Table 5 Clinical and patient-reported outcomes data considered by the German Federal Joint Committee for rare diseases

1

Tisagenlecleucel (1st application area)

Oncologic diseases

Overall survival (OS)

Progression free survival (PFS), overall response rate (ORR)

n/a

FACT-Lym, SF-36, no usable data

n/a

n/a

non-quantifiable

2

Tisagenlecleucel (2nd application area)

Oncologic diseases

OS

Complete response/remission (CR), relapse free survival (RFS), MRD-negativ-status

EQ-5D VAS, no usable data

PedsQL (no useable data)

n/a

n/a

non-quantifiable

3

Gemtuzumab Ozogamicin

Oncologic diseases

OS

RFS, event-free survival (EFS), CR, rate of stem cell transplants

n/a

n/a

n/a

n/a

non-quantifiable

4

Velmanase alfa

Metabolic diseases

deaths, no events

Serum-Oligosaccharid-concentration, Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), audiological performance with pure tone audiometry (dBHL), 3-min-stair-climbing-test, FVC, FEV, 6-min-walk-test

Childhood Health Assessment Questionnaire (CHAQ), EQ-5D-5 L Index

n/a

n/a

n/a

non-quantifiable

5

Darvadstrocel

Digestive disorders

n/a

Combined remission, clinical remission, Perianal Disease Activity Index (PDAI) (partially), no reoccurrence after clinical remission, time to clinical remission, Perianal Disease Activity Index (PDAI),

Perianal Disease Activity Index (PDAI) (partially)

Inflammatory Bowel Disease Questionnaire (IBDQ)

n/a

n/a

non-quantifiable

6

Burosumab

Metabolic diseases

None

Rachitis symptoms with Rickets Severity Scale (RSS), serumphosphat, anthropometric parameters, physical resilience (6MWT), motoric abilities (Bot-2-scale), function and pain (POSNA-PODCI), Rachitis symptoms (Radiographic Global Impression of Change (RGI-C)), pain intensity (Faces Pain Scale-Revised (FPS-R))

PROMIS (function, pain, fatigue)

SF-10 (no usable data)

n/a

n/a

non-quantifiable

7

Glycerolphenylbutyrat

Metabolic diseases

None

24-h-AUC-ammoniac-concentration in the blood

n/a

SF-36, SF-15, no usable data

n/a

n/a

non-quantifiable

8

Letermovir

Metabolic diseases

OS

Clinical relevant CMV-infection, CMV-organ disease, induction of a preemptive therapy, rehospitalization (general and after CMV-reactivation), Graft-versus-Host Disease, opportunistic bacterial, viral, and fungus infections

n/a

n/a

n/a

n/a

non-quantifiable

9

Allogenic, genetic modified T-cells

Oncologic diseases

OS, median survival, 1-year survival, 10-year survival

Immune reconstruction, acute and chronic GvHD (occurrence, time to progression)

n/a

n/a

n/a

n/a

non-quantifiable

10

Brentuximab Vedotin (new application area)

Oncologic diseases

OS

PFS, ORR, hospitalization, cutane symptomatic – symptomatic domain skindex, skin changes, mSWAT-Total-Scores, complete remission (mSWAT)

EQ-5D VAS

FACT-G (quality of life), Skindex-29 (quality of life)

n/a

n/a

minor

11

Niraparib

Oncologic diseases

OS

PFS

FOSI, no usable data

no usable data

n/a

n/a

non-quantifiable

12

Cenegermin

Diseases of the eye

mortalities

Recovery of the corneal epithelium (FDA-definition), improvement of the best corrected visual acuity, progression of the lesion depth up to cornea melting, or perforation, cornea infection

EQ-5D VAS

NEI VFQ-25-score

n/a

n/a

non-quantifiable

13

Telotristatethyl

Oncologic diseases

n/a

Stool frequency, abdominal pain, compulsory stool, nausea, adequate improvement of the gastrointestinal symptoms of the carzinoid-syndrom

EORTC QLQ-C30 – diarrhea, sleeplessness

disease related worrying (EORTC QLQ-GI.NET21)

n/a

n/a

non-quantifiable

14

Midostaurin

Oncologic diseases

OS, 5-year survival

Disease free survival, CR, rate of stem cell transplants

n/a

A: n/a / B: SF-12

n/a

n/a

considerable

15

Obinutuzumab (new application area)

