DAA Marketing Payments From Manufacturers Linked to Physician Prescribing Patterns

Deborah Marshall, MD

Credit: Conquer Cancer

New research is calling attention to a significant association between pharmaceutical company marketing payments related to direct-acting antivirals (DAAs) and physician prescription patterns for hepatitis C virus (HCV) treatment.¹

Findings showed physicians who received payments related to ledipasvir/sofosbuvir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir were more likely to prescribe these DAAs compared with those who did not receive payments. Additionally, significant positive associations were observed between the number of general payments and both the number of claims and Medicare spending across the 4 DAAs.¹

According to the World Health Organization, globally, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring each year. The HCV treatment landscape was fundamentally altered with the introduction of the first DAA in 2011, which facilitated sustained virologic response and subsequent HCV cure. While high prices were initially a major barrier to treatment access for many patients, costs have generally decreased due to the introduction of generic versions of these medicines.²

“The expensive cost of DAA treatment imposes a substantial financial burden on the US healthcare spending and patients,” Deborah Marshall, MD, an assistant professor in the department of radiation oncology and in the Blavatnik Family Women's Health Research Institute at the Icahn School of Medicine at Mount Sinai, and colleagues wrote.¹ “The recent introduction of several newer, less expensive DAAs has resulted in heightened competition among pharmaceutical companies and increased marketing activities of DAAs to physicians including HCV guideline authors."

To assess the associations between industry payments and physician DAA prescription practices, investigators analyzed data from 3 publicly accessible databases: the Centers for Medicare and Medicaid Services Medicare Part D, Open Payments, and Physician Compare. They focused on ledipasvir/sofosbuvir (Harvoni; Gilead Sciences), elbasvir/grazoprevir (Zepatier; Merck), sofosbuvir/velpatasvir (Epclusa; Gilead Sciences), and glecaprevir/pibrentasvir (Mavyret; AbbVie), as they are currently recommended for initial HCV treatment in the US.¹

In order to encompass physicians who could prescribe DAAs, investigators extracted data on the 30-day standardized number of claims (including refills), Medicare spending, and total number of supply days associated with each DAA reported by physician prescribers from the Medicare Part D database from 2014-2021. General payments related to the 4 DAAs were collected from the Open Payments Database for the same period. Of note, the study included only physician prescribers because the Open Payments Database covered payments to physicians.¹

Of 5044 eligible physicians who prescribed > 10 claims per year for any of the DAAs, 73% were gastroenterologists/hepatologists. Investigators noted > 91.3% of the physicians prescribed ledipasvir/sofosbuvir after its 2014 approval, whereas only 7.3% and 14.7% prescribed elbasvir/grazoprevir and glecaprevir/pibrentasvir, respectively. Of a total of $10.1 billion in Medicare spending for the 4 DAAs, 84.0% ($8.4 billion) was for ledipasvir/sofosbuvir and 11.5% ($1.2 billion) was for sofosbuvir/velpatasvir.¹

Of all eligible physicians in the study, 94.3% received ≥ 1 payment from the DAA manufacturers over the 8 years. Gilead Sciences made payments to 32.3% of physicians for ledipasvir/sofosbuvir, totaling $12.2 million, and to 35.6% of physicians for sofosbuvir/velpatasvir, totaling $19 million. For elbasvir/grazoprevir, 52.4% of physicians received payments totaling $5.1 million, and for glecaprevir/pibrentasvir, 61.5% of physicians received payments totaling $11.3 million.¹

Investigators pointed out notable differences in payment patterns by different DAA manufacturers. Merck and AbbVie made 93.2% and 92.3% of their payments as gift payments, whereas Gilead Sciences allocated about 1/3 of their payments for ledipasvir/sofosbuvir and sofosbuvir/velpatasvir as compensation payments to a limited number of physicians. The median annual payments per physician were higher for ledipasvir/sofosbuvir ($141; interquartile range [IQR], $105–$4638) and sofosbuvir/velpatasvir ($136; IQR, $194–$6353) than those for elbasvir/grazoprevir ($37; IQR, $18–$91) and glecaprevir/pibrentasvir ($43; IQR, $25–$116).¹

Multivariable logistic generalized estimating equation models adjusting for covariates at the individual physician-year level revealed physicians who received payments related to each DAA were significantly more likely to prescribe them:

• Ledipasvir/sofosbuvir (odds ratio (OR), 1.81; 95% confidence interval (95% CI), 1.62–2.02; P < .001)
• Elbasvir/grazoprevir (OR, 1.96; 95% CI, 1.57–2.43; P <.001)
• Sofosbuvir/velpatasvir (OR, 2.24; 95% CI, 1.96–2.57; P <.001)
• Glecaprevir/pibrentasvir (OR, 1.68; 95% CI, 1.46–1.94; P <.001)

Investigators also observed significant positive associations between the number of general payments and both the number of claims and Medicare spending across the four DAAs. Additional sensitivity analyses indicated significant associations between the payments made to physicians 1 year prior to their claims and their prescription patterns for all 4 DAAs.¹

Investigators outlined multiple limitations to these findings, including potential inaccuracies and underreporting in the payment data reported by manufacturers; the inability to include physicians who prescribed ≤ 10 claims for DAAs under Medicare Part D due to database limitations; and the lack of generalizability to non-Medicare beneficiaries.¹

“This study found that the payments related to DAAs from the manufacturers to the physicians who frequently prescribed DAAs to Medicare beneficiaries were significantly associated with their prescribing patterns for DAAs in the US,” investigators concluded.¹

References

1. ^{Murayama A, Sigel KM, Tarras ES, et al. Pharmaceutical industry payments and prescriptions of direct acting antiviral drugs for hepatitis C virus infection. Liver International. https://doi.org/10.1111/liv.16111}
2. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed September 25, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}