Pfizer announced on December 5th that it was pulling the plug on torcetrapib, an investigational drug that raises “good” cholesterol and reduces plaque buildup in blood vessels that can cause heart attacks.
Pfizer had made an investment of nearly $1 billion on the development of torcetrapib. The investigational drug was three years into phase III clinical trials and had enrolled 15,000 patients. When more torcetrapib-related deaths than acceptable were identified by a Data Safety Monitoring Board after it had reviewed trial results, the 100 hospitals and medical clinics in three continents where the study was being conducted were notified to halt the study.
As India becomes increasingly preferred as a destination for the outsourcing of clinical trials, issues of informed consent and safety will become more significant. It is estimated that there are over 80 hospitals (government and privately owned) actively engaged in global and local clinical trials. Those numbers are expected to double or even triple each year by 2010, with 14,000 hospitals in the country...
In India, phases II, III, and IV clinical trials are similar to those conducted in other countries participating in multinational clinical trials. Unlike other countries, India historically has not allowed phase I trials to be initiated for new drugs. Phase I data must be available from other countries to initiate a phase II or III study.
If the experimental drug is discovered in India, then clinical trials may be conducted as human/clinical pharmacology trials with healthy human volunteers to determine maximum tolerated dosage in humans and adverse effects. However, more phase I studies have been initiated in India in the past 5 years by global pharmaceutical and biotech companies and CROs.
Some of the reasons why the government has not allowed phase I trials to be initiated in India is that it fears Indian patients may be treated like “guinea pigs” because of the need for regulatory policing that ensures protection of human subjects on clinical trials. The low literacy levels of many poor patients, potential volunteers, raises concerns of adequate informed consent about the clinical trials risks.
India is positioned to become the next major location for clinical trials. But as a nation it must be able to respond to the clinical trials infrastructure requirements, which include incorporating the international ethical principles and human subject protection issues, and incorporating the role of the institutional review boards (IRBs) that comply with the international community.
The United States has mandated since the Research Act of 1974 that all clinical trials be reviewed and approved by an IRB before a research study in humans begins, which means that any clinical trial that is reviewed and approved by the U.S. Food and Drug Administration (FDA) must be reviewed and approved by an IRB.
India’s emergence as the next clinical trials hub, as a result of an increase in clinical study outsourcing, must deal with these issues to be a viable location for global clinical trials. Some of the concerns will include the quality and nature of the IRBs that review clinical research protocols, ethical informed consent process/subject recruitment and availability of GCP-trained investigators and research teams.
A large patient pool with diseases and conditions found in the West and highly qualified physicians are essential, but India must overcome these barriers in order to fully capitalize on the emerging opportunities of clinical research because of the large financial investment by pharmaceutical companies.
Pfizer will not face the product liability lawsuits because patients in clinical trials must sign a waiver or informed consent form that indicates they understand the risks they face and accept that this is an unapproved experimental medicine evaluated through clinical research. Therefore, the informed consent process is important and must be a process of sharing information and not just a form that is signed once before the study begins.
Industry officials anticipate that the number of drugs will increase significantly in the next 5 to 10 years, and India is expected to benefit from that development. Even though clinical trials outsourcing to India relies heavily upon cost savings, quantity of physicians, available patients and IT strengths, the international community also requires clinical trials quality, compliance with ICH-GCP, ethical compliance, drug safety, risk management and government enforcement of clinical trials standards.
These requirements need to be addressed in order to meet global standards. Research indicates that by the end of 2006, the top ten major pharmaceutical companies will be investing $54 billion with 60% of those dollars to R&D and this investment is expected to increase to $65 billion dollars by 2008 and India could benefit from their investment.
One of the immediate changes that India can make is developing more IRBs that meet international standards and ensure patient safety. Also important is training more GCP-trained investigators, improving the informed consent process, and ensuring quality data at the investigator site level. The other changes may have to occur over time and with the involvement of the government, but there are many things that can be done at the local, physician, and hospital level.
Lisa Marie Castro, President, Sephmer Sciences Incorporated