Oncologic diseases

OS

PFS

n/a

FACT-Lym subscale, FACT-G

n/a

n/a

non-quantifiable

16

Avelumab

Oncologic diseases

OS

PFS

EQ-5D-VAS (health state), no usable data

FACT-M, no usable data

n/a

n/a

non-quantifiable

17

Elosulfase alfa (new benefit assessment)

Metabolic diseases

n/a

Change of walk distance, change of 3MSCT, anthropometry, respiratory functioning, wheelchair use, usage of walk aids, anthropometry, respiratory functioning

MPS Health Assessment Questionnaire (MPS HAQ)

n/a

n/a

n/a

minor

18

Daratumumab (new benefit assessment, > 50 mio € limit, new application area multiple myeloma after one pretherapy)

Oncologic diseases

OS

PFS

A: EQ-5D VAS (health state), EORTC QLQ-C30 (symptom scales), B: no relevant data

A: EORTC QLQ-C30 (health state, function scales) B: no relevant data

n/a

n/a

considerable

19

Carfilzomib (new benefit assessment, > 50 mio. € limit)

Metabolic diseases

OS

PFS

EORTC QLQ-C30 (symptom scales), EORTC QLQ-MY20 (time till first deterioration)

EORTC QLQ-C30 (function scale), EORTC QLQ-MY20 (time till deterioration)

n/a

n/a

non-quantifiable

20

Inotuzumab Ozogamicin

Oncologic diseases

OS

CR, MRD-negativity rate within patients with CR/Cri, HSZT rate

EORTC QLQ-C30 (symptom scale) (time till deterioration), no usable data, EQ-5D-VAS (health state) (time till deterioration)

EORTC QLQ-C30 (quality of life, time till deterioration), no usable data

n/a

n/a

minor

21

Nusinersen

Diseases of the nervous system

OS, 5 year survival

Disease free survival, rate of complete remission, rate of stem cell transplants

n/a

No data considered

n/a

n/a

considerable

22

Cerliponase alfa

Metabolic diseases

n/a

Proportion of responder (ML-scale), decrease of the ML−/HML-scale, time to stable decrease of ≥2 points or occurrence of value 0 on ML−/HML-scale, point value change on the ML−/HML-scale, response rate ML-scale, ML-scale, MLV-scale, MLVS-scale

n/a

PedsQL (Parent report for toddlers)

n/a

n/a

non-quantifiable

23

Blinatumomab (re-evaluation after expiry of the term)

Oncologic diseases

OS

CR/CRh/CRi rate, MRD-remission rate, rate of patients with post-baseline allo-HSZT

EORTC QLQ-C30 (symptom scale, time to decrease), no usable data, ALLSS (time till decrease), no usable data

EORTC QLQ-C30 (function scale, time till deterioration), no usable data

n/a

n/a

considerable

24

Ixazomib

Oncologic diseases

OS

PFS

BPI-SF, EQ-5D-VAS

EORTC QLQ-C30, EORTC QLQ-MY20

n/a

n/a

non-quantifiable

25

Obeticholsäure

Digestive disorders

deaths, one event

Proportion of patients with ALP < 1,67 x ULN, ALP < 1,67, Bilirubin = <ULN, ALP reduction = > 15%

Pruritus (5D und VAS)

PBC-40 (quality of life)

n/a

n/a

non-quantifiable

26

Venetoclax

Oncologic diseases

OS

PFS

EQ-5D VAS, MDASI

EORTC QLQ-C30

n/a

n/a

non-quantifiable

27

Olaratumab

Oncologic diseases

OS

PFS

n/a

n/a

n/a

n/a

considerable

28

Macitentan (new benefit assessment, > 50 mio € limit)

Cardiovascular diseases

n/a

n/a

n/a

n/a

n/a

n/a

not proven

29

Ibrutinib (new application area))

Oncologic diseases

OS

PFS

EORTC QLQ-C30 (symptom scales, time to improvement/deterioration), FACIT Fatigue (time to improvement/deterioration), EQ-5D-5 L VAS (health state, time to improvement/deterioration)

