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Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC): Assessment of Systemic Breast Cancer Treatment Patterns

Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC):... Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED- National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immuno- therapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I–IIIA (20 701) and stage IIIB–IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promot- ing more standardized and efficient treatment-related cancer research. Observational data from administrative claims and electronic A primary medication classification system used for obser- health records are increasingly being used to assess medication vational pharmacy data is the National Drug Code (NDC). An treatment patterns and outcomes. In oncology, operationalizing NDC is a unique identifier comprised of either nine digits (prod- medication data for research purposes is particularly complex. uct NDC) divided into two segments where the first five digits The increasing volume of medications available in practice to identify the drug manufacturer and the next four digits identify treat cancer (through breakthrough therapy, accelerated and reg- the chemical agent, or 11 digits (package NDC), which includes ular approvals) and the therapeutic applications for these medi- the product NDC with an additional two-digit suffix to identify cations are rapidly changing (1). As such, cancer medications the package size (2,3). In observational data, NDCs are mainly considered in treatment-related studies must be continuously used to document medications dispensed by a pharmacist in an updated to ensure appropriately focused assessments. outpatient setting as captured in pharmacy claims or in elec- Additionally, oncology therapies can be dispensed in multiple tronic health records. settings; therefore, complete capture of medication utilization Although NDCs have been required since 1972 for all com- frequently requires linkage across data sources (eg, practice and mercially available, US Food and Drug Administration (FDA)–ap- pharmacy claims) or healthcare systems and, thereby, an aware- proved medications, a historical guide has not been readily ness of how medications are documented in each data source. available to the research community. In the absence of a Received: September 23, 2019; Revised: November 22, 2019; Accepted: January 2, 2020 Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US. 46 Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 D. R. Rivera et al. |47 comprehensive, longitudinal NDC database, challenges abound medication dosage and/or labeling for all NDCs included as on- in identifying appropriate NDCs, particularly given NDCs are cologic agents were indicative of an oncology indication. All frequently created, discontinued, and even reassigned to other NDCs were categorized as nononcologic agents (eg, medi- completely different medications. Medications can also have cations not indicated to treat cancer or those that can be used multiple product and/or package NDCs, which can introduce to treat cancer but not in the form specified by the NDC, such as variation and, thus, increased opportunities for medication un- topical glucocorticoids). The Masterfile provides the infrastruc- der ascertainment via code omission. The accurate identifica- ture necessary to generate CanMED-NDC. tion of oncology medications via NDCs for observational assessments of systemic cancer therapy (eg, chemotherapy or Automated Updates. NDCs for established (eg, previously in- immunotherapy) is becoming increasingly important as the cluded in the NDC Masterfile) medications can change due to cancer treatment paradigm shifts from parenteral therapies pri- the introduction, modification, or discontinuation of a medica- marily to the inclusion of oral therapeutics. tion product and/or package. Additionally, each time a new Recognizing the need for a comprehensive resource to pro- medication becomes commercially available, new NDCs are in- vide standardized identification of cancer medications and rele- troduced. Therefore, in an effort to ensure CanMED-NDC vant codes, the Cancer Medications Enquiry Database (CanMED) remains timely, an automated strategy was developed. was created by the National Cancer Institute (NCI) Division of An automated algorithm references and compares the US Cancer Control and Population Sciences. CanMED includes all FDA NDC Directory with the Masterfile by brand and generic US FDAapproved cancer medications and their associated codes name for modifications. All new, modified, or discontinued in two queryable databases based on the primary pharmacy no- NDCs are flagged for dual clinical expert review and evaluation. menclature classification systems: NDC and Healthcare The algorithm is updated accordingly. For example, if the clini- Common Procedure Coding System (HCPCS). The development cal experts determine the new NDC (eg, a new product or pack- and utility of CanMED-HCPCS is described in a separate article age) is indicative of cancer treatment, then the new NDC is (4). The primary aim of this article is to introduce CanMED-NDC classified as an oncologic in the Masterfile and available in and, through an example assessment of systemic breast cancer CanMED-NDC. Conversely, if the clinical experts determine that (BC) treatment, demonstrate the combined utility of CanMED- the flagged NDC is not indicative of cancer treatment (eg, the NDC and CanMED-HCPCS. product or package was not approved for use in oncology), then the NDC is categorized as a nononcologic in the Masterfile so that it will not be flagged for review in the future. If an oncologic Methods agent NDC is no longer found to be included in the NDC Directory, the product and package NDCs are retained for his- Development of CanMED- NDC toric analyses with a discontinuation date, when available. Discovery of newly FDA-approved molecular entities (eg, Oncology Medication Inclusion Strategy medications not previously included in the Masterfile) is accom- The medication inclusion process and treatment assignment plished in a similar manner by referencing the NDC Directory has previously been described (4). Briefly, medications were weekly. Any NDC associated with a new medication, as identi- considered for inclusion in CanMED based on use as an agent in fied by generic name, is flagged for dual clinical expert review the treatment or management of cancer. As such, drugs must and evaluation. If it is determined that the medication NDC is either a) have an FDA-approved labeled indication