ALBERT

Description: BACKGROUND: We report preliminary results from a study on the out-of-pocket costs (cancer related costs not covered by healthcare insurance) for 57 lymphoma pts. To explore factors that influence out-of-pocket costs and QOL, cancer type, stage, time since diagnosis (Dx), treatment type (with or without rituximab), and age were evaluated. METHODS: Lymphoma pts provided information on out-of-pocket costs for 3-month periods after lymphoma Dx and completed the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) QOL measure. Monthly costs were evaluated. Direct medical costs are costs related to medications, hospital bills, and doctor visits. Direct non-medical costs are peripheral costs related to transportation, meals, and telephone calls. RESULTS: The majority of lymphoma pts were Caucasian (87%), married (63%), ≤ 55 years old (58%), and employed (40%). All pts were undergoing active treatment and had healthcare insurance coverage. 62% of pts had stage I-III lymphoma, 35% had stage IV, and 3% had unknown stage. Mean monthly total out-of-pocket costs for all 57 lymphoma pts were $818. Direct medical costs for HD pts were 3.2 and 1.4-fold higher than for INHL and ANHL pts, respectively. Direct non-medical costs were highest for ANHL. Total costs for pts 〈 6 months since Dx were 1.5 and 2.2-fold higher than for pts 6–12 and 〉 12 months since Dx, respectively. Total costs for pts undergoing treatment without rituximab were 1.5-fold higher than costs for pts with rituximab. Pts ≤ 55 years old had 1.4-fold higher costs than pts 〉 55 years old. QOL for pts 〈 6 months since Dx was greater than for pts ≥ 6 months since Dx (p-value =0.02). CONCLUSION: The mean monthly out-of-pocket costs were greatest for HD ($1,136), followed by ANHL ($847) and INHL ($447), and were driven primarily by direct medical costs. Though pts 〈 6 months since Dx incurred higher total costs than pts ≥ 6 months since Dx, their QOL measures were better. It is important to evaluate costs and quality of life of pts with cancer when describing the economic and psychosocial burden of cancer. Direct Medical, Direct Non-medical, and Total (Medical & Non-medical) Mean Out-of-Pocket Cost per Month N Direct Medical Out-of-Pocket Cost ($/month) Direct Non-medical Out-of-Pocket Cost ($/month) Total Out-of-Pocket Cost ($/month) All Patients 57 647 171 818 Cancer Type Hodgkin’s Lymphoma 16 972 164 1,136 Aggressive NHL 24 671 176 847 Indolent NHL 17 307 170 477 Time since diagnosis 12 months 16 341 146 487 Treatment Type With Rituximab 36 543 143 686 Without Rituximab 21 825 219 1,044 Age 55 yrs old 24 527 146 673 Quality of Life of Lymphoma Patients N FACT-Lymphoma Score p-value All Patients 60 126 Cancer Type 0.65 Hodgkin’s Lymphoma 17 126 Aggressive NHL 25 128 Indolent NHL 18 121 Cancer Stage 0.37 I–III 37 124 IV 21 126 N/R 2 149 Time since diagnosis 0.02 12 months 16 118 Age 0.28 55 yrs old 25 129

Description: Background: The accelerated approval (AA) regulation (21CFR314.510 Subpart H) is granted by the Food and Drug Administration (FDA) when drugs for serious medical illnesses are shown to be an improvement over available therapy. AA provides an option to use surrogate outcomes considered likely to predict clinical benefit. AA was initially developed to hasten access to HIV drugs, then, in 1995, AA was extended to cancer indications. Sponsors receiving AA are required to confirm clinical benefit (termed subpart H trials). Policy makers have several raised concerns: AA is no longer relevant today as the approval bar via this mechanism has been raised too high; many drugs that received AA did not complete subpart H trials; and some drugs approved by AA were subsequently found to be unsafe or ineffective. Methods: Using publicly available databases, we compared safety, efficacy, clinical development times, and subpart H completion rates for FDA-approved new molecular entities (NMEs) for hematologic and solid tumor cancers from 1995–2008. Results: 37% of all oncology NMEs received AA versus regular approval (64% during 1995–2003 and 33% during 2004–2008). Twenty oncology NMEs received FDA approval for hematologic malignancies (lymphomas, leukemias, Kaposi’s sarcoma, and myelodysplastic syndromes), accounting for 34% of regular approvals and 53% of AAs for oncology NMEs. Compared to NMEs approved for solid tumors, NMEs approved for hematologic malignancies were more likely to involve Orphan Drug indications (95% vs. 32%); to have shorter development times, defined as the interval between investigational new drug filing and marketing approval, (median 5.6 vs. 7.8 years); and to be approved based on phase II studies (65% vs. 29%). Prior to 2004, development times were similar for solid tumor and hematologic malignancy NMEs. Since 2004, development times have decreased by more than 2 years for hematologic malignancy NMEs, but not for solid tumor NMEs. 50% of NMEs approved for hematologic malignancies versus 71% of NMEs for solid tumor diagnoses are included in first-line cancer regimens in current National Comprehensive Cancer Network guidelines. Drugs approved for solid tumor and hematologic indications have similar safety profiles and efficacy; respectively, 30% and 38% carried black box warnings at initial approval, and 15% and 10% had black box warnings added post-approval. Studies confirming efficacy were completed for 89% of NMEs receiving AA for solid tumor indications versus 30% for NMEs receiving AA for hematologic malignancy indications. Concern that sponsors are not completing subpart H commitments has led the FDA to move from basing AA on final results of single-arm phase II trials to interim results of phase III trials. Conclusions: AAs for hematologic malignancy indications are less likely to complete Subpart H commitments. In the current era, development times for NMEs are shorter for hematologic malignancy versus solid tumor indications, principally related to the approval based on Phase II versus Phase III studies. Establishing a global policy that AA approval for cancer drugs should be based on interim results of phase III analyses rather than on final analyses of phase II trials may hamper development of novel therapies for hematologic malignancies. Solide tumor indications Hematologic malignancy indications 1995–2003 (n=21) 2004–2008 (n=10) 1995–2003 (n=11) 2004–2008 (n=9) Drugs receivving AA (%) 29 30 64 33 Orphan drugs (%) 24 40 100 78 Of AAs, Subpart H completion (%) 100 66 27 0 Approval based on phase II trial (%) 33 0 73 78 Median development time (years) 8.4 7.8 8.8 5.2