History of abuse of clinical trial subjects (participants) is long and regrettable. The earliest known cases of these abuses date back to the Second World War when the Nazis conducted a series of experiments on war prisoners without seeking their consent. These prisoners were forced to participate in these experiments and were subjected to extreme torture, pain, and even death.
Such clinical trial subjects are called vulnerable subjects when their ability to protect themselves is either considerably reduced or absent. These subjects have recognizable increased chances of suffering additional or enhanced damage.
Who can be considered as vulnerable subjects?
The vulnerable subjects may include children, pregnant women due to additional risk to their foetuses, prisoners, women of childbearing potential, and patients with psychiatric disorders. Certain subjects may be forced to participate in the clinical trials using influence or threat. The poor subjects may be lured to participate in the clinical trials by offering monetary or other benefits.
According to Central Drugs Standard Control Organization (CDSCO), the national regulatory body for Indian pharmaceuticals and medical devices, subjects with incurable diseases, in nursing homes, in detention, unemployed or impoverished, in emergency rooms, homeless persons, nomads, refugees, and any ethnic or racial minority groups also fall into the category of vulnerable subjects.
How and why are the subjects exploited?
The subjects may be coerced or lured into participating in certain clinical trial which may ultimately harm them. They may not be provided with adequate information about the clinical trial procedures before taking their consent for participation. Such tactics are generally employed due to the following reasons:
- The sponsors of clinical trials aim to complete the recruitment of participants as quickly as possible to lower the overall cost
- The clinical trial investigators have economic interest in the recruitment of more subjects
- Ethics committee is not working efficiently to protect the rights of the volunteers
- Lack of effective regulations in place or due to oversight by regulatory bodies
Who are the stakeholders involved in the protection of vulnerable subjects?
The major stakeholders include:
- Regulatory Bodies – Clinical trials in different geographical locations are regulated by regional regulatory authorities. In India, Drug Controller General of India (DCGI) is responsible for regulating the conduct of clinical trials.
- Ethics Committees (ECs) – These are responsible for ethical conduct of the clinical trial and safeguard the rights, safety and well-being of all clinical trial subjects.
- Investigators – Subject matter expert, usually doctors, who are involved in the conduct of the clinical trial procedures on the clinical trial subjects. They are responsible for conduct of the clinical trials.
- Sponsors – Sponsors conduct clinical trials to find out answer to their research question. Sponsors take approval from the concerned regulatory authorities for the conduct of clinical trials and arrange funds for conducting clinical trials.
- Subjects – Volunteers who participate in the clinical trials.
How to protect vulnerable subjects?
Currently due to different factors, there is no uniformity in the understanding and the grading of risks for vulnerable subjects globally. The following steps can go a long way in protecting vulnerable subjects:
- Regulatory agencies of different nations can come together to frame comprehensive and harmonised regulatory policies to protect vulnerable subjects.
- A very high-quality consent process is required to ensure that all the aspects of the clinical trial have been explained by the investigators and understood by the subjects before agreeing to participate.
- The informed consent document (ICD) should comply with all the requirements of the local regulations.
- The language of the ICD needs to be non-technical and easily to understand for a minimally literate subject.
- The ICD should not be too long and preferably have a section of “frequently asked questions” at the end.
How Vulnerable Subjects are Protected in India?
In India, CDSCO has outlined the following special provisions for the protection of vulnerable subjects:
- Volunteers selected for a clinical trial should ensure equal distribution of burden and benefits among all the communities of the society.
- Research on the economically weak subjects should not be conducted to benefit financially affluent population.
- Rights of mentally disabled subjects, incapable of giving informed consent, should be adequately protected.
- Inclusion of vulnerable subjects such as students, prisoners, subordinates, employees, and service personnel should be adequately justified.
An audio-visual recording of the consent process has been made mandatory if the participating clinical trial subjects are being included from vulnerable population.