Hepatitis C treatment has gone through a revolution in the last 5 years. Treatment durations have dropped from 48 to 12 weeks, and success rates have improved dramatically. However, treatment costs have sky-rocketed accordingly, and access to care has become a significant issue, particularly for lower socioeconomic individuals and groups. Eligible veterans should have access to healthcare services through the Veterans Administration (VA). However, rates of Hepatitis C virus (HCV) screening, diagnosis, and access to treatment vary considerably for veterans across the US.
A recent study published in Medical Care by Basile Njei, MD MPH and colleagues at Yale University School of Medicine has shown that access (defined as at least one prescription refill) to these new HCV treatments, called Direct-Acting Antivirals (DAAs), varied significantly by rural-urban designation and by section of the country where care was being provided. Access rates topped out around 53% in rural areas of the Midwest and bottomed out just over 40% for patients in Southern rural areas. Rural-urban gaps in accessing these medications were easier to spot in some regions and revealed themselves after adjustment for socioeconomic and demographic variations in the Southern states.
These trends didn’t always follow the stereotypes of who has the best access to care. They tell a story about treatment variability within one of the most regulated and standardized healthcare delivery systems in the country. The geographic inequalities that exist in a system such as this, even when social and economic variables are controlled, indicate that there are some seriously-deterministic pressures in play when it comes to deciding who gets the care and who doesn’t.
So why should we care about fluctuations in access to these medications across the country?
Hepatitis C
Just so we’re all on the same page, Hepatitis C (HCV) is a viral liver infection. It is transmitted via blood from another infected individual – through birth by a mother already infected, needle-sharing, needle-stick injuries, and (more rarely) sexual contact or use of infected tattoo equipment. In the acute stages, there may be no medical issues or symptoms. However, 75-85% of infected individuals will develop chronic infection (greater than 6 months to lifelong). The CDC estimates that there are around 41,000 new cases of acute hepatitis per year, and approximately 2.4 million individuals living with HCV infection in the US.
These numbers are notoriously difficult to estimate, however, because about half of those who get infected are even aware of their status [pdf] and screening rates are still far below recommendations. Without treatment, around 20-25% of patients with chronic HCV infection will eventually develop cirrhosis and further complications such as hepatocellular carcinomas. It is also the leading indication or cause of liver transplants in the US, which costs the system as well as individuals.
Public Service Announcement: Screening for HCV
Individuals born between 1945-1965 are five times as likely to have an HCV infection, many of whom are symptom-free and unaware they have any liver problems at all. In fact, 75% of all HCV infections in the US are in people born in that time window (so-called “Boomers”). The CDC, as well as pretty much every other organization of note, recommends that everyone in this age range gets tested. It’s easy and could save your life, by preventing serious liver damage or even liver cancer. For a full list of groups at elevated risk who should obtain a screening test for HCV if they haven’t already, look here.
Direct-Acting Antivirals
Before the development of the latest innovation in HCV treatment, the standard of care was a combination of pegylated interferon α (pegIFNα) and ribavirin (RBV). This treatment regimen lasted anywhere from 24-48 weeks (5.5-11 months) and was known for low treatment success rates (approximately 40% after 11 months of continuous therapy) and considerable side effects – both of which also contributed to poor treatment completion rates.
To solve this conundrum, new therapies were eventually developed that directly targeted viral production by interrupting different stages in the viral life cycle. The first of these, boceprevir and telaprevir, were approved by the FDA in 2014. Both of these drugs were designed as inhibitors of the NS3A/NS4B protease enzyme encoded in the HCV genetic code [pdf].
