Exploring the inclusion of women, children and the elderly in clinical trials

Before a new medicine is licensed, or an established medicine is used for a new indication and can be marketed for the treatment of a human disease, it must undergo extensive safety, efficacy and formulation testing. Toxicity is first tested in animals, then in humans. Subsequently safety and efficacy is investigated in a series of clinical trials under strictly controlled conditions, first to determine whether the medication is tolerated by humans and then to assess if it actually can treat or stabilise the indicated condition. Finally, the results of these trials are reviewed by national medicine regulatory bodies to consider registration and licencing for use. In Australia, this body is the Therapeutic Goods Administration (TGA).
Aim
The aim of this study was to investigate whether the participation in clinical trials for drug discovery in Australia and New Zealand provides a true representation of the intended populations in which the medication is likely to be used.
Methods
This project was preliminary in nature, and designed as a descriptive research study to evaluate the complex issue concerning inclusion of all population groups in clinical trials and mitigation of the associated risk, rather than exclusion to avoid the consequences of the risk. Evaluation (audit) of research can be used to analyse a system, program or the performance of an organisation. Here, it was used to analyse the data from the Australia and New Zealand Clinical Trial registry (ANZCTR) to better understand the level of participation of the target populations and compare that to the literature. The study hypothesised that there is an intentional under-representation of the elderly, women and children caused by excluding them during recruitments for clinical trials. It also tested the assumption that the information in the ANZCTR database, public access, would be sufficient to confirm or deny the study hypothesis. The study was conducted through three phases: a literature review, analysis of the ANZCTR public data between 2009 and 2013 and a public-opinion survey. The survey aimed to establish whether the finding from the literature and the ANZCTR data analysis provides a true reflection of the study population feedback.
Results
The literature indicated that there is a significant under-representation of women, the elderly and children who are more likely to be intentionally excluded from participation. The ANZCTR records presented challenges, as only four out of 3000 studies had been updated after the end date to include the number of participants who had actually been enrolled. Additionally, reasons for withdrawal from participation were not recorded. There were no significant under-representations of women, the elderly or children found in those four trials.
Finally, out of the 103 participants in the survey, 27.8% of women, 45.5% of the elderly and 17.6% of parents strongly agreed to participate in a clinical trial without having the disease; and 30.6% of women, 33.3% of the elderly and 20.6% of parents agreed to participate even if they were happy with their current treatment. Furthermore, 66.7% of women, 42.4% of the elderly and 35.3% of parents strongly agreed that they would participate if they were not happy with their current treatment. Similarly, 77.8% of women, 51.5% of the elderly and 67.6% of parents strongly agreed to participate if the treatment was their last hope for a cure. Additionally, 58.3% of women, 39.4% of the elderly and 41.2% of parents strongly agreed to participate in a clinical trial if they had the disease the new medicine was treating, and they were offered lifelong health insurance which covered any side-effect or damage caused by the tested medicine, whether or not there was another treatment currently working. In comparison, 55.5% of women, 33.3% of the elderly and 47.1% of parents strongly agreed to participate to do the same, but only if there was no other treatment working for them. Finally, 44.5% of women, 18.2% of elders and 64.7% of parents strongly agreed to participate in a clinical trial if they had the disease the new medicine was treating for a payment, regardless of if there was or there was no other treatment working; while 47.2% of women, 45.5% of the elderly and 52.9% of parents strongly agreed to do the same, but only if there were no other treatments working.
Discussion
There was an assumption that the confidential ANZCTR system captured complete data on current clinical trials; however, the data available through the public portal was clearly suboptimal both for the researchers and the public. This study was questioning apparent under-representation of the elderly, women, and children in clinical trials and the reasons for the level of representation. One possible explanation was thought to be a lack of intention by researchers and the industry to include those groups. However, the study concluded that there was insufficient evidence to confirm this explanation and suggested that the problem might be multifactorial. Some under-representation might be due to the exclusion criteria in some studies as required due to specialisation or high risk; however, it appeared that there was a significant element related to participants’ personal choices.
Conclusion
A better insurance cover system is required to assure participants that any damage to their health which might occur during the clinical trials would not cause them financial burden, and that the researchers would take all possible risk mitigation measures before conducting such trials. Broader communication through the provision of accessible historical data would improve confidence in those invited to participate, that their rights would be protected and they would benefit from their participation-both at an individual and a societal level. Improving the awareness of benefits and risks experienced by the previous participants would provide the public with a better understanding of clinical trials.