EORTC QLQ-C30 (function scales, time to improvement/deterioration)

n/a

n/a

considerable

30

Teduglutid (new application area)

Digestive disorders

n/a

pE volume reduction/change, total withdrawal of pE, pE reduction

n/a

n/a

n/a

n/a

non-quantifiable

31

Tasimelteon

Diseases of the nervous system

n/a

CGI-C (health state)

UQ-dTSD (Upper Quartile Daily Total Sleep Duration), dTSD (Daily Total Sleep Time)

n/a

n/a

n/a

non-quantifiable

32

Pitolisant

Diseases of the nervous system

n/a

Epworth Sleepiness Scale (ESS), response analysis ESS, daily kataplexie-rate

frequency and severity of narcolepsy-symptoms (sleep diary), EQ-5D VAS

n/a

n/a

n/a

non-quantifiable

33

Brentuximab Vedotin (new application area)

Oncologic diseases

OS

PFS, time to first occurrence of B-symptoms (TTBS), time till onset of an allogene transplantation (TTAllo)

EQ-5D VAS

No data available

n/a

n/a

non-quantifiable

34

Carfilzomib (new application area) [annulled]

Oncologic diseases

OS

PFS

EORTC QLQ-C30 (symptom scales)

EORTC QLQ-C30 (function scales), EORTC QLQ-MY20, FACT/GOG-Ntx

n/a

n/a

minor

35

Ibrutinib (new application area)

Oncologic diseases

n/a

n/a

n/a

n/a

n/a

n/a

not proven

36

Obinutuzumab (new application area)

Oncologic diseases

OS

PFS

EQ-5D VAS

FACT-LymS, FACT-G

n/a

n/a

non-quantifiable

37

Eftrenonacog alfa

Diseases of the blood and blood-forming organs

n/a

Annualized bleeding rate

EQ-5D-Y (VAS)

Haem-A-QoL, CHO-KLAT

n/a

n/a

non-quantifiable

38

Daratumumab [annulled]

Oncologic diseases

number of deceased, median overall survival in months

PFS

n/a

No usable data

n/a

n/a

non-quantifiable

39

Albutrepenonacog alfa

Diseases of the blood and blood-forming organs

n/a

Annualized bleeding rate

n/a

Haemo-QoL

n/a

n/a

non-quantifiable

40

Migalastat

Metabolic diseases

n/a

Cardiac endpoints, cerebrovascular endpoints, mGFRiohexol, and eGFRCKD-EPI

BPI-SF (pain scale)

SF-36v2

n/a

n/a

non-quantifiable

41

Ataluren (reevaluation after date of expiration)

Musculoskeletal diseases

n/a

Walk distance 6MWT, time till persisting deterioration (10%), changes in TFT, walk distances, NSAA score, time for four stairs (up and down)

n/a

PedsQL, PODCI (Pediatric Outcomes Data Collection Instrument)

n/a

n/a

minor

42

Afamelanotid

Metabolic diseases

n/a

Sunshine exposition

Pain scale during phototoxic episodes, photoic episodes (self-reported, patient diary)

DLQI changes (overall score)

n/a

n/a

non-quantifiable

43

Ibrutinib (new benefit assessment, > 50 mio € limit)

Oncologic diseases

OS

PFS

EQ-5D VAS

FACT-G, FACT-LymS

n/a

n/a

non-quantifiable

44

Blinatumomab [annulled]

Oncologic diseases

OS

CR/CRh, MRD-response, alloHSZT eligible patients with transplantation

n/a

n/a

n/a

n/a

non-quantifiable

45

Carfilzomib [annuled]

Oncologic diseases

OS

PFS

n/a

EORTC QLQ-C30 (health state/quality of life), EORTC QLQ-MY20 (disease symptoms)

n/a

n/a

non-quantifiable

46

Ivacaftor (new application area)