for cancer indicative of an oncology indication, then the NDC is included treatment or symptom management, b) be present in the in the Masterfile as an oncologic agent and available in National Comprehensive Cancer Network (NCCN) guidelines for CanMED-NDC. Conversely, if it is deemed that the medication is the treatment or management of cancer, or c) carry an orphan not indicative of an oncology indication, then the NDC is in- drug indication for the treatment or management of cancer. cluded in the Masterfile as a nononcologic. Again, in future Medications designated as over the counter (OTC) are not in- comparative referencing any NDCs that have been categorized cluded; OTC medications are not approved for the treatment as a nononcologic are no longer flagged for review. and management of cancer. All included medications are assigned to a mutually exclusive treatment category: chemo- therapy, immunotherapy, hormonal therapy, and ancillary Dual Review and Maintenance. The NDC Masterfile update pro- therapy. Included ancillary medications must be required for or cess is electronically initiated when the automated algorithm directly associated with the administration or management of identifies four categories of NDCs that need additional manual oncologic therapy. Adjacent therapies such as opioids are not review: new entity NDC, new NDC, modified NDC, and removed included. The inclusion and categorization of each medication NDC. A dual manual review process on each queue is then con- is adjudicated independently by two pharmacists. Discontinued ducted which requires dual clinician agreement before changes medications and NDC codes are retained to allow for retrospec- are made to the Masterfile. The first reviewer conducts a com- tive research. prehensive review of the medication and associated NDC, after which a recommendation is submitted to the second reviewer. The second reviewer assesses the submitted materials and has NDC Identification the authority to make changes to the NDC Masterfile. Content Initial Development of NDC Masterfile. In December 2017, the disagreements are resolved by consensus. The NDC Masterfile US FDA NDC Directory and the NDC Structured Product is reviewed and maintained through this process on a regular Labelling Data Elements File (2012–2017) were accessed to create basis. System updates and algorithm refinement are ongoing to an NDC Masterfile (5,6). All NDCs associated with oncology improve the quality and efficiency of the resource. medications, as defined above, were selected by referencing this Masterfile. From the Masterfile, two subcategories of NDC were created: oncologic agents and nononcologic agents. CanMED-NDC. The data in CanMED-NDC include only those Clinical expert assessment was employed to ensure the NDCs that have been reviewed and determined to be oncologic Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 48 | J Natl Cancer Inst Monogr, 2020, Vol. 2020, No. 55 Figure 1. Observational research in oncology toolbox, Cancer Medications Enquiry Database (CanMED)-National Drug Code (NDC) interface. agents. The resulting database provides searchable features to unknown stage or if they had insufficient information to deter- find relevant NDCs for specific medications, minor and major mine molecular subtype (eg, unknown estrogen receptor [ER], drug classifications, or even treatment categories (eg, chemo- progesterone receptor [PR], or human epidermal growth factor therapy, hormonal therapy, immunotherapy, or ancillary ther- receptor [HER] 2 status). Patients were also required to have con- apy). Treatment categorization is based on Surveillance, tinuous fee-for-service Medicare Parts A (inpatient), B (outpa- Epidemiology, and End Results (SEER)*Rx, which is a tool devel- tient), and D (prescription drug) enrollment for at least oped for cancer registries to assign treatment (7). NDC searches 6 months post diagnosis, including the month of cancer diagno- can also be limited by year to identify codes that were in effect sis. Medicare claims were available through 2014. during a specific time period. Discontinued NDCs are retained CanMED was queried for NCCN guideline–recommended BC with a discontinuation date, when known, to allow for historic medications (Table 1) to identify appropriate NDC and HCPCS analyses. Variables available in the CanMED-NDC include: NDC codes (9). Medicare claims were then reviewed to identify medi- 11 (Package), NDC 9 (Product), Generic Name, Brand Name, cation utilization based on NDCs (Part D) and HCPCS (Part B). Strength, SEER*Rx Treatment Category, Major Drug Class, Minor Medications were analyzed based on treatment category: che- Drug Class, Administration Route, Package Effective Date, motherapy, immunotherapy, hormonal therapy, and ancillary Package Discontinuation Date, and Status of Product in Use therapy. Stage based on derived American Joint Committee on (Figure 1). The query results from searches are exportable to Cancer version 7 was dichotomized as stage I–IIIA and stage Excel for use with common statistical analysis packages such as IIIB–IV; stage III, not otherwise specified, was included with SAS and R. stage IIIB–IV. Hormone receptor (HR) status was classified as positive, if ER or PR positive, and negative, if ER and PR negative. Borderline ER or PR status was considered positive. Molecular Case Example subtype was classified as luminal A [HRþ/HER2]), luminal B [HRþ/HER2þ], HER2 enriched [HR/HER2þ], and triple negative As an example to showcase the potential application of [HR/HER2]. Patients with borderline HER2 status (n¼ 575) CanMED-NDC along with CanMED-HCPCS in facilitating were excluded from the molecular subtype analysis. Descriptive treatment-related observational research, SEER-Medicare, statistics were calculated by stage and molecular subtype to de- which is a linkage of the SEER Program population-based cancer scribe treatment patterns among BC patients within 6 months registry data with Medicare enrollment and claims data, were of diagnosis. analyzed to describe BC systemic therapy patterns (8). Medications assessed were identified using NCCN guidelines, which allowed for stage-specific and molecular subtype characterization. Results Female patients were included if diagnosed at age 66 years or older with a first primary BC between 2010 and 2013. Patients CanMED-NDC (11_2018 v.1.2.4) is a comprehensive database were excluded from the analysis if they had in situ (stage 0) or that includes 6860 NDC codes for oncology medications: Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 D. R. Rivera et al. |49 Table 1. CanMED Case Example: FDA Indications