Table 2 Evidence available at time of pre-reimbursement assessment in Austria and at time of FDA approval, levels of evidence

1. Percutaneous pulmonary valve implantation for right ventricular outflow tract dysfunction in patients with congenital heart defects

Melody™

NB 2006

FDA 2010

4

2008 [14]: 4 retrospective + prospective case series, 8–68 pts

5

HDE approval based on 1 prospective case series 99 pts, requirement of 2 post-approval studies with 5y FU [13]

2. Percutaneous aortic valve replacement/ TAVI

CoreValve^®

2007

FDA 2014

2

SAPIEN XT™

2008 [16]: retrospective + prospective 10 case series, 8–86 pts

5

CoreValve^® PMA approval based on 1 RCT, 656 pts [15] (CoreValve U.S. Pivotal Trial), requirement for post-approval study on extreme risk patients.

2009 [18]: see 2008 + 4 case series, 12–646 pts 2010 [19]: see 2008 + 2009 + 6 cohort studies (registries), 4 HTAs

4

4

SAPIEN XT™ PMA approval based on 1 RCT, 560 pts [17] (PARTNER II), requirement for post-approval study on inoperable patients cohort

2

2

2011 [20]: see 2008 + 2009 + 2010 + 1 RCT, 358 pts (PARTNER I)

3. Cardiac contractility modulation (CCM) for heart failure

Optimizer™ III/IV

NB 2007

-

-

2008 [21]: 2 RCTs, 49/164 pts (FIX-HF-4/ OPTIMIZER) +2 case series 13/25 pts)

2

IDE Status: Optimizer™ III Optimizer™ III/IV Trial FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER^®) ongoing

2009 [22]: see 2008 + 1 RCT-Protokoll, 428 pts (FIX-HF-5/ OPTIMIZER)

2

2010 [23]: see 2009

2

4. Percutaneous transluminal angioplasty (PTA) of periphery arteries with drug-eluting balloon (DEB)

In.Pact™ Amphirion + Admiral

NB 2009/11/12/13

FDA 2014

1 + 3

2013 [25]: 4 RCTs, 50–102 pts(2 × In.Pact™ DEBELLUM, PACIFIER, 2 × Cotovance™ THUNDER, FemPac) +2 cohort studies (registries: In.Pact™ Admiral, In.Pact™ Amphirion)

1-2

Lutonix DCB^® PMA based on LEVANT 2 RCT, 476 pts + LEVANT 2 registry, 657 pts. [24]

Lutonix DCB^®

Cotavance™

Advance 18 PTX^®

IDE Status: In.Pact™ Admiral based on SFA I and SFA II RCT, 331 pts

LEGflow™

No IDE Status: Cotavance™ (IDE suspended), Advance 18 PTX (only EU), LEGflow™ (RAPID trial EU),Freeway™ (only EU)

ELUTAX SV™

Freeway™

5. Percutaneous transluminal coronary angioplasty (PTCA) with drug-eluting balloon (DEB)

Dior^® PCBr

NB 2007/09/11

-

-

SeQuent^® DCB In.Pact™ Admiral

2009 [26]: 2 RCTs, 52/108 pts (2x Cotavance™ PACCOCATH I, II)

1-2

IDE Status: In.Pact™ Admiral/ Medtronic based on SFA I and SFA II RCT, 331 pts

Cotavance™

2013 [27]: 5 RCTs for ISR, 50–271 pts (4 × SeQuent^® PEPCAD II-IV + 1 × Cotavance™ PACCOCATH II FU) +1 RCT for SVD, 60 pts (Dior^® PICCOLETO) +1 RCT for de-novo lesions, 84 pts (SeQuent^®)

1-2

No IDE Status :Dior^® PCB (only EU), SeQuent^® DCB: (only EU), Cotavance™ (IDE suspended)

6. Percutaneous repair of mitral regurgitation with the MitraClip

MitraClip^®/Abbott

NB 2008

4

FDA 2013

2010 [28]: prospective case series (EVEREST I/II), 107 pts 2012 [30]: 2010 + 10 case series +1 RCT, 279 pts (EVEREST II)

