APPENDIX A

Algorithm for measurement of anti-VEGF treatment

When possible, aflibercept, ranibizumab, pegaptinib, and bevacizumab were identified using product-specific (Healthcare Common Procedure Coding System) HCPCS codes. However, because bevacizumab may not necessarily be billed using a product-specific HCPCS code, and because ranibizumab and aflibercept were not issued product-specific HCPCS codes until after they were available on the market, this study also relied on non-specific HCPCS codes to identify these therapies. Using the payment amounts and service dates recorded on administrative claims, this study followed the methodology of previously-published studies that have distinguished between probable ranibizumab and bevacizumab medical claims that have been coded with non-specific HCPCS codes[1, 2, 3]. This method was also used to identify probable aflibercept medical claims that have been coded with non-specific HCPCS codes.

Table 1 details the coding, payment, and service date criteria that were used to identify aflibercept, ranibizumab, pegaptinib, and bevacizumab.

Table 1: Criteria to identify aflibercept, ranibizumab, pegaptinib, and bevacizumab *

Timeframe / Code / Code Type / Definition/criteria
Ranibizumab
06/30/2006 – 01/01/2009 / J3490 or J3590 / HCPCS / Unclassified injection or Unclassified biologics
67028 / CPT / Intravitreal injection of a pharmacologic agent
$1,500 + / Cost / Cost reported on claim with HCPCs code must fall within this range.
01/01/2007 – 12/31/2007 / C9233 / HCPCS / Injection, ranibizumab, 0.5 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
01/01/2008 – Present / J2778 / HCPCS / Injection, ranibizumab, 0.1 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
Bevacizumab
02/26/2004 – 12/31/2005 / C9214* / HCPCS / Injection, bevacizumab, per 10 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
01/01/2005 – Present / J3490 or J3590 / HCPCS / Unclassified injection or Unclassified biologics
67028 / CPT / Intravitreal injection of a pharmacologic agent
$1 to $350 / Payment / Payment reported on claim with HCPCs code must fall within this range.
07/01/2004 – 07/01/2006 / S0116 / HCPCS / Bevacizumab, 100 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
01/01/2005 – Present / J9035 / HCPCS / Injection, bevacizumab, 10 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
10/01/2009 – 12/31/2009 / Q2024 / HCPCS / Injection, bevacizumab, 0.25 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
01/01/2010 – Present / C9257 / HCPCS / Injection, bevacizumab, 0.25 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
Aflibercept
11/18/2011 – present / J3490 or J3590 / HCPCS / Unclassified injection or Unclassified biologics
67028 / CPT / Intravitreal injection of a pharmacologic agent
$1,500 + / Cost / Cost reported on claim with HCPCs code must fall within this range.
04/01/2012 – 06/30/2012 / C9291 / HCPCS / Injection, aflibercept, 2 mg vial
67028 / CPT / Intravitreal injection of a pharmacologic agent
07/01/2012 – 12/31/2012 / Q2046 / HCPCS / Injection, aflibercept, 1 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
01/01/2013 – Present / J0178 / HCPCS / Injection, aflibercept, 1 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
Pegaptanib
01/01/2005 – 12/31/2005 / C9128 / HCPCS / Injection, pegaptanib sodium, per 0.3 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
07/01/2005 – 06/30/2006 / S0198 / HCPCS / Injection, pegaptanib sodium, 0.3 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent
01/01/2006 – Present / J2503 / HCPCS / Injection, pegaptanib sodium, 0.3 mg
67028 / CPT / Intravitreal injection of a pharmacologic agent

CPT = Current Procedural Terminology; HCPCS = Healthcare Common Procedure Coding System

*HCPCS code C9214 was deleted on 12/31/2004. Claims with code C9214 were identified in the year following its deletion to ensure that data collection was comprehensive