for BC treatment and NCCN Guideline–Directed Therapies for Stage I–IV Breast Cancer Treatment, 2018 Administration FDA Stage Stage FDA NCCN Generic Brand route approval Off label use I–IIIA IIIB-IV* indication guidelines HER2 HR: ER/PR Ado-trastuzumab emtansine Kadcyla IV 2013 — — X Yes Yes Yes — Anastrazole Arimidex Oral 1995 — X — Yes Yes — Yes Capecitabine Xeloda Oral 1998 — — X Yes Yes — — Carboplatin Carboplatin IV 1989 — X — Yes Yes — — Cisplatin Cisplatin IV 1978 — — X No Yes — — Cyclophosphamide Cyclophosphamide Both 1959 — X — Yes Yes — — Denosumab Prolia, Xgeva IV 2010 Ancillary — X Yes Yes — — Dexrazoxane Totect, Zinecard IV 1995 Ancillary, may be useful to identify X — Yes No — — multiple primaries Docetaxel Taxotere, Docefrez IV 1996 — X — Yes Yes — — Doxorubicin Adriamycin IV 1989 — X — Yes Yes — — Doxorubicin liposomal Doxil, Lipodox IV 1995 — X — Yes Yes — — Epirubicin Ellence IV 1999 — X — Yes Yes — — Eribulin Halaven IV 2010 — — X Yes Yes — — Everolimus Afinitor Oral 2009 — — X Yes Yes — — Exemestane Aromasin Oral 1999 — X — Yes Yes — Yes Fluorouracil Adrucil IV 1962 — X — Yes Yes — — Fulvestrant Faslodex IM 2002 — — X Yes Yes — Yes Gemcitabine Gemzar IV 1996 — — X Yes Yes — — Goserelin acetate Zoladex IV 1989 — X — Yes Yes — — Ixabepilone ixempra IV 2007 — — X Yes Yes — — Lapatinib Tykerb Oral 2007 — X Yes Yes Yes — Letrozole Femara Oral 1997 — X — Yes Yes — Yes Leucovorin calcium Wellcovorin IV only indicated 1952 Ancillary, may be useful to identify X — Yes No — — multiple primaries Levoleucovorin Fusilev IV 2008 Ancillary, may be useful to identify X — Yes No — — multiple primaries Megestrol acetate Megace Oral 1993 — — X Yes Yes — Yes Mesna Mesnex Oral, IV 1988 Ancillary X — Yes No — — Methotrexate Trexall Oral, IV, IM 1953 — X — Yes Yes — — Methyltestosterone Android, Testred Oral 1935 — — X Yes No — — Paclitaxel Taxol, Pacitaxel IV 1992 — X — Yes Yes — — Paclitaxel protein bound Abraxane IV 1992 — X — Yes Yes — — Palbociclib Ibrance Oral 2015 — — X Yes Yes — — Pamidronate Aredia IV 1998 Ancillary, may be useful to identify X Yes Yes — — multiple primaries Pertuzumab Perjeta IV 2012 — X — Yes Yes Yes — Raloxifene hydrocholride Evista Y 1997 — X — Yes Yes — Yes Ribociclib Kisqali Oral 2017 — — X Yes Yes — — Ribociclib/letrozole Kisqali Femara Co-Pack Oral 2017 — — X Yes Yes — — Tamoxifen Nolvadex, Soltamox Oral 1977 — X Yes Yes — Yes Testosterone enanthate Delatestryl IV 1953 — — X Yes No — — Toremifene Fareston Oral 1997 — X — Yes Yes — Yes Trastuzumab Herceptin IV 1998 — X — Yes Yes Yes — Vinblastine Velban IV 1965 — — X Yes No — — Vinorelbine Navelbine IV 1994 — — X No Yes — — *Includes stage III, NOS. FDA ¼ Food and Drug Administration; NCCN ¼ National Comprehensive Cancer Network; HER2 ¼ Human Epidermal Growth Factor Receptor 2; NOS ¼ Not Otherwise Specified; HR: ER/PR ¼ Hormone Receptor, Estrogen Receptor, Progesterone Receptor. Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 50 | J Natl Cancer Inst Monogr, 2020, Vol. 2020, No. 55 61.7 60.7 55.1 48.2 41.0 20.0 19.2 6.7 Chemotherapy Hormonal Therapy Immunotherapy Ancillary Therapy Type of Treatment Stage I-IIIA Stage IIIB-IV (derived AJCC-7 stage group) Figure 2. Percent of breast cancer patients receiving systemic therapy within 6 months of diagnosis by treatment type and stage group, Surveillance, Epidemiology, and End Results-Medicare, 2010–2014. chemotherapy (1870), immunotherapy (164), hormonal therapy NDC codes extracted from observational data. The database can (3074), and ancillary therapy (1752). be used by cancer registries to facilitate ascertainment of treat- ment from medical and pharmacy claims for case finding and collection of detailed treatment and among the broader re- Case Example search community to conduct assessments of treatment pat- terns. Utilization of the database(s) can also increase Among the defined SEER-Medicare cohort, treatment patterns comparability, replication, and standardization across cancer were evaluated in two clinically meaningful methods: treat- surveillance, epidemiology, and pharmacoepidemiology stud- ment by stage and treatment by molecular subtype. There were ies. CanMED nomenclatures can also be further linked with 23 082 BC patients included in the analyses by stage (stage I– other ontologies (eg, RxNorm) for additional applications. IIIA: 20 701 and 2381 with stage IIIB–IV). Among patients with The analysis of BC treatment trends by stage reflects what stage I–IIIA tumors, 19.2% received chemotherapy, 55.1% re- was expected. For example, in comparision with patients with ceived hormonal therapy, 6.7% received immunotherapy, and stage I–IIIA tumors, clinically significantly more patients with 60.7% received ancillary therapy (Figure 2). Among patients with stage IIIB–IV tumors received chemotherapy and immunother- stage IIIB–IV tumors, 41.0% received chemotherapy, 48.2% re- apy; receipt of hormonal therapy and ancillary medications was ceived hormonal therapy, 20.0% received immunotherapy, and comparable by stage group. The evaluation of the treatment by 61.7% received ancillary therapy during the study period. molecular subtype reflects the current approach to biomarker- Treatment patterns were additionally analyzed in 22 507 guided BC treatment and is largely concordant with treatment patients by the four relevant BC molecular subtypes: luminal A, guidelines. BC patients with the luminal A subtype, character- luminal B, HER enriched, and triple negative (Figure 3). The pri- ized by HRþ, had the greatest receipt of hormonal therapy, and mary treatment administered varied by molecular subtype. The luminal B and HER 2-enriched subtypes had greater receipt of most prominent modality for patients with luminal A tumors immunotherapy due to use of trastuzumab for HER2þ tumors. was hormonal therapy (63.4%) and for patients with triple nega- The case example demonstrated how the CanMED databases tive tumors was chemotherapy (49.6%). Roughly 43% of patients can facilitate treatment-related research. In the current study, a with luminal B tumors received either chemotherapy, hormonal broad understanding of the BC treatment landscape was of in- therapy, or immunotherapy, and HER-enriched patients were terest, which required the combiend use of both CanMED data- primarily treated with chemotherapy (56.3%) and immunother- bases. The CanMED-NDC provided the ability to ascertain apy (56.2%). treatment in data categorized by NDC such as Part D oral ther- apy claims (eg, BC hormonal therapies), and the CanMED- HCPCS provided the ability to identify systemic therapies within Discussion data sourced by HCPCS codes such as Part B (eg, chemothera- pies and immunotherapies). The use of databases was tailored The primary objective of CanMED-NDC is to provide a current, to the study question. If the study objective was to evaluate ei- comprehensive resource that provides a standardized method ther oral therapy or systemic therapy, then only the CanMED- of identifying NDC codes for systemic oncology medications or, NDC or CanMED-HCPCS database was used respectively. The conversely, the identification of medications associated with Percent (%) Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 D. R. Rivera et al. |51 HR+ ( ER+ or PR+) HR- (ER- and PR-) 80 80 74.9 69.2 56.3 56.2 60 60 44.8 43.3 42.3 40 40 30 30 10 10 4.5 HER2 Enriched Luminal B 80.0 80 72.6 70.0 70 63.4 57.7 60.0 60 49.6 50.0 50 40.0 40 30.0 30 20.0 20 13.8 6.4 10.0 10 2.8 1.9 0.0 0 Luminal A Triple Negave Figure 3. Breast cancer treatment utilization by molecular subtype, Surveillance, Epidemiology, and End Results-Medicare, 2010–2014. ER ¼ Estrogen Receptor; PR ¼ Progesterone Receptor; HR ¼ Hormone Receptor; HER2þ¼ Human Epidermal Growth Factor Receptor 2. development and utility of CanMED-HCPCS is described in a through our detailed processes to provide the most comprehen- separate article (4). Consultation with a data expert and a sive, public resource for oncology drug codes. The constantly clinician is recommended to decide which database(s) are most changing landscape of cancer treatment makes the prospective appropriate to use for a particular data source and development of the CanMED-NDC both challenging and neces- observational research study question. sary. Because of the clinician review process, there may be a lag Similar to those previously described for CanMED-HCPCS (4), time between when a new therapy is FDA approved and when it there are limitations to the CanMED-NDC that need to be con- is included in the CanMED-NDC. However, to stay as relevant as sidered. First, the development and maintenance of CanMED- possible, the CanMED-NDC will be maintained through a dual NDC are reliant on publicly available historical (2012–2017) and review process by NCI clinicians and any changes will be regu- regular data updates to online documentation provided by the larly updated. FDA. Therefore, it is possible that some historical codes were There are other limitations that researchers need to consider not available, and some fields may be left blank if unavailable when using CanMED-NDC. Certain medications, such as metho- (eg, effective or discontinuation dates). However, we aim trexate, can be used for cancer and for multiple other conditions HER 2- HER 2+ Percent (%) Percent (%) Percent (%) Percent (%) Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 52 | J Natl Cancer Inst Monogr, 2020, Vol. 2020, No. 55 unrelated to cancer (eg, treatment of rheumatoid and juvenile Notes arthritis or recalcitrant psoriasis). Users should be cautious Affiliations of authors: Surveillance Research Program, Division when including such medications in their cancer-related treat- of Cancer Control and Population Sciences, National Cancer ment analyses. It is recommended that medications with multi- Institute, Rockville, MD (DRR, AG, CJKL, LP, VIP); Health Care ple indications should accompany a cancer diagnosis Delivery Research Program, Division of Cancer Control and (International Classification of Diseases code), be a specific part Population Sciences, National Cancer Institute, Rockville, MD of an administered cancer regimen (R-CHOP), or be used in a (LE); Information Management Services, Inc., Calverton, MD (BO, cancer-specific algorithm to be considered cancer-related treat- TSM, SB). ment (10–12). For increased confidence, this recommendation The authors have no conflicts of interest reported. may be extended to any medication assessed. Researchers also need to be cognizant that identification of cancer-related therapies solely using NDC codes may lead to References underascertainment because cancer medications are also of- 1. Chen EY, Raghunathan V, Prasad V. An overview of cancer drugs approved by ten administered in an inpatient setting, which is billed used a the US Food and Drug Administration based on the surrogate end point of re- sponse rate. JAMA Intern Med. 2019;179(7):915. different coding nomenclature: HCPCS (eg, Medicare Part B) 2. Slavin M. The National Drug Code. Am J Hosp Pharm. 1972;29(6):468–470. (13). The CanMED-HCPCS was developed complementarily for 3. Slavin M. Origin, development and application of the National Drug Code. J a more complete view of medication use. The systems are in- Am Pharm Assoc. 1969;9(9):460–462. teroperable. Medications that do not have an associated 4. Rivera DR, Lam CJK, Petkov VI. Development and utility of the observational research in oncology toolbox: Cancer Medications Enquiry Database HCPCS code appear as HCPCS: “NA” in the search, and (CanMED) Healthcare Common Procedure Coding System (HCPCS). CanMED-NDC can then be queried to assess if any relevant Cosubmission with supplement. J Natl Cancer Inst Monogr. 2020;2020(55): NDCs for oral and outpatient medications are available 39–45. 5. Food and Drug Administration. National Drug Code Directory. https://www. depending on the study question. As mentioned, researchers accessdata.fda.gov/scripts/cder/ndc/. Accessed August 2, 2017. conducting administrative claims–based studies of cancer 6. US Food and Drug Administration. Structured Product Labeling (SPL) Data treatment are advised to use both the CanMED-HCPCS and Elements (NSDE). https://www.fda.gov/industry/structured-product-label- ing-resources/nsde. Accessed August 2, 2017. CanMED-NDC, when applicable, to identify a comprehensive 7. National Cancer Institute, Division of Cancer Control and Population list of relevant codes to understand exposure and longitudinal Sciences. Surveillance Research Program. SEER*Rx Interactive Antineoplastic medication utilization. Drugs Database. February 8, 2019. https://seer.cancer.gov/seertools/seerrx/. Accessed April 17, 2018. The CanMED-NDC provides a comprehensive, clinician- 8. Warren J, Klabunde C, Schrag D, et al. Overview of the SEER-Medicare data: reviewed resource for oncology drug codes that can be used for content, research applications, and generalizability to the United States el- observational research. Along with CanMED-HCPCS, this data- derly population. Med Care. 2002;40(Supplement):IV–IV18. 