2

MitraClip^® PMA approval based on EVEREST II RCT, 279 pts., EVEREST II high-risk registry (EVEREST II HRR), 78 pts and EVEREST II Cont. access registry (REALISM HR), 853 pts [29], requirement of 2 post-approval studies (registries)

2 + 3

7. Renal denervation

Symplicity™ RDN/Medtronic

NB 2008

-

-

2011 [31]: 1 prospective case series (SYMPLICITY HTN-1), 50 pts; 1 RCT, 106 pts. (SYMPLICITY HTN-2)

4, 2

IDE Status: IDE approval study SYMPLICITY HTN-3, 535 pts. failed; 2014 approval process suspended [32], IDE approval study SYMPLICITY HTN-4 ongoing

4, 2

2012 [33]: 2011+ 1 case series, 153 pts. (FU SYMPLICITY HTN-1)

8. Endovascular repair of aortic aneurysms

Zenith^® Fenestrated AAA Endovascular Graft

NB 2005/13

FDA 2012

4

2013 [34]: 2 HTAs +4 SR based on 1 (non-randomised) controlled study, 187 pts +7-20 case series, 196–368 pts

3

Zenith^® Fenestrated AAA Endovascular Graft PMA approval based on 1 (historic case-) controlled study, 42 pts [35], requirement of a long-term follow-up study.

Ventana™ Fenestrated System

IDE Status: Ventana™ Fenestrated System

9. Percutaneous transluminal angioplasty (PTA) with drug-eluting stents in peripheral arterial disease, upper limb and thorax

Femoropopliteal:

NB 2009/ 12/13

1 + 2

1 + 2

FDA 2012 Zilver^® PTX^® PMA approval based on Zilver PTX randomised study, 479 pts. [37]

2

Zilver^® PTX^® Innova™

2014 [36]: Femoropopliteal

S.M.A.R.T.^®

3 RCTs, 36–479 pts (1 × Zilver^® PTX study, 2 × S.M.A.R.T.^® SCIROCCO I + II) +1 non-randomised CTs, 93 pts (Zilver^®) +1 case series, 787 pts.

IDE Status: S.M.A.R.T.^® Vascular Stent System No IDE Status: Innova™ Peripheral Vascular DES System (MAJESTIC in Australia, New Zealand, EU); XIENCE^® Prime BTK;

Infrapopliteal:

XIENCE^® Prime BTK

Infrapopliteal

Yukon^®; PROMUS Element™PlusDES BTK; CYPHER^® Select (discontinued to be marketed)

Yukon^®

4 RCTs, 50–200 pts (1 × XIENCE^® DESTINY, 1 × Yukon^® YUKON-BTK, 2× CYPHER^® ACHILLES) +3 non-randomised CTs, 58–103 pts +3 case series, 114–146 pts (all CYPHER^® Select)

PROMUS Element™PlusDES BTK

CYPHER^® Select

10. Percutaneous left atrial appendage closure for the prevention of thromboembolic events in patients with atrial fibrillation

Watchman^® LAA Closure Technology

NB 2005/08/12/13

4 + 5

-

-

2011 [38]: 4 case series, 64–180 pts; 1 cohort study/ registry, 73 pts; 1 RCT, 542 pts (Watchman^® PROTECT AF)

2009: Watchman^® LAA Closure Technology PMA approval based on RCT, 707 pts (PROTECT AF) declined[39]

AMPLATZER™ Cardiac Plug

3 + 2

Coherex WaveCrest™ LAA Occlusion System

2014 [40]: 2011 + 3 FU studies of PROTECT AF +

IDE Status: Watchman^® LAA Closure, re-application with RCT PREVAIL, 407 pts; AMPLATZER™ Cardiac Plug (RESPECT), 980 pts

3 case series, 52–86 pts +1 cohort study/ registry, n/a; 2 prospective CTs, 80/150 pts