Financial toxicity: A ubiquitous condition in patients with cancer

In their seminal work in the 1990s, Link and Phelan posited that social conditions, especially socioeconomic factors, represent a chronic risk factor for disease and poor disease outcomes through the mechanism of lack of access to economic and health care resources.¹ Their work followed the famous Whitehall studies from England, begun in 1967, which demonstrated the stark disparities in mortality between individuals from different social classes.^{2, 3} Within a broader scientific and sociological effort to understand how an individual’s position in society may affect their health, the concept of financial toxicity can be viewed as a successor to these prior landmark efforts, helping to illuminate how economic stress can exacerbate the already devastating impact of a cancer diagnosis for individuals.

Financial toxicity refers to the negative consequences of economic strain and pressure related to a cancer diagnosis. As noted by Zafar and Abernethy in 2013, financial toxicity reflects the “patient-level impact of the cost of cancer care.”⁴ Subsequent research has highlighted the relevance of this factor in the patient's clinical and psychological experience.^5-7 A study by Knight and colleagues showed that patients with financial toxicity were less likely to undergo recommended tests and fill their medications.⁵ Ramsey and colleagues showed how severe financial distress requiring bankruptcy protection was associated with a 79% increased risk of death.⁶ The relevance of financial toxicity as a risk factor for adverse experiences in patients with cancer has now been highlighted by the introduction of a validated and widely used tool for measuring its prevalence.^{8, 9}

Although the phenotype and consequences of financial toxicity have been characterized in the cancer population, much less work has been done evaluating its nature in patients enrolled in clinical trials. Patients participating in cancer clinical trials face financial and insurance considerations similar to those receiving standard treatment. A prospective cohort study in patients with metastatic colorectal cancer found that nearly three in four patients experienced financial hardship within the first year after diagnosis.¹⁰ Thus, characterizing the prevalence of financial toxicity is important for understanding and interpreting clinical trial results. Moreover, clinical trial cohorts represent a more distinct and selected set of patients. Trial cohorts are generally younger, less diverse, and healthier than the general cancer population.^11-13 This limits confidence in the applicability of trial findings across all patient groups. However, trial cohorts can also represent opportune databases for examining health care disparities research questions. In particular, patients in clinical trials inherently have access to care, which eliminates access to care as a confounding variable—a common issue in cancer population-based studies.

In a recent issue of Cancer, Durbin and colleagues offer a novel contribution to this topic.¹⁴ Recognizing that information about financial toxicity in patients participating in early-phase clinical trials is limited, the authors conducted a prospective evaluation of the prevalence of financial toxicity in a cohort of patients enrolled in phase I and phase I/II trials at Massachusetts General Hospital from 2021 through 2023. Key findings among the eligible patients, nearly all of whom had metastatic disease (93.8%), included that 34% were identified as experiencing financial toxicity at the time of their initial enrollment to an early-stage trial. Moreover, the experience of financial toxicity at the time of initial enrollment to a trial was greater among those with lower levels of income and education. Furthermore, financial toxicity was correlated with quality of life, coping strategies, and concerns about access to resources. Importantly, the authors found no evidence that clinical outcomes (e.g., survival) differed between patients with and without financial toxicity. The results were limited by the inclusion of a predominantly White population and the lack of follow-up assessments of financial toxicity over time.

The relevance of these findings is, first and foremost, in characterizing the extent of financial stress among patients enrolling in early-phase trials. More than one-third of all patients met this criterion, an estimate that aligns with prior evidence.^{5, 15} This statistic needs to be viewed in the context of the patient experience. Few adult patients participate in cancer clinical trials, with recent estimates ranging from 6% to 8%.¹⁶ Patients who participate in trials report being motivated by altruism and the desire to contribute to the scientific discovery of new treatments, thus helping to provide new therapies for future generations.¹⁷ An even larger portion, however, aims to find the best treatment for their disease.¹⁸ Patients express enormous hesitancy about trial participation because of concerns about the uncertainty of receiving experimental treatment, even as trials provide an opportunity to receive the newest treatments that may give hope for their prognosis.¹⁸ Such hesitancy is wholly understandable when considering the experience of a metastatic disease diagnosis intersecting with financial anxiety.

The findings by Durbin and colleagues shed light on how commonly patients in financial distress participate in early-phase cancer clinical trials. Indeed, an important consideration for many patients is how to pay for the costs of cancer clinical trial participation. In this context, the finding that 34% of patients in early-phase clinical trials report financial toxicity at cancer diagnosis suggests a sizeable contribution to clinical research from this population.¹⁴ However, what remains unknown is whether this adequately represents the proportion of patients in the cancer population who would otherwise meet early-phase trial inclusion criteria. Prior research on income disparities in access to trials suggests that this proportion is even greater in the general population because trials tend to enroll individuals with more resources. One study showed that concern about how to pay for the ancillary costs of trial participation was 24% among those with annual household incomes >$100,000, rising to 53% for those with annual household incomes <$20,000.¹⁸ Likely for this reason, lower income patients are approximately 30% less likely to participate in clinical trials compared to their higher income counterparts.^{18, 19}

As such, a key strategy could be to provide patients the financial support to alleviate the direct and indirect costs of trial participation. Models to provide financial support have been proposed and range from reimbursement for the measurable costs of trial participation to providing wage payment reimbursement to compensate patients for their time, effort, and study contributions.²⁰ Such an approach would need to be appropriately calibrated to limit the possibility that financial support could inappropriately induce patients to participate, under the US Common Rule. However, if done appropriately, it could help remove cost considerations as a barrier to trial participation.

The evaluation of correlations with quality of life (QOL) is relevant to the increasing importance of the patient's voice in predicting a range of outcomes. Patient-reported outcomes are associated with treatment symptoms, treatment adherence, and even clinical outcomes, including survival.^21-23 The finding in Durbin et al. that QOL indicators were associated with financial toxicity at the initiation of treatment is consistent with a recent study by Vaidya and colleagues, who demonstrated that patients from socioeconomically deprived areas were more likely to report physical and symptom levels of distress.²⁴ An increased understanding of the relationship between financial toxicity at treatment presentation and QOL could help inform the understanding about important QOL findings from treatment trials.

The observation of no outcome differences among the patients in the Durbin study is limited in part by the evaluation of patients in early-phase trials with shorter life expectancy from a heterogeneous set of diseases. But it could also reflect the benefits of the receipt of guideline-based care in trials. As noted by Link and Phelan, individual-level economic variables assert a chronic negative effect on individual health because of a lack of access to economic and health care resources.¹ In this setting, participation in a clinical trial provides a leveling effect in clinical risk by overcoming, at least temporarily, the chronic negative effect of lack of resources.

This latter observation has potential policy implications. The possible resolution of disparities in clinical outcomes in the setting of uniform access to guideline-based care suggests that the universal provision of quality care to individuals with disease, of the sort provided in clinical trials, is vital for resolving healthcare disparities for socioeconomically vulnerable patients. Policymakers aiming to address socioeconomic disparities in cancer outcomes should therefore recognize the critical role of supporting access to quality oncologic care for all patients, regardless of their socioeconomic status.

The author declares no conflicts of interest.