In response to the rising cost of cancer drugs, the National Comprehensive Cancer Network (NCCN) recently developed a value framework, known as “Evidence Blocks,” to grade the efﬁcacy, safety, evidence quality, evidence consistency, and affordability of treatments included in its clinical guidelines. The value scores were available for 55 of the 69 new cancer drugs approved by the US Food and Drug Administration from 2007 to 2016. Overall, the treatment costs for 95% of new cancer medicines in NCCN clinical guidelines were scored as “very expensive” or “expensive”. In multivariable ordered logistic regression models, there was no association between the affordability of new cancer drugs and efﬁcacy and safety data available in clinical guidelines. Most guideline-recommended drugs were subject to annual list price increases exceeding inﬂation. High cancer drug prices are a major public health concern (1). Over Using the Drugs@FDA database, we identified all new cancer the past two decades, the inflation-adjusted price per life-year drugs approved by the US Food and Drug Administration (FDA) be- gained of new cancer drugs has more than tripled (2), and the fi- tween January 2007 and December 2016, and we matched ap- nancial burden of treatment has been associated with increased proved indications to NCCN treatment guidelines. The NCCN mortality (3) and nonadherence (4). In response, various value Evidence Blocks are scored by guideline committees based on five frameworks have been proposed, including by the American components of guideline-recommended treatments—efficacy, Society of Clinical Oncology (5), European Society for Medical safety, evidence quality, evidence consistency, and affordability— Oncology (6), and others (7) to inform shared decision-making using a standardized scale from 1 (least favorable) to 5 (most about cancer therapy choices. Application of these frameworks favorable) (9). For example, for efficacy, a score of 5 signifies that suggests that many new drug treatments do not provide clinically the regimen/agent is highly effective (often providing long-term meaningful benefits (8). Recently, the National Comprehensive survival advantage or curative potential), while a score of 1 signi- Cancer Network (NCCN) developed a value framework (“Evidence fies that the regimen/agent provides symptomatic benefit only. Blocks”) to accompany its clinical practice guidelines, which are For affordability, a score of 5 signifies that the affordability of the among the most widely used in oncology (9). Unlike other frame- drug or regimen is considered high (ie, very inexpensive), while a works, the NCCN Evidence Blocks explicitly include an score of1 signifiesthat the drug or regimenisvery expensive. “affordability” criterion alongside more traditional criteria such as Affordability is defined by the NCCN as an estimate of the overall a drug’s known benefits and risks; in addition, the NCCN Evidence total cost of a therapy, including drug cost, administration, infu- Blocks aim to assess all evidence available in guidelines, including sions, supportive care, and toxicity monitoring and management. postmarketing studies. In this study, we sought to examine the as- We extracted the value scores and whether the drug had a sociation between the affordability criterion and the efficacy, “preferred” designation among the NCCN-recommended treat- safety, and quality of evidence underlying new drugs recom- ment options as of December 2017. To calculate inflation- mended in the NCCN clinical practice guidelines. We also ana- adjusted price changes, we obtained wholesale acquisition costs lyzed temporal changes in list price increases of new drugs. from the RedBook (Truven Health Analytics) and Memorial Received: January 22, 2018; Revised: March 20, 2018; Accepted: March 29, 2018 © The Author(s) 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com Downloaded from https://academic.oup.com/jncics/article-abstract/2/2/pky016/5026704 1of 3 by Ed 'DeepDyve' Gillespie user on 21 June 2018 2of 3 | JNCI J Natl Cancer Inst, 2018, Vol. 0, No. 0 (a) 100% 75% 53% 50% 31% 25% 9% 7% 0% 0% Palliative (1) Minimally effective (2) Moderately effective (3) Very effective (4) Highly effective (5) (b) 100% 75% 60% 50% 27% 25% 13% 0% 0% 