Metabolic diseases

n/a

BMI change, BMI z-score change, pulmonary exacerbation, lung functioning, response analysis lung functioning

n/a

CFQ-R

n/a

n/a

minor

47

Isavuconazol

Infectious diseases

OS

Clinical response according to the data review committee

n/a

n/a

n/a

n/a

non-quantifiable

48

Asfotase alfa

Metabolic diseases

OS

Survival without invasive ventilation, anthropometric data, motoric functioning,

Pain/disability (POSNA PODCI), Pain (BPI-SF), Lower Extremity Functional Scale (LEFS)

n/a

n/a

n/a

non-quantifiable

49

Idebenon

Diseases of the eye

n/a

Changes in visual acuity, protan- and tritan-color-perception

n/a

No usable data

n/a

n/a

non-quantifiable

50

Panobinostat

Oncologic diseases

OS

PFS

n/a

EORTC-OQL-C30, QLQ-MY-20, FACT/GOG-NTX, no valid results

n/a

n/a

non-quantifiable

51

Pomalidomid (new benefit assessment, > 50 mio € limit)

Oncologic diseases

OS

PFS

EORTC QLQ-C30 (time till deterioration of symptoms), EORTC QLQ-MY20 (time till deterioration of symptoms)EORTC QLQ-C30

EORTC QLQ-C30 (time till deterioration), EORTC QLQ-MY20 (time till deterioration)

n/a

n/a

considerable

52

Sebelipase alfa

Metabolic diseases

number of survivals

Age related weight, normalization of ALT-values, LDL-C concentration

FACIT-Fatigue

Chronic Liver Disease Questionnaires (CLDQ), PedsQL

n/a

n/a

non-quantifiable

53

Lenvatinib

Oncologic diseases

OS

PFS

n/a

n/a

n/a

n/a

non-quantifiable

54

Olaparib [annulled]

Oncologic diseases

OS

PFS

n/a

Functional Assessment of Cancer Therapy-Ovarian (FACT-O)

n/a

n/a

non-quantifiable

55

Eliglustat

Metabolic diseases

n/a

Change of spleen volume in percent, morbidity

Brief Pain Inventory (BPI), Fatigue Severity Scale (FSS)Fatigue (Fatigue Severity Scale, FSS)

SF-36

n/a

n/a

non-quantifiable

56

Nintedanib (new application area)

Respiratory diseases

time till death, time till respiratory induced death

Time till first acute exacerbation, time till first adjusted acute exacerbation, annual decrease of FVC

n/a

SGRQ-(≤ −4 point)-Responder, SGRQ-changes, SGRQ-I-score (no usable data), SOBQ-score (no significant data), CASA-Q-score cough-score (no significant data)

n/a

n/a

minor

57

Ramucirumab [annulled]

Oncologic diseases

OS

PFS

EORTC QLQ-C30 (symptoms, responder analysis symptoms), EQ-5D VAS (health state)

EORTC QLQ-C30 (health related quality of life, responder analysis)

n/a

n/a

minor

58

Pasireotid (new application area)

Metabolic diseases

n/a

Biochemical controls (GH + IGF-1, GH, reduction of tumor volume (25%), improvements of symptoms

n/a

AcroQoL, no significant data

n/a

n/a

minor

59

Ataluren [annulled]

Musculoskeletal diseases

n/a

Walk distance (6MWT, MW (m)), standing up from the back position, 10 m walk, climbing 4 stairs, descending 4 stairs

n/a

Pediatric Quality of Life Inventory (PedsQL)

n/a

n/a

minor

60

Ibrutinib [annulled]

Oncologic diseases

OS

Overall response rate (IRC-assessment), PFS

n/a

No usable data

n/a

n/a

non-quantifiable

61

Alipogentiparvovec

Metabolic diseases

n/a

n/a

n/a

n/a

n/a

n/a

non-quantifiable

62

Teduglutid

Digestive disorders

n/a

Response, withdrawal of pE, shortening of pE

n/a

SBS-QoL

n/a

n/a

minor

63

Ivacaftor (new application area)

Metabolic diseases

n/a

Change of FEV, change of BMI after 8 weeks, pulmonale eyazerbation

n/a

CFQ-R (respiratory system)

n/a

n/a

minor

64

Obinutuzumab

Oncologic diseases

OS

IRC-indicated PFS

n/a

EORTC QLQ-C30 (no significant results)

n/a

n/a

non-quantifiable

65

Cabozantinib

Oncologic diseases

OS

n/a

MDASI-THY (symptom scale)

