Overcoming the Barriers to Clinical Trial Enrollment in Cancer Research

Cancer research continues to face a significant challenge with patient enrollment. The advancement of cancer prevention, diagnostics and therapeutics is severely hindered by poor patient recruitment numbers. With the data showing only a mild improvement over the last decade, more research is needed to understand the barriers to patient enrollment for cancer clinical trials and potential solutions to address this overwhelming issue. 

Introduction

Enrollment of patients in oncology clinical trials remains a problem for cancer research, improving marginally over the years. The rate of trial participation over several decades ranges from 2% to the more recent 8%. Despite cancer patients demonstrating an eagerness to participate, the actual enrollment statistics are conflicting and suggest a number of barriers are in place which must urgently be addressed. 

The participation of cancer patients in clinical trials is fundamental to the advancement of new treatment to improve the outcome for all patients. Clinical trials offer the chance for patients to access the newest treatment available.

Without enough participants, clinical trials are often terminated, as the number of patients is not sufficient to represent the population which is essential to measure the efficacy and safety of drugs which can vary between individuals. Preclinical studies are an important part of drug development; however clinical trials are arguably more so as they assess drug pharmacokinetics within the human body in order to assess risk vs benefit. 

It is of paramount importance that research continues to investigate the barriers to enrollment which hinder areas of cancer research. The impact of this can result in a negative outcome for patients in whom current treatment is ineffective or demonstrate a significant resistance to. 

Current barriers

Uncertainty about risk

The fear of potential side effects and impact on daily life is one of the greatest deterrents for clinical trial enrollment and often arises as a result of misunderstanding or false information. This emotional barrier can arise for a number of reasons, one being a residual mistrust of medical science from unethical, dated clinical research or often myths arising from friends and family which can be greatly influential. The potential toxic side effects of chemotherapy in clinical trials often prevents many patients from participating in clinical trials, especially so for the experimental therapies. 

The complexity of protocols or consent forms for which participants must sign can also induce anxiety. Documents which contain dense paragraphs of text or complicated clinical terminology may confuse patients and cause concern in assuming there are a vast number of risks or potential side effects that could occur. 

The fear of randomisation has also been identified as one of the most commonly cited reasons by cancer patients for declining trial participation. The idea that a patient will randomly be assigned to multiple treatment types can cause a fear of experimentation, which again may cause patients to believe they are open to a number of potential adverse events. 

Demographic and socioeconomic disparities

The demographic and socioeconomic disparities that arise in cancer clinical trial enrollment is not a new challenge in the field. The underrepresentation of ethnic minorities is a consistent issue which needs to be addressed urgently in research. Despite patients of minority racial/ethnic backgrounds (in the US) demonstrating a willingness to participate in clinical trials, it has been emphasised that this population continues to “lack easy access to participate”. 

Between 2016 and 2018, it was found that “almost three-quarters of the clinical trial participants for [cancer] were white patients, while black patients comprised merely 3.1%”. It was suggested this could be attributed in part to the disproportionate population distribution and cancer incidence in the USA. However, another study inferred that statistics such as this can be due to an “inadequate estimation of the scope of the problem” which can result in limited resources being used to address the issue. Certain minority groups may be more likely to favour alternative treatment based on religious beliefs or tradition which conflicts with medical intervention. 

One of the most consistent and largest disparities in cancer enrollment is the age of participants. The likelihood of higher comorbid burdens often results in older patients failing to pass the inclusion/exclusion criteria for clinical trials. The fear of experimental treatment impacting pre-existing health could be another potential reason for the limited number of older patients recruited. However, in cancer types which typically occur in older populations, it is critical to represent this population accurately in clinical trials. 

The level of education that fluctuates between cancer patients also creates a level of disparity with regards to willingness to participate. The 2016-2018 study found that “[cancer] survivors with high school or lesser education were more likely to participate compared to those with college education”. Why this is the case is yet to be fully understood, however it could be suggested that those more educated may be more aware of the risks associated with participating and weigh up risk vs benefit in greater detail. 

Studies have shown that patient populations with historically lower financial resources are often underrepresented in cancer clinical trials. Financial barriers for this particular group can include: Routine care costs; time away from work for travel/clinic visits; transportation; unknown adverse effects resulting in expense relating to treatment. Similarly, patients with higher socioeconomic status appear to be enrolled in cancer clinical trials more frequently. The impact of this disparity contributes to a lack of data about the efficacy of certain therapies for a population that is not equally represented.

How are these issues being addressed?

Research into the issue of patient enrollment is ongoing and continues to be a slow process. However a number of solutions have been developed based on insights from the studies investigating the barriers to enrollment.

A number of potential solutions have been suggested to address the financial burden of cancer clinical trials including the following:

• Clarify definitions of routine care costs 

• Provide patients with clear and transparent information about potential trial-related financial burden and resources available to help, such as financial navigation and counseling

The clarification of care cost and financial burden is an important part of forming trust between patient and clinicians, providing transparency of the entire process. A clear, detailed explanation of potential costs and financial support is more likely to encourage patients to participate, rather than limited information as to the financial impact on them. 

• Allow for ethically appropriate financial assistance for trial-related out-of-pocket expenses

• Conduct additional research to help recognise and address the financial burden of clinical trial

Understanding the emotional patient journey throughout the stages of their treatment pathway is another strategy some organisations are implementing in order to improve recruitment numbers. The emotional pathway is said to follow the patient’s emotional state, attitudes and opinions throughout their treatment journey – in turn this can reflect where they turn for support and seek information. 

Collecting and using this data is critical to patient recruitment in oncology due to the range of experiences that people have with the disease. Discussions with clinicians regarding the challenges they’re facing, what they’re concerned about and how they’re reacting to treatment regimens can provide clinicians with a structure of how to best support the patient with regards to addressing their concerns and potentially suggest clinical trial enrollment based on the interaction. 

Charlotte Di Salvo, Lead Medical Writer
PharmaFeatures