APPENDIX B

Codes and specific criteria used to measure covariates

Covariate / Criteria
Non-melanoma cancer / Identified by the presence of at least one inpatient or two non-diagnostic outpatient medical claims (on different days, at least 30 days apart) with a diagnosis of non-melanoma cancer (ICD-9-CM 140.xx-171.xx, 173.xx-208.xx, 209.0x-209.3x, and 209.7x) in any diagnosis position
Dyslipidemia / Identified by the presence of at least one inpatient or non-diagnostic outpatient medical claim with a diagnosis of dyslipidemia (ICD-9-CM 272.xx) in any position; or ≥2 outpatient prescription claims for antihyperlipidemic medications (bile acid sequestrants, fibric acid derivatives, intestinal cholesterol absorption inhibitors, statins, or nicotinic acid derivatives)
Retinal vein occlusion / Identified by the presence of at least one inpatient or non-diagnostic outpatient medical claim with a diagnosis of retinal vein occlusion (ICD-9-CM 362.35 or 362.36) in any diagnosis position
Diabetic macular edema / Identified by the presence of at least one inpatient or non-diagnostic outpatient medical claim with a diagnosis of diabetic macular edema (ICD-9-CM 362.07 OR [362.01-362.06 AND 250.5x]) in any diagnosis position
Cataracts / Identified by the presence of at least one inpatient or non-diagnostic outpatient medical claim with a diagnosis of cataract (ICD-9-CM 366.xx) in any diagnosis position
Glaucoma / Identified by the presence of at least one inpatient or non-diagnostic outpatient medical claim with a diagnosis of glaucoma (ICD-9-CM 365.xx) in any diagnosis position
Non-steroidal anti-inflammatorydrugs / Identified by the presence of atleasttwooutpatientprescriptionclaims for an NSAID (bromfenacsodium, celecoxib, diclofenac, etodolac, fenoprofencalcium, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolactromethamine, lansoprazole/naproxen, meclofenamatesodium, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetinsodium, or valdecoxib)
Glucocorticoids / Identified by the presence of at least two outpatient prescription for a glucocorticoid (betamethasone, cortisone acetate, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, triamcinolone)
Photodynamic therapy / Identified by the presence of at least one inpatient or one non-diagnostic outpatient medical claim with a procedure code for photodynamic therapy (CPT 67221 or 67225) in any procedure position
Laser photocoagulation therapy / Identified by the presence of at least one inpatient or one non-diagnostic outpatient medical claim with a procedure code for laser photocoagulation (CPT 67220 or 0017T; ICD-9-CM 14.24) in any procedure position
Cataract surgery / Identified by the presence of at least one inpatient or one non-diagnostic outpatient medical claim with a procedure code for cataract surgery (CPT 66820-66984; ICD-9-CM 13.11-13.69) in any procedure position
Intravitreal steroid injection / Identified by the presence of at least one inpatient or one non-diagnostic outpatient medical claim with a HCPCS code for dexamethasone (C9256, J1094, J1100, J7312), triamcinolone (J3300, J3301, J3302, J3303), or fluocinolone (J7311); to ensure the steroid is for an intravitreal injection, the presence of a medical claim for intravitreal injection (CPT 67028) on the same date as the steroid claim also required

CPT = Current Procedural Terminology; HCPCS = Healthcare Common Procedure Coding System; ICD-9-CM = International Classification of Diseases, 9th Revision, Clinical Modification

Figure 1. Mean days between each of the first five intravitreal anti-VEGF injections, calculated among patients with at least five injections

* The overall mean days between each of the first five injections was 42.0 for aflibercept patients and 38.4 for ranibizumab patients, a difference of 3.6 days (95% CI = 2.1 to 4.9).

Red dashed lines drawn at 30 days and 60 days represent the expected time between aflibercept injections based on package insert: once-monthly for the first three months followed by once every other month for aflibercept

Error bars represent one standard deviation

The number of contributing patients for calculations were – Aflibercept 178, Ranibizumab = 622

REFERENCES

  1. Levinson DR. Medicare Payments for Drugs Used to Treat Wet Age-Related Macular Degeneration. Department of Health and Human Services Office of Inspector General. 2012 April: OEI-03-10-00360.
  2. Levinson DR. Review of Medicare Part B Avastin and Lucentis Treatments for Age-Related Macular Degeneration. Department of Health and Human Services Office of Inspector General. 2011 Sept: A-01-10-00514.
  3. Curtis LH, Hammill BG, Schulman KA, Cousins SW. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol. 2010 Oct;128(10):1273-9.