Despite an estimated 3.9 million individuals infected with hepatitis C in the United States, only a small fraction have successfully undergone antiviral therapy (44
). Barriers are pervasive at multiple junctures in the process from HCV screening to successful completion of antiviral treatment. First, significant barriers exist in proceeding from a positive screen for HCV to being referred to a clinic that provides antiviral therapy (46
). Barriers, such as ongoing psychiatric and SA comorbidities, continue to exist after patients have gained entry into HCV treatment centers (1
). Finally, the difficult treatment regimen and adverse side effects diminish treatment completion rates (49
This study was an effort to overcome the most prevalent barriers at the second juncture in this funneling-down process. This randomized clinical trial evaluated the impact of an INT on eligibility for PegIFN therapy among HCV patients who were originally deferred from treatment owing to two highly prevalent barriers to treatment: MH and SA comorbidities. We developed an intervention that was guided by the Stages of Change model, and employed case management and motivational-enhancing counseling strategies, which were delivered by the hepatology psychologist on a monthly basis by telephone and in person for up to 9 months. All participants in the study received enhanced SC, which included standardized screening instruments, written treatment recommendations addressing the comorbidity that led to deferral from treatment at baseline, a book on hepatitis C, and follow-up clinic visits at 3-month intervals for re-evaluation of treatment eligibility by hepatologists. Patients who participated in the intervention were 2.4 times more likely to overcome barriers and be deemed eligible for PegIFN treatment compared to patients who received standard care. This study is the first investigation to demonstrate the efficacy of an integrated care approach on HCV treatment eligibility rates in the context of a clinical trial design.
In a previous retrospective analysis of treatment deferral rates at our hepatology clinic, only 16% of patients originally deferred from PegIFN treatment owing to MH/SA subsequently became eligible for therapy in the future (1
). As we designed the current trial to of er enhanced SC procedures, we anticipated relatively higher eligibility rates (~25%) for participants in the SC condition. However, this was not the case. Despite enhancement of standard procedures, the eligibility rate for standard care participants was not significantly higher than the results of the earlier study (18% vs. 16%). Thus, written treatment recommendations, educational materials, and frequently scheduled follow-up visits, while necessary, may be insuficient tactics for improving adherence to hepatologists’ treatment recommendations. Clearly, additional interventions beyond these procedures will be needed to assist patients in making requisite behavioral changes to improve treatment eligibility.
Integrated care models are becoming increasingly common for the management and treatment of other conditions, such as HIV (27
). With increased recognition of the similarities between the HIV and HCV populations, as well as the medication regimens, a similar paradigm shift in disease management of HCV may be warranted (25
). The VA system, with an infrastructure that lends itself well to integrated care models, has taken the lead in spear-heading interdisciplinary management strategies to improve the care of veterans with HCV and comorbid MH/SA (12
). Several VA-based observational studies have demonstrated that veterans with MH/SA comorbidities can access and successfully complete PegIFN therapy when managed within an integrated care context (14
). In one study, a psychiatric clinical nurse specialist was co-located in the HCV clinic to provide SA treatment and stabilize psychiatric symptoms, while preparing patients for antiviral therapy (29
). Patients were screened for MH/SA disorders and referred as needed to the psychiatric clinical nurse specialist who provided case management, referrals, counseling, and psychotropic medications. Similar to our study, treatment was individually tailored to meet the needs of each patient. The results of their retrospective analysis were very congruent with our findings: 47% of patients who were followed by the psychiatric clinical nurse specialist became eligible for PegIFN therapy compared to 16% of patients who did not participate in the integrated care. Although these findings were very encouraging, they were limited by the retrospective, non-randomized, study design.
In this study, the intervention was designed to be individually tailored to address each patient’s reason for deferral, motivation level, and availability of community resources. Although the absence of a manualized intervention may be perceived as a limitation, it is also a strength of the study as it allowed the interventionist to meet the unique needs of each patient. Given the heterogeneity of deferral reasons (i.e., psychiatric, alcohol, illicit drugs, dual diagnoses) and differing levels of patient motivation, it is imperative to match counseling strategies to each patient and their motivational level (35
). Another important factor to consider is the availability of MH/SA services in a patient’s local community, which could be effected by health insurance status and rural vs. urban living.
