Clinical Trials Arena: Explain some of the advantages and disadvantages of running trials in emerging markets
Jacquie Mardell: So the great advantage is access to patients with diseases sponsor companies want to study. Generally, those patients are much more willing and interested in clinical trials simply because their access to care is different to those found in Western Europe or the US. Additionally, patients are readily available, investigators are keen to collaborate, and prices are generally a lot cheaper when running trials in developing markets. So I think these are the three big advantages.
On the other hand, the disadvantages are the ethical considerations with enrolling patients in a trial for an experimental medicine where they may not receive any benefit. There are consent issues where the modalities of consent are different from the way it’s done in the West, where we rely heavily on individualised autonomy and the ability to read consents and so forth. There can also be very challenging regulatory pathways in numerous emerging markets, which are sometimes very long and laborious in that we can’t always tell what’s happening during the period of review. We have very few ways of being able to anticipate and respond to questions, time changes, and so forth. There are both strengths and weaknesses to the idea of using emerging markets.
CTA: From your professional viewpoint, are you seeing more companies, be it small, medium or big pharma outsourcing to emerging markets? Is it a growing trend?
JM: It has been a growing trend for the past decade, I would say. It has not grown to the extent we all thought 10 years ago, which I think has to do with the global financial recession. For instance, India used to figure prominently in that growth, but they’ve gone in the opposite direction and have shut down much of their clinical operations. So we haven’t seen the level of growth we originally anticipated, but we’re still seeing growth.
Nevertheless, as I speak with colleagues, more and more of them are comfortable with the idea of exploring, say, Eastern Europe or South America.
CTA: To that end, you said the growth has not been as quick as the industry anticipated – do you think some of that has to do with the regulatory barriers you alluded to?
JM: I think so. There may have been a naive expectation in the industry that when Western sponsors come to these countries that they would automatically roll out a red carpet and make it really easy. That hasn’t happened nor should it. Each country has a populace to protect, so it shouldn’t be easy. However, I think some of the barriers can be attributed to pathways that are still perhaps under improvement. There are greater concerns about the ethics and about what benefits can be obtained by, not only participants, but the physicians and healthcare infrastructure around them that I don’t think the sponsors have worked hard enough to work out.
CTA: How do you identify which regions are suited for certain trials when you consider patient populations, and so forth?
JM: There are a number of considerations we need to take into account. One is: Are we pursuing a registration strategy or an enrolment enhancement strategy? If we’re registering our product in the country in which we’re studying, the choices become somewhat easier. If we’re employing an enrolment enhancement strategy and we’re just going to find patients, we have to look at key factors like, diagnostic criteria.
For example, Western diabetes sufferers tend to be heavier than those in developing nations, which could make a difference in how the drug actually works. So we have to know things like that in advance before working out whether there are ethical considerations or placebo control considerations or reciprocity requirements, and figure out ways to manage them.
CTA: In your experience, having overseen studies in emerging markets, how do you ensure sites are running the trials properly?
JM: A lot has to do with the relationship sponsors have with CROs based in the countries as they’re the ones who can legally act within those regions. We (the sponsors) put a lot of responsibility on their shoulders to, not only manage our expectations, our timelines and our costs, but to meet all of the requirements of their regulatory setup, which we may not be terribly familiar with. So we really have to work in concert with those organisations. When I do that I spend a lot of time in the country, I spend a lot of time in the offices of the CRO getting to know the monitors, learning what their challenges are, going over what the needs of the study are, what the expectations of the sponsor are, and developing processes for that study to meet both sets of needs. So it really involves a lot of face time.
*Jacquie Mardell is the Senior Director of Clinical Operations at Ascendis Pharma