in compiling the clinical evidence for a supportive device the sponsor should ensure that a clinician who is an expert in the field and experienced in the use of the device compiles and critiques all the clinical data that informs on the safety and performance of the device the clinical expert must review and endorse the CER containing the clinical evidence to demonstrate that the evidence the requirements of the applicable EPs and the device is safe and performs as intended. Defining joint prostheses This guidance document describes joint prostheses as an implantable medical device, irrespective of its configuration, that is intended by the manufacturer to replace in full or in part a section of the joint. From the MD Regulations— joint replacement medical device means an implantable medical device: that is intended by the manufacturer to operate (either or together with one or more other implantable medical devices) as a replacement (in whole or in part) for the shoulder joint, hip joint or knee joint; and that (either or together with one or more other implantable medical devices): replaces or substitutes for the articulating surface of a shoulder hip joint or knee joint (in whole or in part); or provides primary fixation to the bone for the replacement articulating surface; or connects directly or indirectly with an implantable medical device that has a function mentioned in subparagraph (i) or (ii) and operates as an intrinsic element of the joint replacement; but does not include an ancillary medical device. ancillary medical device means an implantable medical device that: consists of screws, plates or wedges; or is intended by the manufacturer to be used to: provide stability for an implantable medical device that is intended to (either alone or together with one or more other implantable medical devices) replace the shoulder joint, hip joint or knee joint; or provide bone substitution in relation to, or additional fixation for, any such device; or otherwise assist any such device; where the individual requirements of a patient make it appropriate to do so. Joint prostheses can consist of either a monoblock or modular design. There are practical advantages to modular designs as they allow tailoring of the prosthesis to the patient’s anatomy. However, modular devices with multiple components are more complex and may have a
explant all stroke (disabling and non-disabling) life threatening bleeding (note: bleeding should be classified as either ‘all haemorrhage’ or haemorrhage’) acute kidney injury (stage 2 or 3, including renal replacement therapy) peri-procedural myocardial infarction endocarditis vascular complication coronary obstruction requiring intervention valve-related dysfunction (note: valve regurgitation should be reported as ‘all paravalvular leaks’ and ‘major paravalvular leaks’) In addition, it is recommended the following outcomes be reported after 30 days: mortality all stroke (disabling and non-disabling) hospitalisation for symptoms or worsening congestive heart failure a quality of life measure e.g. the New York Heart Association Classification (NYHA) or the Minnesota Living with Heart Failure Questionnaire (MLHF) prosthetic valve endocarditis prosthetic valve thrombosis bleeding, unless unrelated to valve therapy (e.g. trauma) (note: bleeding should be classified as either ‘all haemorrhage’ or ‘major haemorrhage’ ‘anticoagulant-related haemorrhage’ reoperation thromboembolic events (e.g. stroke) structural valve deterioration non-structural valve dysfunction/valve related dysfunction (note: valve regurgitation should be reported as ‘all paravalvular leaks’ and ‘major paravalvular leaks’ and it should be noted if the dysfunction required a repeat At one year the following should be reported: Structural valve deterioration Thromboembolism (Major, reversible ischemic neurological deficit (RIND)) Valve thrombosis Anticoagulant-related haemorrhage Prosthetic valve endocarditis Non-structural valve dysfunction/paravalvular leak Re-operation
Characteristics of clinical studies of CV flow implants . Study characteristics extracted from systematic reviews and primary research reports on the safety and performance of selected CV flow implants Characteristics of included studies Arterial stents: Carotid (6 SRs) Coronary(6 SRs) Peripheral (5 SRs) Implants for AAA repair (4 SRs) xxxviii , & (1 retrospective comparative cohort) Implants for PDA repair (1 SR) & (1 retrospective cohort study) IVC filters (2 SRs) & (1 RCT) Carotid Coronary Peripheral Number of included studies per SR 11 to 41 10 to 28 4 to 14 5 to 32 7 2 and 8 Dominant design of included studies 3 SRs were limited to RCTs; 3 included a mix of MAs, RCTs, cohort studies, case series & registry studies 5 SRs were limited to RCTs; 1 included RCTs & observational studies 3 SRs were limited to RCTs; 1 included SRs & RCTs; 1 included RCTs & case series 2 SRs were limited to RCTs; 1 included RCTs & registries; 1 included RCTs, observational cohort studies & registries SR:23 All Level IV Primary study:22 Level IV SRs: Levels II-IV RCT=Level II
