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The Biggest Challenges in Conducting Global Clinical Trials


  • August 6, 2014

  • The Biggest Challenges in Conducting Global Clinical Trials
    By Chris Gallen

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    Trials have to test the hypothesis that the treatment differs from placebo or another treatment. To do that you have to compare results from the groups. The key to your ability to do so is the variance between the groups. If you have two means that have a decent separation and the variation around each mean is narrow, they will separate with good power. However, if the variation is broad and umbrella-like regardless of how different the means are, you will not be able to separate them with a do-able number of samples. So the key in trials is to minimize variation. Each nation is a complex source of variation for a number of reasons, including, but not limited to, different standards of care in the countries, different ways of interpreting the same medical terms and definitions in each country, different availability and use of concomitant meds in each country, and in some cases, different genetic make-up among different ethnicities in each country. The more countries, the more variation, the less power of the trial. You risk the trap of going to a lot of countries because you need the enrollment, but by stretching out the variation, you actually need yet more people to have the power to see a result. Some of these factors can be dealt with by careful training, emphasizing how terms are to be interpreted in this study, having a central reviewing authority when needed to check that the same criteria are being met etc. Some factors – for example, differences in metabolism by ethnicity, can be estimated with reasonable facility by understanding the mechanisms pertinent to the treatment and knowing whether there is a known significant aberration in that mechanism in a country you are considering. The bottom line is that hope is not a strategy, asking someone’s opinion is not a strategy, actually thinking through the pertinent factors and getting the science right is the basis for a discerning strategy. 

    Differences in global regulatory systems are another source of headaches and delays. In general there are two broad categories of countries. The first are the ICH-countries which in general follow a fairly similar process, albeit with individualizations in the paperwork and types of questions you get from country to country. The second are the non-ICH countries like China and India with a different approach, strategy and process and different assumptions about process who typically have very serial processes and take much longer to get started but because of large populations once going can enroll at a good rate. Having conducted trials across a wide range of therapeutic areas, products and countries, I tend to reject simplistic assumptions about one country being better or worse than another. Obviously the starting point is the disease to be tested, the measurements to be used, the level of technical difficulty in making the right diagnoses and measurements, and the level of medical skill in the countries in question. From there, I tend to look at my experience from the following lens – in studies where we were testing a drug we knew worked, for example an approved therapeutic against placebo, were the countries able to separate effective treatment from placebo? This outcome is a mixture of many factors, but from a Pharma perspective, if a lab or a country reproducibly cannot separate known effective treatments from placebo as a general rule, I would certainly not want them testing a new drug against placebo.

    Hear more at the 5th Annual Executing Global Clinical Trials conference on September 10, 2014 in Boston, MA. To register, visit: http://theconferenceforum.org/events/global-clinical-trials/