Clinical trials conducted in developing countries are on the rise. There are numerous good reasons for this, apart from the always cited cost saving. Especially the willingness of patients to participate in clinical trials is high and the same is true for the motivation of physicians to conduct them. However, there are special risks linked to clinical trials in emerging economies, but they can be managed as long as the sponsors are duly aware of them.
Data obtained from clinical trials performed in emerging countries
An increasing number of clinical trials are conducted in countries with emerging economies. A central driver behind this trend is the need for certain trials to be conducted on patients who have never before received any treatment for the disease under investigation. Such patients can be more easily found in developing countries where healthcare is less freely available.
Particular data integrity issues arise around clinical trials conducted in emerging countries. Most clinical trials require their patients to be 18 years old or more. However, in many emerging countries there are no official registers of births, and potential patients may not have birth certificates or other forms of ID such as passports. It may be difficult, if not impossible, to accurately verify the age of a patient. It is therefore crucial that if an investigator is in any doubt about whether a patient is at least 18, that patient should not be included in the trial. This is important both to avoid jeopardizing the reliability of the trial data and to safeguard the rights of the patient. Clinical trial monitors and auditors must also thoroughly check whether the patients enrolled into the clinical trial are actually real people, both by checking identification documents and by looking at the records of the patients’ medical histories.
Concerns about conducting clinical trials in countries with emerging economies
There have been some publicly voiced accusations that the life sciences industry has been relocating clinical trials activity to countries with emerging economies because they have less stringent laws, fewer controls and lower costs. Costs are of course an issue, but a clinical trial conducted in an emerging economy must comply with exactly the same principles of good clinical practice (GCP) as a clinical trial in the European Union (EU), the UK, Switzerland or the U.S. Clinical trials must also adhere to the same standards of auditing regardless of where they are conducted. Regulatory authorities in the EU, Switzerland, the UK and the U.S. could refuse the marketing authorization of a medicinal product if it appeared that the data submitted in support of the application for marketing authorization stem from clinical trials conducted in violation of the GCP principles.
There are in fact very good reasons why sponsors of clinical trials may choose to conduct a clinical trial in a country with an emerging economy, reasons that have nothing to do with cost. These mostly center around the fact that certain patient populations can be more easily found in such countries, as discussed above. Neither is it true that clinical trials in emerging economies are conducted to lower standards. In clinical trial sites in countries with emerging economies, the investigators are often extremely strongly motivated and demonstrate very high scientific, therapeutic and ethical standards.
Risks arising from clinical trials conducted in emerging economies
There are, however, areas that ought to properly be of concern when conducting a clinical trial in a developing country. It is important to be vigilant around the oversight risks that may arise when the conduct of a clinical trial is outsourced to a contract research organization (CRO) based in a country with an emerging economy. For some years, pharmaceutical companies have been outsourcing most of their clinical studies activities to CROs. However, many of the well-known CROs in the industrialized world do not have offices in emerging markets and must themselves hire local CROs. In such a scenario, the local CRO is not directly responsible to the sponsor, but rather to the main CRO. Most sponsor-CRO contracts do not contain a clause that allows the sponsor to monitor a sub-CRO. However, proper oversight can be achieved if sponsors use a multidisciplinary legal team with a strong experience in the clinical trials field to provide support and mitigate risks relating to sub-CROs and to advise on the setting up of adequate contractual arrangements.
There are also very significant risks arising from the vulnerability of patients. Patient populations in developing countries are often illiterate. It is also common for them to have a very different relationship with doctors than is typical among patients in developed world, one characterized by greater dependency. For example, patients in developing countries often do not dare to question a doctor’s suggestion that they participate in a clinical trial. These circumstances give rise to issues regarding informed consent. Informed consent is, in itself, a Western concept, but it is a pivotal condition for a clinical trial to be valid.
Bribery and corruption charges leveled at the sponsor are also a risk. Clinical trials usually involve the transfer of large amounts of money, to for pay investigators’ fees, sites and the expenses of trial patients. Developing countries may have lower living standards and fewer economic resources, and bribery and corruption may be more widely accepted as a normal part of doing business. In such countries, there is an increased risk that local intermediaries, such as local CROs, use the sponsor’s funds and the context of a clinical trial to obtain, or maintain, business from government authorities. Therefore, funding, fee payments and other money transfers related to trials in such countries must be monitored very closely. Particular attention should be paid to this point when setting up a CRO oversight plan.