9. National Comprehensive Cancer Network Breast Cancer Guidelines v. 2018. base allows researchers to rigorously assess the codes required https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed to capture systemic cancer treatment in the most complete re- April 17, 2018. source currently available. The use case demonstrated how 10. Ritzwoller DP, Hassett MJ, Uno H, et al. Development, validation, and dissem- CanMED can be queried and translated into an actionable analy- ination of a breast cancer recurrence detection and timing informatics algo- rithm. J Natl Cancer Inst. 2018;110(3):273–281. sis of clinically relevant BC treatment trends by stage and mo- 11. Clarke CL, Feigelson HS. Developing an algorithm to identify history of cancer lecular subtype using SEER-Medicare data. The interactively using electronic medical records. eGEMs. 2016;4(1):1209. designed CanMED-NDC will be valuable to the research commu- 12. Warren JL, Mariotto A, Melbert D, et al. Sensitivity of Medicare claims to iden- tify cancer recurrence in elderly colorectal and breast cancer patients. Med nity and encourage standardization of medication identification Care. 2016;54(8):e47–54. for high-quality oncology treatment research. 13. Lund JL, Sturmer T, Harlan LC, et al. Identifying specific chemotherapeutic agents in Medicare data: a validation study. Med Care. 2013;51(5):e27–34. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JNCI Monographs Oxford University Press

Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC): Assessment of Systemic Breast Cancer Treatment Patterns

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Oxford University Press
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Abstract

Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED- National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immuno- therapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I–IIIA (20 701) and stage IIIB–IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promot- ing more standardized and efficient treatment-related cancer research. Observational data from administrative claims and electronic A primary medication classification system used for obser- health records are increasingly being used to assess medication vational pharmacy data is the National Drug Code (NDC). An treatment patterns and outcomes. In oncology, operationalizing NDC is a unique identifier comprised of either nine digits (prod- medication data for research purposes is particularly complex. uct NDC) divided into two segments where the first five digits The increasing volume of medications available in practice to identify the drug manufacturer and the next four digits identify treat cancer (through breakthrough therapy, accelerated and reg- the chemical agent, or 11 digits (package NDC), which includes ular approvals) and the therapeutic applications for these medi- the product NDC with an additional two-digit suffix to identify cations are rapidly changing (1). As such, cancer medications the package size (2,3). In observational data, NDCs are mainly considered in treatment-related studies must be continuously used to document medications dispensed by a pharmacist in an updated to ensure appropriately focused assessments. outpatient setting as captured in pharmacy claims or in elec- Additionally, oncology therapies can be dispensed in multiple tronic health records. settings; therefore, complete capture of medication utilization Although NDCs have been required since 1972 for all com- frequently requires linkage across data sources (eg, practice and mercially available, US Food and Drug Administration (FDA)–ap- pharmacy claims) or healthcare systems and, thereby, an aware- proved medications, a historical guide has not been readily ness of how medications are documented in each data source. available to the research community. In the absence of a Received: September 23, 2019; Revised: November 22, 2019; Accepted: January 2, 2020 Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US. 46 Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 D. R. Rivera et al. |47 comprehensive, longitudinal NDC database, challenges abound medication dosage and/or labeling for all NDCs included as on- in identifying appropriate NDCs, particularly given NDCs are cologic agents were indicative of an oncology indication. All frequently created, discontinued, and even reassigned to other NDCs were categorized as nononcologic agents (eg, medi- completely different medications. Medications can also have cations not indicated to treat cancer or those that can be used multiple product and/or package NDCs, which can introduce to treat cancer but not in the form specified by the NDC, such as variation and, thus, increased opportunities for medication un- topical glucocorticoids). The Masterfile provides the infrastruc- der ascertainment via code omission. The accurate identifica- ture necessary to generate CanMED-NDC. tion of oncology medications via NDCs for observational assessments of systemic cancer therapy (eg, chemotherapy or Automated Updates. NDCs for established (eg, previously in- immunotherapy) is becoming increasingly important as the cluded in the NDC Masterfile) medications can change due to cancer treatment paradigm shifts from parenteral therapies pri- the introduction, modification, or discontinuation of a medica- marily to the inclusion of oral therapeutics. tion product and/or package. Additionally, each time a new Recognizing the need for a comprehensive resource to pro- medication becomes commercially available, new NDCs are in- vide standardized identification of cancer medications and rele- troduced. Therefore, in an effort to ensure CanMED-NDC vant codes, the Cancer Medications Enquiry Database (CanMED) remains timely, an automated strategy was developed. was created by the National Cancer Institute (NCI) Division of An automated algorithm references and compares the US Cancer Control and Population Sciences. CanMED includes all FDA NDC Directory with the Masterfile by brand and generic US FDAapproved cancer medications and their associated codes name for modifications. All new, modified, or discontinued in two queryable databases based on the primary pharmacy no- NDCs are flagged for dual clinical expert review and evaluation. menclature classification systems: NDC and Healthcare The algorithm is updated accordingly. For example, if the clini- Common Procedure Coding System (HCPCS). The development cal experts determine the new NDC (eg, a new product or pack- and utility of CanMED-HCPCS is described in a separate article age) is indicative of cancer treatment, then the new NDC is (4). The primary aim of this article is to introduce CanMED-NDC classified as an oncologic in the Masterfile and available in and, through an example assessment of systemic breast cancer CanMED-NDC. Conversely, if the clinical experts