0% Highly toxic (1) Moderately toxic (2) Mildly toxic (3) Occasionally toxic (4) Usually no meaningful toxicity (5) (c) 100% 69% 75% 50% 25% 25% 5% 0% 0% 0% Very expensive (1) Expensive (2) Moderately expensive Inexpensive (4) Very inexpensive (5) (3) (d) 100% 75% 60% 50% 24% 16% 25% 0% 0% 0% Poor quality (1) Low quality (2) Average quality (3) Good quality (4) High quality (5) (e) 100% 75% 58% 50% 24% 18% 25% 0% 0% 0% Anecdotal only (1) Inconsistent (2) May be consistent (3) Mainly consistent (4) Highly consistent (5) Figure 1. National Comprehensive Care Network (NCCN) Evidence Block scores for new cancer drugs approved by the Food and Drug Administration between 2007 and 2016. A–E) The efﬁcacy, safety, affordability, evidence quality, and evidence consistency domains, respectively, of the NCCN Evidence Blocks. Corresponding numerical scores are listed parenthetically on the x-axes. NCCN ¼ National Comprehensive Cancer Network. Sloan Kettering’s DrugAbacus (7) and monthly inflation rates other) (10). Statistical analyses were performed using Stata (CPI-U) from the US Department of Labor’s Bureau of Labor (version 12.0; StataCorp), and all P values were two-sided, Statistics. Ordered logistic regression was used to assess the with values of less than .05 considered statistically association between affordability and other value scores. All significant. models also included a continuous variable for time trends Fifty-five of the 69 new cancer drugs approved by the FDA and indicator variables for orphan drug designation (granted between 2007 and 2016 were recommended and scored in the for drugs treating rare diseases affecting fewer than 200 000 NCCN guidelines (Supplementary Tables 1 and 2, available on- people per year) and reimbursement type (Medicare Part B or line). Among these drugs, the mean values were 3.6 (efficacy), Downloaded from https://academic.oup.com/jncics/article-abstract/2/2/pky016/5026704 by Ed 'DeepDyve' Gillespie user on 21 June 2018 T. J. Hwang et al. | 3 of 3 Table 1. Predictors of NCCN Evidence Blocks score for affordability In conclusion, treatment costs for 95% of new cancer medi- from multivariable ordered logistic regression model cines in the NCCN clinical guidelines were scored as “very expensive” or “expensive,” and most drugs were subject to an- Characteristic OR (95% CI) P nual list price increases exceeding inflation—raising questions about the ability of patients to access drugs recommended in Approval year 0.59 (0.45 to 0.79) <.001 NCCN clinical guidelines. We also found that the affordability of NCCN score: Efﬁcacy* new cancer drugs was not associated with the efficacy and safety 2Ref. data available in clinical guidelines. However, under current law, 3 0.89 (0.17 to 4.62) .89 4 0.12 (0.01 to 1.34) .09 Medicare and Medicaid generally cover all FDA-approved cancer 5 0.03 (0.00 to 1.00) .05 drugs, as well as unapproved uses listed in drug compendia. NCCN score: Safety* Policies to better align drug expenditures with value could allow 2Ref. public payers to reduce spending on low-value therapies so that 3 0.23 (0.02 to 2.25) .21 limited resources may be redirected to treatments that offer 4 0.37 (0.03 to 4.28) .42 patients better outcomes. NCCN score: Evidence Quality* 3Ref. 4 0.38 (0.07 to 2.05) .21 Funding 5 –† .71 This work was supported by the Laura and John Arnold NCCN score: Evidence Consistency* 3Ref. Foundation (no grant number). PORTAL is also supported by 4 4.58 (0.34 to 61.7) .25 grants from the Harvard Program in Therapeutic Science 5 –† .86 and the Engelberg Foundation. Orphan drug designation Yes 0.94 (0.16 to 5.56) .94 No Ref. Notes Payable by Medicare Part B Affiliations of authors: Program on Regulation, Therapeutics, Yes 0.37 (0.07 to 1.92) .24 and Law (PORTAL), Division of Pharmacoepidemiology and No Ref. Pharmacoeconomics, Department of Medicine, Brigham and Preferred guideline position Women’s Hospital, Boston, MA (TJH, ASK, BG); Institute of Yes 1.04 (0.21 to 5.10) .96 Cancer Policy, King’s College London, London, UK (BG). No Ref. The funding organizations had no role in the design or con- *There were no drugs that received scores of 1 for Efﬁcacy, 1 or 5 for Safety, 4 or duct of the study, in the collection, analysis, or interpretation of 5 for Affordability, 1 or 