Payer perceptions of the use of real-world evidence in oncology-based decision making.

BACKGROUND: Randomized controlled trials (RCTs), the gold standard of safety and efficacy evidence, are conducted in select patients that may not mirror real-world populations. As a result, healthcare decision makers may have limited information when making formulary decisions, especially in oncology, given accelerated regulatory approvals and niche patient populations. Real-world evidence (RWE) studies may help address these knowledge gaps and help inform oncology formulary decision making. OBJECTIVE: To assess US payer perceptions regarding the use and relevance of RWE in informing oncology formulary decisionmaking. METHODS: A national survey containing single-answer, multiple-answer, and free-response questions evaluated 4 key areas: (1) the value of RWE, (2) barriers to RWE, (3) sources of RWE, and (4) use of RWE in outcomes-based contracting. The survey was distributed to 221 US payers through the Academy of Managed Care Pharmacy (AMCP) Market Insights program in February 2020. Ten additional respondents were invited to discuss the survey results. The survey results were presented primarily as frequencies of responses and were evaluated by the respondent's plan size, type, and geography (regional vs national). Differences in responses for categorical data were compared using a Pearson Chi-Square or a Fisher's Exact test. Two-tailed values are reported and a level of ≤ 0.05 was used to indicate statistical significance. RESULTS: The national survey had a 45.9% response rate, with 106 payers responding. Most were from managed care organizations (MCOs; 47.5%) and pharmacy benefit managers (PBMs; 37.4%), with 54.5% from large plans (≥ 1 million lives) and 45.5% from small plans (< 1 million lives). Respondents were largely pharmacists (89.9%), with 55.6% overall indicating their job was a pharmacy administrator. Most (84.9%) used RWE to inform formulary decisions in oncology to support comparative effectiveness in the absence of head-to-head clinical trials (4.1 on a scale of 1 = Not At All Useful to 5 = Extremely Useful) and validation of National Comprehensive Cancer Network (NCCN) recommendations (4.0). Almost half (41.5%) used RWE results to inform off-label usage decisions. Payers valued RWE pre-launch to inform formulary and contracting decisions and desired real-world comparative effectiveness data post-launch to validate coverage decisions. However, the majority of payers (54.7%) did not conduct their own real-world studies. Commonly considered RWE sources included claims data (79.2%), medical records (68.9%), prospective cohort studies (60.4%), patient registries (36.8%), and patient outcome surveys (33.0%). Barriers to conducting internal RWE studies included the lack of resources and personnel, analytic capabilities, appropriate in-house data, and perceived value in conducting analyses. Payers expressed interest in using outcomes-based contracting in oncology; few have direct experience, and operationalizing through value measurement is challenging. CONCLUSIONS: RWE providing comparative treatment data, validation of NCCN treatment recommendations, and information on off-label usage are appreciated pre launch with post launch validation. DISCLOSURES: Pfizer provided funding for this research, and employees of Pfizer led the development of the survey and contributed to the manuscript as authors. Arondekar and Niyazov are employees of Pfizer; Oderda, Biskupiak, and Brixner are managers of Millcreek Outcomes Group and were paid as consultants on this project. Burgoyne was a consultant for Pfizer on this project. Malone was paid by Millcreek Outcomes as a consultant on this project.

Important Group Differences on the Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: The Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) is important to gauge clinical benefit in metastatic renal cell carcinoma (mRCC). OBJECTIVES: To estimate important difference (ID) in FKSI-DRS scores that is considered to be meaningful when comparing treatment effect between groups, using mRCC trial data. METHODS: Data were derived from two pivotal phase III mRCC trials comparing sunitinib versus interferon alfa (N = 750) in first-line mRCC, and axitinib versus sorafenib (N = 723) in second-line mRCC. The change from baseline in FKSI-DRS score was examined as a function of a set of anchors using the repeated-measures model. Several anchors were evaluated: FKSI item "I am bothered by side effects of treatment," EuroQol five-dimensional questionnaire utility score, and adverse events. RESULTS: When the "I am bothered by side effects of treatment" score was used as an anchor, the ID ranged between 1.2 and 1.3 points. When change in the EuroQol five-dimensional questionnaire utility score was used as an anchor, the FKSI-DRS ID ranged between 0.62 and 0.63 points. Selecting the adverse events that corresponded to a maximum worsening in the FKSI-DRS score in either trial, the ID ranged between 0.62 and 0.74 points. CONCLUSIONS: Among patients undergoing treatment for mRCC, between-group differences in FKSI-DRS scores as low as 1 point might be meaningful.

Pregnancy Outcomes after Treatment for Cervical Cancer Precursor Lesions: An Observational Study.