determine that (BC) treatment, demonstrate the combined utility of CanMED- the flagged NDC is not indicative of cancer treatment (eg, the NDC and CanMED-HCPCS. product or package was not approved for use in oncology), then the NDC is categorized as a nononcologic in the Masterfile so that it will not be flagged for review in the future. If an oncologic Methods agent NDC is no longer found to be included in the NDC Directory, the product and package NDCs are retained for his- Development of CanMED- NDC toric analyses with a discontinuation date, when available. Discovery of newly FDA-approved molecular entities (eg, Oncology Medication Inclusion Strategy medications not previously included in the Masterfile) is accom- The medication inclusion process and treatment assignment plished in a similar manner by referencing the NDC Directory has previously been described (4). Briefly, medications were weekly. Any NDC associated with a new medication, as identi- considered for inclusion in CanMED based on use as an agent in fied by generic name, is flagged for dual clinical expert review the treatment or management of cancer. As such, drugs must and evaluation. If it is determined that the medication NDC is either a) have an FDA-approved labeled indication for cancer indicative of an oncology indication, then the NDC is included treatment or symptom management, b) be present in the in the Masterfile as an oncologic agent and available in National Comprehensive Cancer Network (NCCN) guidelines for CanMED-NDC. Conversely, if it is deemed that the medication is the treatment or management of cancer, or c) carry an orphan not indicative of an oncology indication, then the NDC is in- drug indication for the treatment or management of cancer. cluded in the Masterfile as a nononcologic. Again, in future Medications designated as over the counter (OTC) are not in- comparative referencing any NDCs that have been categorized cluded; OTC medications are not approved for the treatment as a nononcologic are no longer flagged for review. and management of cancer. All included medications are assigned to a mutually exclusive treatment category: chemo- therapy, immunotherapy, hormonal therapy, and ancillary Dual Review and Maintenance. The NDC Masterfile update pro- therapy. Included ancillary medications must be required for or cess is electronically initiated when the automated algorithm directly associated with the administration or management of identifies four categories of NDCs that need additional manual oncologic therapy. Adjacent therapies such as opioids are not review: new entity NDC, new NDC, modified NDC, and removed included. The inclusion and categorization of each medication NDC. A dual manual review process on each queue is then con- is adjudicated independently by two pharmacists. Discontinued ducted which requires dual clinician agreement before changes medications and NDC codes are retained to allow for retrospec- are made to the Masterfile. The first reviewer conducts a com- tive research. prehensive review of the medication and associated NDC, after which a recommendation is submitted to the second reviewer. The second reviewer assesses the submitted materials and has NDC Identification the authority to make changes to the NDC Masterfile. Content Initial Development of NDC Masterfile. In December 2017, the disagreements are resolved by consensus. The NDC Masterfile US FDA NDC Directory and the NDC Structured Product is reviewed and maintained through this process on a regular Labelling Data Elements File (2012–2017) were accessed to create basis. System updates and algorithm refinement are ongoing to an NDC Masterfile (5,6). All NDCs associated with oncology improve the quality and efficiency of the resource. medications, as defined above, were selected by referencing this Masterfile. From the Masterfile, two subcategories of NDC were created: oncologic agents and nononcologic agents. CanMED-NDC. The data in CanMED-NDC include only those Clinical expert assessment was employed to ensure the NDCs that have been reviewed and determined to be oncologic Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 48 | J Natl Cancer Inst Monogr, 2020, Vol. 2020, No. 55 Figure 1. Observational research in oncology toolbox, Cancer Medications Enquiry Database (CanMED)-National Drug Code (NDC) interface. agents. The resulting database provides searchable features to unknown stage or if they had insufficient information to deter- find relevant NDCs for specific medications, minor and major mine molecular subtype (eg, unknown estrogen receptor [ER], drug classifications, or even treatment categories (eg, chemo- progesterone receptor [PR], or human epidermal growth factor therapy, hormonal therapy, immunotherapy, or ancillary ther- receptor [HER] 2 status). Patients were also required to have con- apy). Treatment categorization is based on Surveillance, tinuous fee-for-service Medicare Parts A (inpatient), B (outpa- Epidemiology, and End Results (SEER)*Rx, which is a tool devel- tient), and D (prescription drug) enrollment for at least oped for cancer registries to assign treatment (7). NDC searches 6 months post diagnosis, including the month of cancer diagno- can also be limited by year to identify codes that were in effect sis. Medicare claims were available through 2014. during a specific time period. Discontinued NDCs are retained CanMED was queried for NCCN guideline–recommended BC with a discontinuation date, when known, to allow for historic medications (Table 1) to identify appropriate NDC and HCPCS analyses. Variables available in the CanMED-NDC include: NDC codes (9). Medicare claims were then reviewed to identify medi- 11 (Package), NDC 9 (Product), Generic Name, Brand Name, cation utilization based on NDCs (Part D) and HCPCS (Part B). Strength, SEER*Rx Treatment Category, Major Drug Class, Minor Medications were analyzed based on treatment category: che- Drug Class, Administration Route, Package Effective Date, motherapy, immunotherapy, hormonal therapy, and ancillary Package Discontinuation Date, and Status of Product in Use therapy. Stage based on derived American Joint Committee on (Figure 1). The query results from searches are exportable to Cancer version 7 was dichotomized as stage I–IIIA and stage Excel for use with common statistical analysis packages such as IIIB–IV; stage III, not otherwise specified, was included with SAS and R. stage IIIB–IV. Hormone receptor (HR) status was classified as positive, if ER or PR positive, and negative, if ER and PR negative. Borderline ER or PR status was considered positive. Molecular Case Example subtype was classified