Sample size (range) for included studies 3 SRs with RCTs: total enrolled = 4,796 to 7,572 patients 3 SRs with various study designs: total enrolled = up to 575,556 5 SRs with RCTs: total enrolled = 6,298 to 14,740 patients 1 SR with RCTs and observational studies: total enrolled = 10,447 3 SRs with RCTs: enrolled = 627 to 1,387 patients 1 SR with SRs and RCTs; enrolled = unclear 1 SR with RCTs and case series: total enrolled = 1,628 2 SRs with RCTs: total enrolled = 1,594 to 3,194 patients 1 SR with RCTs & registries; enrolled = 52,220 patients 1 SR with RCTs, observational studies & registries: total enrolled = 72,114 Primary study: total enrolled = 2,198 SR 2014:xlv n=259 patients in device group; n=551 in control group Primary study:xlvi Level III-2 retrospective cohort with concurrent controls; n=51 in device group; n=130 in control group SR 2010:xlvii 2 RCTs of 129 and 400 patients (division between arms NR) SR 2014:xlviii n=432 in filter groups; n=4160 in historical control groups RCT 2012:xlix total n=141 (70 in device group, 71 in control group) Reported comparisons Carotid artery stenting vs. endarterectomy (one study also included medical therapy) 4 assessed DES versus BMS; 2 assessed DES versus BMS or another type of DES Balloon angioplasty with stents (BMS or DES) versus balloon angioplasty alone (one compared BMS versus DES) Primarily EVAR versus open repair; also EVAR versus watchful waiting in candidates deemed not fit for surgery Implanted device versus surgical closure IVC filter versus no filter
Quality of included evidence as reported 2 SRs did not report quality assessment; 1 developed a custom tool but did not report results; 3 used a tool developed by the Cochrane Collaboration and risk of bias generally low 1 SR did not report quality assessment; 1 developed a custom tool but did not report results; the other 4 used various tools and determined studies were generally high quality with low risk of bias All 5 SRs assessed study quality using a variety of tools (e.g., Cochrane Collaboration, Jadad, custom); quality was generally assessed as moderate to high SRs assessed via Jadad or Cochrane Collaboration tool. Other study types used NOS. RCT quality usually high; others low to moderate SR: With the NOS, assessed studies as having low-risk bias; funnel plot for primary outcome showed no obvious publication bias SR 2010:xlvii With D&B, assessed studies as low quality SR 2014:xlviii With the Jadad scale, assessed studies as scoring 2/5 & 3/5 (low) Patient From 1 to 5 years Generally 3 to 5 years 6 months to 8 generally months From post-op course in hospital up to 9.1 SR: 6 months Primary study: 24 months SR 2010:xlvii NR SR 2014:xlviii 34 days to 8 years RCT 2012: 15 (± SD 2) months SD=Standard deviation; SR=Systematic review; RCT=randomized controlled trial KEY: AAA=Abdominal aortic aneurysm; BMS=Bare metal stents; D&B=Downs & Black; DES=Drug eluting stents; EVAR=endovascular aneurysm repair; IVC=Inferior vena cava; MA=Meta-analysis; NOS=Newcastle-Ottawa scale; NR=not reported; PDA=Patent ductus trial;
Characteristics of clinical studies on heart valve prostheses . Summary of study characteristics of six systematic reviews on surgical aortic valve replacement identified in a health technology assessment Review Design of included studies Numbers of studies and patients Follow-up Comparison Kassai et al 2000 RCTs 3 studies (2 in adults) 1,229 patients (1,011 adult) Mean of 11–12 years for adults Aortic and/or mitral: mechanical vs. bioprosthetic Kunadian et al 2007 RCTs 11 studies 919 patients NR Aortic: Stented vs. non-stented bioprosthetic Lund and Bland, 2006 Observational 32 articles describing 38 case series 17,439 patients Mean 6.4 years for mechanical (range, 3.9 to 10.8) and 5.3 years (2.6 to 10.1 for bioprosthetic) Aortic: Mechanical vs. bioprosthetic Puvimanasghe et al 2004 Puvimanasinghe et al 2003 Observational 22 studies 13,281 patients Total follow-up in patient-years was 25,726 for St Jude mechanical and 54,151 for porcine bioprosthesis Aortic: St. Jude mechanical vs. porcine bioprosthetic Puvimanasinghe et al 2006 Observational 13 studies 6,481 patients 18 years for pericardial valves and up to 20 years for porcine supraanular valves Aortic: pericardial aortic vs. bioprosthetic Rizzoli et al 2004 Observational 11 studies 1,160 patients Mean duration: 6.8 years Tricuspid: Bioprosthetic vs. mechanical valves NR: not reported
Function scores Pelvic Prolapse Quantification System (POP-Q) Incontinence Impact Questionnaire prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) Patient Global Impression of Change (PGIC) Pelvic Floor Distress Inventory (PFDI-20) Pelvic Floor Impact Questionnaire (PFIQ-7) Surgical Satisfaction Questionnaire (SSQ) Existence of CSF leakage Quality of Life (QoL) scores SF-36 SHS SF-12 EuroQol EQ-5D