2 for Evidence Quality, and 1 and 2 for Evidence the data, or in the preparation, review, or approval of the manu- Consistency. Similar results were obtained in bivariate ordered logistic regres- script. ASK has received unrelated research support from the sion modeling (to account for potential overﬁtting). CI ¼ conﬁdence interval; FDA Office of Generic Drugs and Division of Health NCCN ¼ National Comprehensive Cancer Network; OR ¼ odds ratio. †Not estimable. Communication (2013–2016) outside the submitted work. BG reports no conflicts of interest. TJH reports prior employment 3.1 (safety), 3.9 (evidence quality), 3.9 (evidence consistency), by Blackstone and Bain Capital, which have invested in health and 1.8 (affordability). Fourteen (25%) drugs were scored as “very care companies. expensive,” and 38 (69%) as “expensive” (Figure 1). Similar pro- portions of drugs with vs without a preferred guideline position References were scored as “very expensive” or “expensive” (94% vs 95%). In 1. Kesselheim AS, Avorn J, Sarpatwari A. The high cost of prescription drugs in multivariable analyses, approval year was the only statistically the United States: Origins and prospects for reform. JAMA. 2016;316(8): significant predictor of affordability, with affordability scores 858–871. declining over time (odds ratio [OR] ¼ 0.59, 95% confidence in- 2. Memorial Sloan Kettering Cancer Center. Monthly and median costs of can- cer drugs at the time of FDA approval 1965–2016. J Natl Cancer Inst. 2017; terval [CI] ¼ 0.45 to 0.79, P < .001). There was no evidence of an 109(8):djx173. association between the scores for affordability with efficacy, 3. Ramsey SD, Bansal A, Fedorenko CR, et al. Financial insolvency as a risk fac- safety, evidence quality, or evidence consistency (Table 1). tor for early mortality among patients with cancer. J Clin Oncol. 2016;34(9): 980–986. Overall, the median inflation-adjusted annual list price increase 4. Dusetzina SB, Winn AN, Abel GA, Huskamp HA, Keating NL. Cost sharing and was 3% (interquartile range ¼ 1%–8%). adherence to tyrosine kinase inhibitors for patients with chronic myeloid Our study has several strengths and limitations. This report leukemia. J Clin Oncol. 2014;32(4):306–311. uses data from NCCN’s cancer value framework, which may be- 5. Schnipper LE, Davidson NE, Wollins DS, et al. Updating the American Society of Clinical Oncology value framework: Revisions and reﬂections in response come increasingly accessed by physicians and patients given to comments received. J Clin Oncol. 2016;34(24):2925–2934. the broad use of NCCN guidelines in clinical practice. A limita- 6. Cherny NI, Sullivan R, Dafni U, et al. A standardised, generic, validated ap- tion is that we focused on drugs that were included and proach to stratify the magnitude of clinical beneﬁt that can be anticipated from anti-cancer therapies: The European Society for Medical Oncology scored in NCCN guidelines, so while our study included 80% of Magnitude of Clinical Beneﬁt Scale (ESMO-MCBS). Ann Oncol. 2015;26(8): new FDA-approved cancer drugs during the study period, 1547–1573. these findings may not be generalizable to other therapies. As 7. Memorial Sloan Kettering Cancer Center. Evidence Based Drug Pricing Project. http://www.drugabacus.org/. Accessed March 20, 2018. the NCCN continues to integrate the Evidence Blocks across 8. Tibau A, Molto C, Ocana A, et al. Magnitude of clinical beneﬁt of cancer drugs its clinical guidelines, scores may be available for more drugs approved by the US Food and Drug Administration. J Natl Cancer Inst. 2018; in the future. Finally, additional predictors of drug affordabil- 110(5):djx232. 9. Carlson RW, Jonasch E. NCCN Evidence Blocks. J Natl Compr Canc Netw. 2016; ity, such as patients’ insurance status, may influence the in- 14(5 Suppl):616–619. terpretation of NCCN’s affordability scores for certain 10. Prasad V, Wang R, Aﬁﬁ SH, Mailankody S. The rising price of cancer drugs—a patients. new old problem? JAMA Oncol. 2017;2017;3(2):277–278. Downloaded from https://academic.oup.com/jncics/article-abstract/2/2/pky016/5026704 by Ed 'DeepDyve' Gillespie user on 21 June 2018
JNCI Cancer Spectrum – Oxford University Press
Published: Jun 1, 2018
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