Pharmaceuticals on trial

Regulation needs to catch up with practice as the pharma industry increases testing in emerging economies.

Pharmaceuticals thrive on their R&D departments. But it also costs a fortune to run these lucrative departments and the current economic climate has not made things any easier for pharma companies. To maintain margins and minimise costs, some are trying to shift R&D operations to cheaper emerging markets. But the ethics and regulations are complex, particularly when it comes to clinical trials.

According to Outsourcing Pharma, clinical trials account for two-thirds of the development costs for new drugs. Historically clinical trials have been conducted in Western countries, with the US taking the lead, followed closely by Germany. But the average trial participant pockets US$2,000, quite apart from the staffing costs. In an increasingly expensive world, pharma companies are keen to reduce these costs.

Hence the growing use of off-shoring. In 2005, almost half of the 1200 clinical trials conducted by the 12 largest US pharma firms included an offshore location, with China and India among the favourite destinations. According to management consultancy firm AT Kearney, China is a particularly attractive location for tests, with the cost of a trial just half that in the US (see chart below).

In Russia, where the hospital system treats all patients with similar symptoms on the same ward, patients can be recruited up to 10 times faster than in the US. Other Eastern European countries such as Bulgaria, Ukraine and Romania are also increasingly attracting clinical trials, thanks to high educational attainment and low relocation rates. Regulations, infrastructure and staff expertise are also important.

There is no doubt that when clinical trials are successful, both sides stand to benefit. Pharma companies get to reduce their costs, while patients in emerging markets gain access to cutting edge research. But what happens when it goes horribly wrong? As pharma companies move into poor countries, where trial participants may be less well-educated and more desperate, the need to protect human guinea pigs becomes ever more urgent.
Pfizer under fire

The recently concluded Kano-Pfizer case shows what happens when trials go wrong and the safeguards are inadequate. In this notorious case, over a trial conducted in 1996, 11 young children died and 189 were left severely deformed after Pfizer prescribed the drug Trovafloxacin (commercially known as Trovan) to cure an outbreak of meningococcal meningitis in the Nigerian state of Kano.

Kano state subsequently filed civil and criminal suits against Pfizer demanding US$2.75bn in compensation for what it believed was an illegal drug trial. Pfizer fought back – for 13 years – saying that the tests were conducted with the full corporation of the Nigerian government and saved hundreds of lives. The survival rate for those tested was 94.4% in an outbreak that overall cost 12,000 lives, argued the company, before finally agreeing to settle the claims for US$75m.
Pfizer also says that the clinical study at Kano met all international standards governing the conduct of clinical studies. The World Health Organisation (WHO) guidelines for good clinical practice apply for each and every country, while the Helsinki convention on Human Rights also serves as a legal framework that aims to protect the life of the human subject participating in the clinical trial so that ‘… no one shall be subjected without his free consent to medical or scientific experimentation’.

In the Pfizer trial, the participants consented, signing papers written in the local language, and participation was voluntary. But there is some dispute over whether the participants understood the risks. Pfizer claims that before the Kano trial, Trovan had been tested on at least 5,000 Americans with no notable side-effects. But it is not clear if any children were involved in those studies.

Risks are inevitable in any trial. Without them, new treatments would remain trapped in laboratories. But the Kano did raise the question of whether international standards for clinical trials are enforced as stringently in developing countries, where the regulatory framework as well as participants' awareness may be weaker. In India, audits of clinical trials have brought out glaring irregularities suggesting that sponsors and Contract Research Organisations (CROs) are not following the rules. The Drug Controller General of India has now made registration of CROs mandatory as of June 2009, and is moving to impose stricter controls over the country's 290 medical colleges.

The world of pharma is cut-throat, and getting more so. But unlike any other product development, drug development ultimately involves a human in its manufacturing process, so strict guidelines and strict enforcement is vital. The land-mark Kano case should make that clearer than ever.