Currently, there are four classes of DAAs, defined by their mechanism of action and therapeutic target. These are nonstructural proteins 3/4A (NS3/4A) protease inhibitors (PIs), NS5B nucleoside polymerase inhibitors (NPIs), NS5B non-nucleoside polymerase inhibitors (NNPIs), and NS5A inhibitors. Compared with the older HCV treatments, DAA therapies are more effective (upwards of a 95% “cure” or sustained virologic response (SVR) [pdf]), easier to tolerate, and significantly shorter in duration (~12 weeks). In addition, these newer therapies are highly effective in traditionally (i.e., with pegIFNα and RBV) more problematic patients, including those with cirrhosis, HIV coinfection, renal failure, or prior HCV treatment experience [pdf].
Unfortunately, all of this innovation and progress comes with a pretty dramatic tradeoff. The initial enthusiasm in the medical community has been tempered by two major issues: the extraordinarily high price of DAAs and the barriers patients and clinicians face in obtaining access to these drugs [pdf]. Provider and patient advocates often point to the disparities between the “wholesale acquisition costs” and the estimated production costs of these drugs. For example, Gilead Sciences makes a 12-week course of the drug sofosbuvir (tradename: Sovaldi) available for approximately $84,000 while the cost of production is estimated to be between $68 and $136 [Figure 2; pdf]. Sofosbuvir is often sold as a combination therapy with ledipasvir (tradename: Harvoni) which is priced at $94,500 for a 12-week course [Figure 3A; pdf].
Pharmaceutical companies justify these margins as necessary to recoup the significant costs of researching and developing this new class of drug. And while the numbers are stark, it’s important to acknowledge that these drugs would not have existed without the R&D work done by these companies, and they are well within their rights to set their prices accordingly. Manufacturers of DAAs have also been very proactive in providing assistance to uninsured and underinsured patients through programs known as Patient Assistance Programs (PAP).
For medical providers, the process for obtaining approval from the PAPs and/or insurance companies and their pharmacy benefits management (PBM) partners can be time-intensive, complicated, and exhausting. Even once insurance approval is received, it may take an exceptionally long time until access is finally green-lit. This only serves to further decrease the overall treatment rate.
The VA can limit the direct effect of high prices on the patients in their system. However, providers still have to seek approval for treatment coverage, through a VA-specific PBM‘s formulary. Just like other PBMs, this is based on treatment eligibility, and various other factors [pdf] thought to optimize the likelihood of treatment success. The criterion affecting a final decision whether to provide treatment is not transparent; however, leading to questions about what drives these decisions and, thereby, overall rates of access.
Geography of Access and the Birth Cohort (1945-1965)
The cohort discussed in the recent Medical Care publication were veterans receiving care from the VA and born between 1945 and 1965 since that group is at peak risk of hepatitis C infection. The study by Dr. Njei and colleagues divided records from the Veteran Birth Cohort into 4 geographic regions: Midwest, South, West, and Northeast and characterized patients as receiving services in urban, micropolitan, rural, or isolated settings (the latter three categories were collapsed and designated as rural areas). The focus of the study was measuring the proportion of those who successfully received DAAs, defined as filling at least one prescription, out of all hepatitis C diagnoses between January 2014 and December 2016.
The study found that things are not equal across the country and there’s still a gap in access between rural and urban areas – but not always in the same direction. The lowest incidence of access to DAA treatment was in Southern rural towns (just 40.1%), and the highest access rate was actually in the Midwest’s most isolated areas (52.9%). Furthermore, the divide between rural and urban areas’ access to DAAs is not equal across the country – with the Midwest and West regions showing large gaps in crude (i.e., unadjusted) comparison. When adjusted for demographics and past medical history, a rural-urban area gap shows up in the South as well. Even with adjustment, however, the Midwestern rural areas still performed with the best rates of DAA access across the rest of the country, setting the bar for everyone else with approximately 27% greater odds of access than Southern urban areas.
Achieving equality and equity in care delivery is everything these days. And in a system like the VA one might be fooled into an expectation that access would be pretty similar across the board. However, studies like this one show us that the part of the country and the density of the population where you live seem to have a hand in determining your ability to receive life-changing, potentially life-saving, treatments. It won’t be easy, but something tells me when can do better.
Ben King