as luminal A [HRþ/HER2]), luminal B [HRþ/HER2þ], HER2 enriched [HR/HER2þ], and triple negative As an example to showcase the potential application of [HR/HER2]. Patients with borderline HER2 status (n¼ 575) CanMED-NDC along with CanMED-HCPCS in facilitating were excluded from the molecular subtype analysis. Descriptive treatment-related observational research, SEER-Medicare, statistics were calculated by stage and molecular subtype to de- which is a linkage of the SEER Program population-based cancer scribe treatment patterns among BC patients within 6 months registry data with Medicare enrollment and claims data, were of diagnosis. analyzed to describe BC systemic therapy patterns (8). Medications assessed were identified using NCCN guidelines, which allowed for stage-specific and molecular subtype characterization. Results Female patients were included if diagnosed at age 66 years or older with a first primary BC between 2010 and 2013. Patients CanMED-NDC (11_2018 v.1.2.4) is a comprehensive database were excluded from the analysis if they had in situ (stage 0) or that includes 6860 NDC codes for oncology medications: Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 D. R. Rivera et al. |49 Table 1. CanMED Case Example: FDA Indications for BC treatment and NCCN Guideline–Directed Therapies for Stage I–IV Breast Cancer Treatment, 2018 Administration FDA Stage Stage FDA NCCN Generic Brand route approval Off label use I–IIIA IIIB-IV* indication guidelines HER2 HR: ER/PR Ado-trastuzumab emtansine Kadcyla IV 2013 — — X Yes Yes Yes — Anastrazole Arimidex Oral 1995 — X — Yes Yes — Yes Capecitabine Xeloda Oral 1998 — — X Yes Yes — — Carboplatin Carboplatin IV 1989 — X — Yes Yes — — Cisplatin Cisplatin IV 1978 — — X No Yes — — Cyclophosphamide Cyclophosphamide Both 1959 — X — Yes Yes — — Denosumab Prolia, Xgeva IV 2010 Ancillary — X Yes Yes — — Dexrazoxane Totect, Zinecard IV 1995 Ancillary, may be useful to identify X — Yes No — — multiple primaries Docetaxel Taxotere, Docefrez IV 1996 — X — Yes Yes — — Doxorubicin Adriamycin IV 1989 — X — Yes Yes — — Doxorubicin liposomal Doxil, Lipodox IV 1995 — X — Yes Yes — — Epirubicin Ellence IV 1999 — X — Yes Yes — — Eribulin Halaven IV 2010 — — X Yes Yes — — Everolimus Afinitor Oral 2009 — — X Yes Yes — — Exemestane Aromasin Oral 1999 — X — Yes Yes — Yes Fluorouracil Adrucil IV 1962 — X — Yes Yes — — Fulvestrant Faslodex IM 2002 — — X Yes Yes — Yes Gemcitabine Gemzar IV 1996 — — X Yes Yes — — Goserelin acetate Zoladex IV 1989 — X — Yes Yes — — Ixabepilone ixempra IV 2007 — — X Yes Yes — — Lapatinib Tykerb Oral 2007 — X Yes Yes Yes — Letrozole Femara Oral 1997 — X — Yes Yes — Yes Leucovorin calcium Wellcovorin IV only indicated 1952 Ancillary, may be useful to identify X — Yes No — — multiple primaries Levoleucovorin Fusilev IV 2008 Ancillary, may be useful to identify X — Yes No — — multiple primaries Megestrol acetate Megace Oral 1993 — — X Yes Yes — Yes Mesna Mesnex Oral, IV 1988 Ancillary X — Yes No — — Methotrexate Trexall Oral, IV, IM 1953 — X — Yes Yes — — Methyltestosterone Android, Testred Oral 1935 — — X Yes No — — Paclitaxel Taxol, Pacitaxel IV 1992 — X — Yes Yes — — Paclitaxel protein bound Abraxane IV 1992 — X — Yes Yes — — Palbociclib Ibrance Oral 2015 — — X Yes Yes — — Pamidronate Aredia IV 1998 Ancillary, may be useful to identify X Yes Yes — — multiple primaries Pertuzumab Perjeta IV 2012 — X — Yes Yes Yes — Raloxifene hydrocholride Evista Y 1997 — X — Yes Yes — Yes Ribociclib Kisqali Oral 2017 — — X Yes Yes — — Ribociclib/letrozole Kisqali Femara Co-Pack Oral 2017 — — X Yes Yes — — Tamoxifen Nolvadex, Soltamox Oral 1977 — X Yes Yes — Yes Testosterone enanthate Delatestryl IV 1953 — — X Yes No — — Toremifene Fareston Oral 1997 — X — Yes Yes — Yes Trastuzumab Herceptin IV 1998 — X — Yes Yes Yes — Vinblastine Velban IV 1965 — — X Yes No — — Vinorelbine Navelbine IV 1994 — — X No Yes — — *Includes stage III, NOS. FDA ¼ Food and Drug Administration; NCCN ¼ National Comprehensive Cancer Network; HER2 ¼ Human Epidermal Growth Factor Receptor 2; NOS ¼ Not Otherwise Specified; HR: ER/PR ¼ Hormone Receptor, Estrogen Receptor, Progesterone Receptor. Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 50 | J Natl Cancer Inst Monogr, 2020, Vol. 2020, No. 55 61.7 60.7 55.1 48.2 41.0 20.0 19.2 6.7 Chemotherapy Hormonal Therapy Immunotherapy Ancillary Therapy Type of Treatment Stage I-IIIA Stage IIIB-IV (derived AJCC-7 stage group) Figure 2. Percent of breast cancer patients receiving systemic therapy within 6 months of diagnosis by treatment type and stage group, Surveillance, Epidemiology, and End Results-Medicare, 2010–2014. chemotherapy (1870), immunotherapy (164), hormonal therapy NDC codes extracted from observational data. The database can (3074), and ancillary therapy (1752). be used by cancer registries to facilitate ascertainment of treat- ment from medical and pharmacy claims for case finding and collection of detailed treatment and among the broader re- Case Example search community to conduct assessments of treatment pat- terns. Utilization of the database(s) can also increase Among the defined SEER-Medicare cohort, treatment patterns comparability, replication, and standardization across cancer were evaluated in two clinically meaningful methods: treat- surveillance, epidemiology, and pharmacoepidemiology stud- ment by stage and treatment by molecular subtype. There were ies. CanMED nomenclatures can also be further linked with 23 082 BC patients included in the analyses by stage (stage I– other ontologies (eg, RxNorm) for additional applications. IIIA: 20 701 and 2381 with stage IIIB–IV). Among patients with The analysis of BC treatment trends by stage reflects what stage I–IIIA tumors, 19.2% received chemotherapy, 55.1% re- was expected. For example, in comparision with patients with ceived hormonal therapy, 6.7% received immunotherapy, and stage I–IIIA tumors, clinically significantly more patients with 60.7% received ancillary therapy (Figure 2). Among patients with stage IIIB–IV tumors received chemotherapy and immunother- stage IIIB–IV tumors, 41.0% received chemotherapy, 48.2% re- apy; receipt of hormonal therapy and ancillary medications was ceived hormonal therapy, 20.0% received immunotherapy, and comparable by stage group. The evaluation of the treatment by 61.7% received ancillary therapy during the study period. molecular subtype reflects the current approach to biomarker- Treatment patterns were additionally analyzed in 22 507 guided BC treatment and is largely concordant with treatment patients by the four relevant BC molecular subtypes: luminal A, guidelines. BC patients with the