This study employed standard operating procedures of clinical trial methodology and represents a significant strength of the study. The RCT design allowed us to empirically test for differences between the treatment conditions, something that previous investigations of integrated care models in HCV have been unable to do. The use of valid and reliable screening instruments increased the quality and consistency of hepatologists’ treatment decisions. Standardized procedures (e.g., universal written treatment recommendations, masking procedures, standard intervals between clinic visits) reduced the risk of bias, which could have affected our primary outcome. These standardized procedures increase the credibility of our findings and instill greater confidence that the group differences in treatment eligibility were due to the intervention, and not other confounding variables.
Limitations of this study include the absence of treatment fidelity measures to assess the quality of the intervention and the possibility of experimenter bias influencing the clinicians’ treatment eligibility decisions. The absence of audio-taping of intervention sessions precludes conducting qualitative analyses to better understand why the intervention worked. Despite tremendous effort to mask clinicians who were responsible for assessment of the primary outcome, it is possible that investigator–clinician interactions during follow-up visits could have influenced clinicians’ decisions. However, we were vigilant to this issue from the start and instituted several procedures to minimize unblinding; at no time during the study did any clinician or patient report violation of masking procedures. Similarly, it is theoretically possible that the intervention simply coached patients to appear like appropriate candidates, without actually changing their underlying MH/SA issues. We are currently following patients in a clinical observational study to collect treatment uptake and outcome data. Although this study is not complete, the preliminary data suggest that: (a) other non-MH/SA issues (e.g., medical issues, awaiting triple therapy) may contribute to further postponement of antiviral treatment, and (b) the majority of patients who start HCV treatment appear to tolerate and persist on the medical regimen. These limited data on treatment uptake and outcomes are based on very small numbers, and final conclusions should be based on a complete data set and after the new antiviral regimens are implemented.
This study can serve as a springboard for future investigations. Although this trial demonstrates the efficacy of a multi-component intervention, subsequent analyses need to elucidate individual components or active ingredients responsible for improvements in eligibility rates. Inclusion of treatment fidelity measures, such as audio-taping, would allow us to home in on active treatment ingredients. The cost-effectiveness of intervention delivery needs to be examined. While this interventionist was a PhD-level clinical psychologist co-located in the hepatology clinic, it is likely that others (e.g., nurses, social workers) could be trained to deliver similar interventions in community-based clinics, where it may be less feasible to staff a, MH/SA provider. Future studies should also determine the optimal length of INTs, and if different strategies work best for psychiatric vs. SA populations. Finally, investigations of novel intervention delivery methods, such as internet-based or texting approaches (54
), should also be explored. It is essential that investigators interested in developing models to improve access to care do so within the unique infrastructure and configuration of the clinical environment so that procedures are feasible and sustainable. Although the development of models to fit the unique configurations of various treatment settings poses challenges for replication and generalizability in the short run, it behooves us to discover the most appropriate models of care befitting a variety of different HCV treatment clinics, in the long run.
Given that a majority of HCV patients have yet to receive antiviral treatment, in large part due to MH/SA comorbidities, novel health service approaches, such as the one tested in this trial, need to be developed to improve disease management. Reforming our current models of care is of tremendous public health importance now, as we look forward to the next generation of antiviral therapies. Clinicians should anticipate a re-emergence of patients with MH/SA comorbidities who were previously deferred from treatment when the risk–benefit ratio dissuaded many providers and patients from attempting treatment. Triple therapy will alter the risk–benefit ratio and tip in favor of attempting treatment with a more diverse group of patients such as those included in this study. The development of innovative, cost-effective, and practical integrated care solutions is timely and urgently needed to address the scope of this public health problem. The INT developed for this trial may not generalize to all clinical settings, but will lay the groundwork for the exploration of other health service models that have the potential to increase access to, and successful treatment for a vast number of infected individuals who still await treatment.