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 | ✓ | ✓ | ✓ | ✗ |
✗, no; ✓, yes; BMT, bone marrow transplant; CALD, cerebral adrenoleukodystrophy; hATTR, hereditary transthyretin mediated; HGPS, Hutchinson-Gilford progeria syndrome; HSCT, hematopoietic stem cell transplant; MoCD, molybdenum cofactor deficiency; MPS VII, mucopolysaccharidosis type 7; NR, not reported; PL, progeroid laminopathies; PNAC, parenteral nutrition-associated cholestasis; RWD, real-world data