The ability to conduct high-quality clinical trials in emerging markets has improved “enormously” over the past 10 to 15 years, claims a new report for the US-based Association of Clinical Research Organizations (ACRO).

The report was commissioned from life sciences advisory and publishing company VOI Consulting, “against a backdrop of declining participation rates in the United States and recent criticism of international research by several academic journals”, ACRO notes.

While VOI Consulting acknowledges that “legitimate concerns” have been raised in the past about clinical trials in emerging countries, it found that ethical research norms “are global in nature and do not vary from place to place”.

Moreover, research sponsors have “very strong incentives to ensure that their investments in clinical research will be accepted by regulatory agencies in the developed countries where they earn the vast majority of their revenues”, the report says.

In fact, it points out, the regulatory and cultural conditions for clinical research in emerging markets are often more strict than in developed countries. The report cites the difficulty of conducting early-phase studies in India or placebo-controlled trials in Latin America.

“Patients in these countries may also seek greater input from friends and family before deciding to enrol in a trial,” VOI Consulting adds.

Necessary safeguard

It could be argued that tighter controls in these countries are a necessary safeguard against exploitation when poverty or low levels of literacy may encourage ill-considered participation in research.

However, the report for ACRO found that, while literacy rates in emerging markets for clinical trials were lower than in established countries, for the most part the disparities were less marked than expected. The unweighted average literacy rate for emerging trial locations was 93.4%, well above the world average of 82.0%; for established trial locations it was 99.0%.

There were some large disparities, such as India with a literacy rate of 61%, South Africa with 86.4% and Brazil with 88.6%. Even in India, though, the implications for informed consent were better than indicated by the statistics, “when one considers that clinical research is conducted primarily in urban areas and, per the 2001 Indian Census, literacy in urban areas is substantially higher (80.3%) than in rural areas (59.4%)”, VOI Consulting commented.

As for undue financial incentives, research norms dictate that any payments associated with a clinical trial should be examined as part of the ethical review process, while subjects in Phase II trials are “usually paid very low amounts”, the report notes – standard practice is to reimburse for meals, transportation and similar out-of-pocket expenses.

Healthy volunteers in Phase I trials may be paid substantially more but these studies are conducted “almost exclusively” in the developed world.

The report does acknowledge that even a modest payment may be “a considerable enticement” in very poor countries. All the same, “the argument over whether this constitutes undue influence ignores the fact that patients in the developed world are also subject to pressures that are extrinsic to the trial itself. In the United States, for example, 45.7 million people or 15.3% of the population did not have health insurance in 2007”.

Not for the likes of us

The report even questions the accusation that trials run in the developing world are largely for drugs to treat more profitable conditions prevalent in wealthier markets.

This “ignores the fact that, by definition, patients enrolled in a clinical trial suffer from the condition being studied”, it argues. “While cancer might not be a major cause of death within a country, individual patients are faced with a single cause of death and, if they have cancer, then that is the single cause of death they are most likely facing”.

Clinical research also plays an important role in improving the health systems and economies of emerging countries, VOI Consulting contends. In Poland, for example, 30% of cancer therapy in hospitals is funded by clinical trial sponsors.

These debates aside, the vast majority of clinical research is still conducted in countries with well-established infrastructures, the report observes. In 2007, for example, member companies of the Pharmaceutical Research and Manufacturers of America spent around 96% of their clinical-phase dollars in developed countries.

And a September 2008 report by Frost & Sullivan estimated that North America had a 49% share of global research and development, Western Europe 37%, the Asia Pacific region (which includes India and China) 13.5% and the rest of the world 0.5%.

Undoubted attractions

Nonetheless, emerging countries have their undoubted attractions. For one thing, VOI Consulting found that globalising trials could cut clinical development times in half, reducing overall development costs by nearly two-thirds.

This is a more important benefit than basic cost savings, the report argues. While costs per patient in India and China are estimated at one third of those in the US, when logistical and other factors are taken into account, the “fully loaded cost of conducting studies in developing countries often approaches levels that would be found in more established areas”.

Rather than putting up any more barriers to drug development, efforts in emerging countries should focus on enhancing the progress already made and continuing to train and monitor researchers, ensuring compliance with the highest standards, the report suggests.

“Restricting the ability of emerging countries to participate in clinical research would add still more expenses and further delay the ability of patients to access new therapies,” it states. “It would also deny an important source of investment, employment, healthcare and knowledge transfer to areas that are desperately in need of all these things”.