luminal A subtype, character- luminal B, HER enriched, and triple negative (Figure 3). The pri- ized by HRþ, had the greatest receipt of hormonal therapy, and mary treatment administered varied by molecular subtype. The luminal B and HER 2-enriched subtypes had greater receipt of most prominent modality for patients with luminal A tumors immunotherapy due to use of trastuzumab for HER2þ tumors. was hormonal therapy (63.4%) and for patients with triple nega- The case example demonstrated how the CanMED databases tive tumors was chemotherapy (49.6%). Roughly 43% of patients can facilitate treatment-related research. In the current study, a with luminal B tumors received either chemotherapy, hormonal broad understanding of the BC treatment landscape was of in- therapy, or immunotherapy, and HER-enriched patients were terest, which required the combiend use of both CanMED data- primarily treated with chemotherapy (56.3%) and immunother- bases. The CanMED-NDC provided the ability to ascertain apy (56.2%). treatment in data categorized by NDC such as Part D oral ther- apy claims (eg, BC hormonal therapies), and the CanMED- HCPCS provided the ability to identify systemic therapies within Discussion data sourced by HCPCS codes such as Part B (eg, chemothera- pies and immunotherapies). The use of databases was tailored The primary objective of CanMED-NDC is to provide a current, to the study question. If the study objective was to evaluate ei- comprehensive resource that provides a standardized method ther oral therapy or systemic therapy, then only the CanMED- of identifying NDC codes for systemic oncology medications or, NDC or CanMED-HCPCS database was used respectively. The conversely, the identification of medications associated with Percent (%) Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 D. R. Rivera et al. |51 HR+ ( ER+ or PR+) HR- (ER- and PR-) 80 80 74.9 69.2 56.3 56.2 60 60 44.8 43.3 42.3 40 40 30 30 10 10 4.5 HER2 Enriched Luminal B 80.0 80 72.6 70.0 70 63.4 57.7 60.0 60 49.6 50.0 50 40.0 40 30.0 30 20.0 20 13.8 6.4 10.0 10 2.8 1.9 0.0 0 Luminal A Triple Negave Figure 3. Breast cancer treatment utilization by molecular subtype, Surveillance, Epidemiology, and End Results-Medicare, 2010–2014. ER ¼ Estrogen Receptor; PR ¼ Progesterone Receptor; HR ¼ Hormone Receptor; HER2þ¼ Human Epidermal Growth Factor Receptor 2. development and utility of CanMED-HCPCS is described in a through our detailed processes to provide the most comprehen- separate article (4). Consultation with a data expert and a sive, public resource for oncology drug codes. The constantly clinician is recommended to decide which database(s) are most changing landscape of cancer treatment makes the prospective appropriate to use for a particular data source and development of the CanMED-NDC both challenging and neces- observational research study question. sary. Because of the clinician review process, there may be a lag Similar to those previously described for CanMED-HCPCS (4), time between when a new therapy is FDA approved and when it there are limitations to the CanMED-NDC that need to be con- is included in the CanMED-NDC. However, to stay as relevant as sidered. First, the development and maintenance of CanMED- possible, the CanMED-NDC will be maintained through a dual NDC are reliant on publicly available historical (2012–2017) and review process by NCI clinicians and any changes will be regu- regular data updates to online documentation provided by the larly updated. FDA. Therefore, it is possible that some historical codes were There are other limitations that researchers need to consider not available, and some fields may be left blank if unavailable when using CanMED-NDC. Certain medications, such as metho- (eg, effective or discontinuation dates). However, we aim trexate, can be used for cancer and for multiple other conditions HER 2- HER 2+ Percent (%) Percent (%) Percent (%) Percent (%) Downloaded from https://academic.oup.com/jncimono/article/2020/55/46/5837301 by DeepDyve user on 14 August 2022 52 | J Natl Cancer Inst Monogr, 2020, Vol. 2020, No. 55 unrelated to cancer (eg, treatment of rheumatoid and juvenile Notes arthritis or recalcitrant psoriasis). Users should be cautious Affiliations of authors: Surveillance Research Program, Division when including such medications in their cancer-related treat- of Cancer Control and Population Sciences, National Cancer ment analyses. It is recommended that medications with multi- Institute, Rockville, MD (DRR, AG, CJKL, LP, VIP); Health Care ple indications should accompany a cancer diagnosis Delivery Research Program, Division of Cancer Control and (International Classification of Diseases code), be a specific part Population Sciences, National Cancer Institute, Rockville, MD of an administered cancer regimen (R-CHOP), or be used in a (LE); Information Management Services, Inc., Calverton, MD (BO, cancer-specific algorithm to be considered cancer-related treat- TSM, SB). ment (10–12). For increased confidence, this recommendation The authors have no conflicts of interest reported. may be extended to any medication assessed. Researchers also need to be cognizant that identification of cancer-related therapies solely using NDC codes may lead to References underascertainment because cancer medications are also of- 1. Chen EY, Raghunathan V, Prasad V. An overview of cancer drugs approved by ten administered in an inpatient setting, which is billed used a the US Food and Drug Administration based on the surrogate end point of re- sponse rate. JAMA Intern Med. 2019;179(7):915. different coding nomenclature: HCPCS (eg, Medicare Part B) 2. Slavin M. The National Drug Code. Am J Hosp Pharm. 1972;29(6):468–470. (13). The CanMED-HCPCS was developed complementarily for 3. Slavin M. Origin, development and application of the National Drug Code. J a more complete view of medication use. The systems are in- Am Pharm Assoc. 1969;9(9):460–462. teroperable. Medications that do not have an associated 4. Rivera DR, Lam CJK, Petkov VI. Development and utility of the observational research in oncology toolbox: Cancer Medications Enquiry Database HCPCS code appear as HCPCS: “NA” in the search, and (CanMED) Healthcare Common Procedure Coding System (HCPCS). CanMED-NDC can then be queried to assess if any relevant Cosubmission with supplement. 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Journal

JNCI Monographs – Oxford University Press

Published: May 1, 2020

Keywords: cancer; breast cancer; national drug code; medical oncology; chemotherapy regimen; immunotherapy; endocrine therapy

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