MDASI-THY (quality of life)

n/a

n/a

minor

66

Siltuximab

Oncologic diseases

OS

Tumor response (CR and PR), fading symptoms, cancellation of corticosteroid-treatment, failure of treatment

MCD-SS (symptoms), FACIT-F-(questionnaire) (Fatigue)

SF-36, Physical Component Score (PCS), Mental Component Score (MCS)

n/a

n/a

non-quantifiable

67

Elosulfase alfa [annulled]

Metabolic diseases

n/a

Walk distance changes, changes in 3MSCT

MPS Health Assessment Questionnaire (MPS HAQ)

n/a

n/a

n/a

minor

68

Cholsäure

Metabolic diseases

n/a

n/a

n/a

n/a

n/a

n/a

non-quantifiable

69

Ruxolitinib (new benefit assessment, > 50 mio € limit)

Oncologic diseases

OS

Milt volume reduction, MFSAF v2.0

MFSAF v2.1, EORTC QLQ-C30 (no usable data)

EORTC QLQ-C30 (quality of life)

n/a

n/a

considerable

70

Riociguat

Cardiovascular diseases

OS

Changes in six-minutes-walk-distance (6MWD), changes in WHO−/NYHA-functioning classes, clinical deterioration, changes in dyspnea and fatigue (borg-scale)

n/a

EQ-5d-Index, LPH-questionnaire

n/a

n/a

minor

71

Macitentan [aufgehoben]

Cardiovascular diseases

Death till EOS

Reaching first morbidity or mortality event (EOT), changes in the 6-min-walk-distance, hospitalization, changes in the Borg-dyspnea-index, improvement of the WHO/NYHA-class

n/a

SF-36

n/a

n/a

minor

72

Pomalidomid [annulled]

Oncologic diseases

OS

PFS

n/a

EORTC QLQ-C30 (No significant results in 13 of 15 subscales, physical functioning and nausea improvement), EORTC QLQ-MY20, EQ-5D (no significant results)

n/a

n/a

considerable

73

Ponatinib

Oncologic diseases

death cases, OS

Hematologic response (HR), zytogenic response (CCyR), PFS, molecular response

n/a

n/a

n/a

n/a

non-quantifiable

74

Bosutinib

Oncologic diseases

OS

Zytogenic response (CyR), molecular response, hematologic response, PFS

n/a

EQ-5D (no usable data), Fact-Leu (no usable data)

n/a

n/a

non-quantifiable

75

Brentuximab Vedotin

Oncologic diseases

OS

PFS, event-free survival, objective response rate, complete remission, decline B-symptoms, stem cell transplant rate

n/a

n/a

n/a

n/a

non-quantifiable

76

Decitabin

Oncologic diseases

OS

CR

n/a

EORTC QLQ-C30 (no valid data), EORTC QLQ-C30 (no valid data)

n/a

n/a

minor

77

Ruxolitinib [annulled]

Oncologic diseases

OS

Spleen volume reduction (MFSAF) version 2.0

EORTC QLQ-C30 (fatigue)

EORTC QLQ-C30 (quality of life), EORTC QLQ-C30, FACT-Lym (no valid data)

n/a

n/a

minor

78

Ivacaftor

Metabolic diseases

n/a

FEV (1%), BMI (inkl. Z-Wert), pulmonary exacerbation (PE)

CFQ-R (respiratory system, child and parents), EQ-5D

n/a

n/a

n/a

considerable

79

Pasireotid

Metabolic diseases

n/a

Proportion of responders, proportion of reducers, mUFC-basic value, blood pressure, LDL-cholesterol, weight

Beck-Depressions-Inventar

Cushing’s Quality of Life Questionnaires Questionnaire (CushingQoL)

n/a

n/a

minor

80

Tafamidis Meglumin

Other diseases

n/a

Neuropathy Impairment scale of the lower limb (NIS-LL), NIS-LL responder

n/a

Norfolk QOL-DN

n/a

n/a

minor

81

Pirfenidon

Respiratory diseases

n/a

n/a

n/a

n/a

n/a

n/a

non-quantifiable