in many ways is just the notion of whether or not the regulatory infrastructure, the drug agency, is going to have good enough skills to make your investment in a given country really well.

Q: You mentioned the ethical concerns of globalization. How do you respond to reports like the one earlier this year in the New England Journal of Medicine that question the ethics and science of American companies increasingly conducting clinical trials in developing countries?

A: The New England Journal article raised three or four important issues, including informed consent and the like. Those are important issues and as we noted in our response (ACRO issued a statement on Feb. 20), we think that deserves a real conversation between pharmas, CROs, academic organizations, etc. That said, I actually think academic organizations – the authors of that article– are going to have greater concerns about their ability to do research overseas, because they really lack the resources to do research overseas.

Let me put it this way: if NIH is to fund a study of a drug that's going to address typhoid [fever] or something that's more likely to be outside of the U.S., if the NIH funds that study and provides the primary funding to an academic organization, an academic institution, the truth of the matter is that if you need to do your research in Singapore or Thailand or China or the like, that what that academic organization may do, perhaps should do, is in fact then work with a company like a global CRO that actually is already experienced in running trials in Thailand or Singapore or China or wherever. As opposed to if you happen to be the investigator at academic institution ‘A,’ the notion that you got to go open a new site with maybe a colleague academic organization in Singapore. That's pretty daunting. The truth of the matter is our industry has spent a lot of time and a lot of money in developing experience and infrastructure outside of U.S.

Q: But what about the purely ethical concerns of doing research overseas?

A: The ethical concerns certainly have been highlighted for a long time, every since the National Bioethics Advisory Commission, etc. Those are not new. There are apparently also just some plain old financial concerns, which is that some people say, 'Gee, if ‘x’ percent of research occurred in the U.S. 10 years ago and now it looks to be ‘x’ minus 10, that worries me.' For all the reasons I've given – access to patients, growing infrastructure, etc. – I'm less concerned about if we can say that the quality is the same. Is there any good reason for us to say that if it was 60[%] and now it's 50, is that a bad thing? I don't see it as a bad thing, but if I operated only in the U.S., I might see it as a bad thing.

We (CROs) are very versed in international standards. If you can get the research done, the data out faster with access to more patients, and you can guarantee quality, that I think is the issue.