Table 2 Characteristics of real-world data (RWD) used in FDA review packages
Therapy– Generic (US Brand name) | Approved Indication | RWD Study Design | Temporality: Retrospective/ Prospective/ Both | Purpose: Contextualization/ Comparison/ Both | Main Objective(s) | RWD Study sample size | Duration matches Trial | A-Priori Protocol | Eligibility Criteria Matched | Methods for Bias OR Missing Data Reported |
|---|---|---|---|---|---|---|---|---|---|---|
Elivaldogene autotemcel (Skysona) [20] | Early cerebral adrenoleukodystrophy (CALD) | Natural History | Retrospective | Both | - Evaluate natural history of untreated CALD - Evaluate efficacy/safety of alloHSCT in CALD | 172 | ✗ | ✓ | ✓ | ✗ |
Vutrisiran (Amvuttra) [21] | Polyneuropathy (PN) of hereditary transthyretin mediated (hATTR) amyloidosis in adults | External Placebo Control | Retrospective | Comparison | - Determine efficacy of vutrisiran in pts. with hATTR amyloidosis by evaluating effect on neurologic impairment compared to external controls | 77 | ✓ | ✓ | ✓ | ✓ |
Vosoritide (Voxzogo) [22] | Increase in linear growth in children with achondroplasia ages 5 and older with open epiphyses | Natural History | Retrospective | Comparison | - Demonstrate long term safety and efficacy | Matched at baseline: 559; Matched at 5-year: 360 | ✓ | ✓ | ✓ | ✓ |
Allogeneic processed thymus tissue- agdc (Rethymic) [23] | Immune reconstitution in pediatric patients with congenital athymia | Natural History | Retrospective | Comparison | - Assess survival at year 1 and 2 | 49 | ✓ | ✓ | ✓ | Bias: ✓ Missing data: ✗ |
Fosdenopterin (Nulibry) [24] | Molybdenum cofactor deficiency (MoCD) type A | Natural History | Both | Both | - Characterize natural history of MoCD Type A - Observe clinical outcomes, including survival | Retro: 37 Prosp:14 | ✓ | ✓ | ✓ | Bias: ✓ Missing data: ✗ |
Lonafarnib (Zokinvy) [26] | Hutchinson-Gilford progeria syndrome (HGPS) and processing deficient progeroid laminopathies (PL) | Registry-based natural history | Retrospective | Comparison | - Evaluate reduced mortality in patients with HGPS compared to matched controls | Unmatched: 81; Matched: 62 (1:1) | ✗ | ✗ | ✓ | Bias: ✓ Missing data: ✗ |
Viltolarsen (Viltepso) [27] | Duchenne muscular dystrophy | Natural History | Retrospective | Comparison | - Compare functional endpoints | 69 | ✓ | NR | ✓ | Bias: ✓ Missing data: ✗ |
Risdiplam (Evrysdi) [28] | Spinal muscular atrophy | Natural History | Retrospective | Both | - Compare proportion of patients sitting without support | NR | NR | NR | ✓ | ✗ |
Triheptanoin (Dojolvi) [29] | A source of calories and fatty acids in the treatment of long-chain fatty acid oxidation disorders (LC-FAOD) | Medical Chart Review | Retrospective | Comparison | - Historical medical record review to compare major clinical event rates | 29 | CL201:✓ CL202:✗ | ✗ | ✓ | ✗ |
Pretomanid Tablet (Pretomanid) [30] | Pulmonary extensively drug-resistant (XDR) and treatment-intolerant/nonresponsive (TI/NR) multidrug-resistant (MDR) tuberculosis in adults | Historical Control | Retrospective | Both | - Provide contextualization for efficacy rates and compare with historical control | 202 | ✗ | ✓ | ✓ | Bias: ✓ Missing data: ✗ |
Onasemnogene abeparvovec-xioi (Zolgensma) [32] | Spinal muscular atrophy (SMA) | Natural History | Retrospective | Comparison | - To compare survival at 14 months of age; and the proportion of subjects able to sit independently for = 30 s by 18 months of age. | 23 | NR | ✓ | ✓ | ✗ |
Triclabendazole (Egaten) [33] | Fascioliasis | Historical Control | Retrospective | Comparison | - Compare cure rates | 37 | ✓ | ✓ | NR | ✗ |
Stiripentol (Diacomit) [34] | Dravet syndrome | Medical Chart Review | Retrospective | Both | - Historical chart review from 2002–2012 to compare benefits/effects | 29 | ✗ | ✗ | ✓ | ✗ |
Fish oil triglycerides inj. Emulsion (Omegaven) [36] | Parenteral nutrition-associated cholestasis (PNAC) | Natural History | Retrospective | Both | - Evaluate growth of pediatric patients with PNAC on Omegaven or Intralipid; - Compare the effect and safety | Study 34: PP– 52; PM– 26 Study 35: PP– 24; PM– 15 | ✓ | ✓ | ✓ | ✓ |
Burosumab (Crysvita) [37] | X-linked hypophosphatemia (XLH) | Natural History | Retrospective | Both | - Characterize change in rickets severity over time with conventional therapy; - Comparison to uncontrolled ph II study | 52 | ✓ | ✓ | ✓ | Bias: ✓ Missing data: ✗ |
Voretigene neparvovec (Luxturna) [38] | Biallelic RPE65 mutation-associated retinal dystrophy | Medical Chart Review | Retrospective | Contextualization | - Evaluate the disease condition | 70 | ✓ | ✗ | ✓ | ✗ |
Emicizumab-kxwh (Hemlibra) [40] | Hemophilia A (congenital factor VIII deficiency) | External Control | Retrospective | Contextualization | - Document number, types, and treatment of bleeds under routine clinical practice | Cohort A: 103; Cohort B: 24; Cohort C: NR | NR | ✓ | NR | ✗ |
Vestronidase alfa-vjbk (Mepsevii) [41] | Mucopolysaccharidosis type 7 (MPS VII) | CL001: Medical Chart Review; CL002: Patient Survey | CL001: Retrospective; CL002: Retrospective history data | Contextualization | - Evaluate impact on clinical outcomes, - Identify the type and severity of clinical symptoms; impact of symptoms on functional status; inform endpoint selection for clinical studies | Study CL001: 50; Study CL002: 10 | NR | NR | ✓ | ✗ |
Cerliponase alfa (Brineura) [42] | Neuronal ceroid lipofuscinosis type 2 (CLN2) | Registry-based natural history | Retrospective | Comparison | - Compare efficacy endpoints | 69 | ✓ | ✓ | ✓ | ✗ |
Thiotepa (Tepadina) [43] | Class 3 β-thalassemia | Historical Control | Retrospective | Comparison | - Compare incidence of graft rejection following allogeneic BMT with control arm | 71 | ✓ | ✓ | ✓ | ✗ |