Current challenges in conducting clinical trials
Comparing apples and oranges
International Clinical Trials Day, held on the 20 May 2021, marks the anniversary of one of the first clinical trials. In 1747, James Lind, a doctor onboard the HMS Salisbury, investigated the causes and treatments of scurvy. Lind’s trial involved twelve sailors with scurvy. He assigned two sailors to each of six different dietary regimens for a period of 14 days. Lind observed that symptoms of scurvy dramatically improved in the group who ate oranges and lemons compared with those who received the other dietary regimens. By ‘comparing like with like’, Lind pioneered the methodology for investigating different treatment arms in clinical trials. Clinical trials continue to be a major driving force in medical innovation and improvements in patient care. However, there are still many challenges to overcome in the successful inception and implementation of clinical trials.
A question of prioritisation
Firstly, one must choose the research question. Clinical research involves cross-functional collaboration between research sponsors, investigators, patients, payers, clinicians and regulatory authorities, all of whom may have different incentives for developing a specific research question based on their own interests. For instance, an industry-sponsored trial may be geared towards obtaining regulatory approval for a new medicine. With this motivating factor in mind, industry-sponsored research questions may be built around a simple comparison of two therapies in a highly selected patient population. By comparison, an independent investigator may have limited scope for selecting a research question due to financial constraints and obligations, and so to receive financial study support, the priority may be to convince the funding body that not only is their research feasible, but also that they might get a successful outcome. Funding bodies may prioritise what they consider a ‘safe-bet’ over more risky and innovative research.
Investigating: the issues
Clinical trial investigators are the key individuals responsible for ensuring that a study is carried out according to the protocol so that specific research questions can be answered. However, the clinical trial investigator workforce is shrinking. A recent study in the USA revealed that the number of investigators signing up to participate in new trials declined by approximately one-third from 1999–2015. Furthermore, the ‘one-and-done’ phenomenon is becoming increasingly prevalent, with more and more investigators leaving clinical trials altogether after conducting just one drug trial. The high turnover rates can contribute to inefficiency, instability and increased costs for the clinical research organisations.
It is not clear why there is such a high turnover of clinical trial investigators, although it may be related to being overburdened by large amounts of work. To conduct a trial, an investigator must first overcome many barriers, such as obtaining institutional review board (IRB) approval for the study. This can be a lengthy process, with investigators often having to respond to multiple review requests. Not only are regulations country-specific, but different IRBs can vary considerably in how they interpret country-specific regulations. Such inconsistencies in IRB recommendations can complicate the process of initiating large multicentre clinical trials because multiple IRB approvals are required.
Patient recruitment can also be challenging for clinical trial investigators. Informed consent is an ethical and legal requirement for research involving human participants – before agreeing to enrol in a clinical trial – each patient must be made fully aware of the purpose, benefits and risks of the study. Obtaining informed consent from each subject in a clinical trial requires a significant amount of time from both patients and investigators, during which the investigator needs to discuss the overall process with each patient, develop accessible consent documents, obtain patient signatures, and keep a log of all the paperwork received. During a workshop on the current challenges around informed consent, it was argued that an extensive consent process may burden researchers and slow patient recruitment.
It has also been suggested that language barriers may be an issue that hampers some patients in providing informed consent. One study reported that many patients sign the consent form without fully understanding the benefits or risks of the study; and misunderstandings about the trial can lead to lower patient retention rates. Therefore, it is vital that study investigators adopt accessible language during the informed consent process. This is particularly important for patients who may not be interacting with the study team in their first language, and it is worth considering translations or provision of interpreters where appropriate.
Patients from racial and ethnic minorities also face barriers to clinical trial participation. In 2011, the US Food and Drug Administration reported that only 5% of clinical trial participants were African American despite them representing 15% of the total US population. This underrepresentation of racial and ethnic minorities in clinical studies can reduce the relevance of the results and also highlights inequalities around healthcare provision. The importance of diversity in clinical trials was explored in our blog on the 17th Annual Meeting of the International Society for Medical Publication Professionals. We know that it is a complex multifaceted issue, stemming largely from mistrust and misinformation, and so there is a clear need for more proactive engagement with these communities to help in educating them about clinical trials in a transparent and honest way.
Although there are still many barriers to overcome, since their inception in 1747, clinical trials continue to be a key research tool for evaluating the safety and efficacy of new medicines and medical products. We would like to take the time to thank patients, investigators and all those involved with clinical trials for their vital contributions in advancing medical information and patient care. Bioscript are proud to be involved by developing high-quality clinical trial documents, such as protocols and study reports, and supporting our clients to improve patient engagement, recruitment and retention. To hear more about our integrated services, please contact us at firstname.lastname@example.org.