OBJECTIVE: To examine whether surgical procedures involving the uterine cervix were associated with pregnancy outcomes, including preterm birth, low birth weight, cesarean delivery and pregnancy loss. DESIGN: Population-based observational study nested in retrospective matched cohort. SETTING: Kaiser Permanente Northwest integrated health plan in Oregon/Washington, U.S.A. POPULATION: Female health plan members age 14-53 years with documented pregnancies from 1998-2009. Women with prior excisional and ablative cervical surgical procedures (N = 322) were compared to women unexposed to cervical procedures (N = 4,307) and, separately, to those having undergone only diagnostic/biopsy procedures (N = 847). METHODS: Using log-linear regression models, we examined risk of adverse pregnancy outcomes in relation to prior excisional or ablative cervical surgical procedures. We stratified excisional procedures by excision thickness. We evaluated for confounding by age, body mass index, race, smoking history, previous preterm birth, and parity. RESULTS: We found a positive association between excisional treatment > = 1.0 cm and the outcomes preterm birth and low birth weight (preterm birth unadjusted risk ratio [RR] = 2.15, 95% confidence interval [CI] 1.16-3.98 for excisions ≥1.0 cm compared to unexposed women), particularly in women who delivered within one year of surgery (RR = 3.26, 95% CI 1.41-7.53). There was no clear association between excisional treatment and cesarean delivery, and treated women did not have a substantially higher risk of dysfunctional labor. Ablative treatment was not associated with low birth weight, preterm birth, or cesarean delivery but was associated with pregnancy loss (RR = 1.43, 95% CI 1.05-1.93 vs. unexposed women). Analyses using the diagnostic procedures comparison group produced similar results. CONCLUSION: Women with > = 1.0 cm excisional treatment had elevated risk of preterm birth and low birth weight when compared to unexposed women and women with cervical diagnostic procedures. This suggests that increased risk derives from the treatment itself, not from other characteristics. The observed association between pregnancy loss and ablative surgical treatment requires further investigation.

Pregnancy after treatment for cervical cancer precursor lesions in a retrospective matched cohort.

OBJECTIVE: To determine whether treatments for precancerous cervical lesions were associated with lower pregnancy rates compared to rates in unexposed women and women who had a diagnostic cervical biopsy or colposcopy. DESIGN: Matched, retrospective cohort study. SETTING: Kaiser Permanente Northwest (KPNW), an integrated healthcare delivery system in Oregon and Washington. PATIENTS: Women 14 to 53 years old with KPNW enrollment during the period 1998 through 2009. MAIN OUTCOME MEASURE: Pregnancy after exposure or index date. Pregnancy was defined using a validated algorithm and electronic medical records data. RESULTS: We observed 570 pregnancies following cervical treatment in 4,137 women, 1,533 pregnancies following a diagnostic procedure in 13,767 women, and 7,436 pregnancies in a frequency-matched sample of 81,435 women unexposed to treatment or diagnostic procedures. After adjusting for age and contraceptive use, we observed a higher rate of pregnancies in the treatment group compared to unexposed women (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.30-1.55), but no difference in pregnancy rates between the treatment and diagnostic procedure groups (HR = 1.03, 95% CI: 0.93-1.13). CONCLUSIONS: No adverse effects of cervical procedures on subsequent rates of pregnancy were observed in this cohort with up to twelve years of follow-up time.

Estimating health and economic benefits from using prescription omega-3 fatty acids in patients with severe hypertriglyceridemia.

Patients with increased triglyceride levels compared to those with normal levels are at higher risk for coronary heart disease. In patients with severe (≥500 mg/dl) hypertriglyceridemia (SHTG), clinical trials have demonstrated that prescription ω-3 fatty acids (P-OM3s) 4 g/day can decrease triglyceride levels by 45%. However, the precise health and economic benefits of decreasing SHTG with P-OM3 are unknown. We used the previously validated Archimedes model to simulate a 20-year trial involving subjects 45 to 75 years old with SHTG. The trial consisted of an intervention arm (P-OM3 4 g/day) and a control arm. Simulation results for the control arm indicated that subjects with SHTG are at about 2 times higher risk for myocardial infarction than those with normal triglyceride levels. Using estimates from previous epidemiologic studies and meta-analyses with OM3s, the model predicted 29% to 36% decreases in various measurements of adverse cardiac events for the intervention arm. The model also predicted a decrease in ischemic stroke of 24% (95% confidence interval 15 to 33). For the 20-year simulated trial, the cost per quality-adjusted life-year gained for the currently available P-OM3 approved by the Food and Drug Administration was $47,000. Results remained robust under different clinical assumptions. In our model P-OM3 was effective in decreasing triglyceride levels and cardiovascular disease risk in patients with SHTG. In conclusion, P-OM3 medication is cost effective in our simulated trial and comparable to other cost-effective cardiovascular interventions.