Commissioning and using systematic reviews: a decision-maker’s perspective Kalipso Chalkidou NICE, UK
Topic Selection • Independent horizon scanning; web-based suggestions; field consultants; regular evidence review by NICE information teams • Pharma sharing its pipelines, part of pricing reforms of 2009 • Multi-stakeholder panels led by top UK clinician sift based on criteria (health and budget impact, variation…) • Final ratification by Department of Health but responsibility gradually passed on to NICE to speed up process
Example of topic referral • On 18 September 2007 the Department of Health formally requested that the National Institute for Health and Clinical Excellence prepare a clinical guideline on: “The rehabilitation of adults after a period of critical illness requiring a stay on ITU.”
Examples of stakeholders expressing an interest • British Association of Critical Care • Royal College of Nursing • British Society of Rehabilitation Medicine • Bradford Teaching Hospitals NHS Foundation Trust • Royal College of Speech and Language Therapists • GlaxoSmithKline UK • BUPA • Department for Communities and Local Government • Department of Health • Long-term Conditions Alliance • …
Scope workshop and consultation • 55 people registered to attend the scoping workshop including nurses, psychotherapists, ICU specialists, academics, lay people/carers, industry reps… • 23 stakeholders commented on the draft scope… • “The College believes the draft scope has been well prepared and reflects the views of the workshop held in Manchester on March 28th.” The Royal College of Physicians • “It would be helpful if the section that relates to the settings covered by this guideline, it is made explicit that all settings where psychological rehabilitation is delivered are to be included - this is hinted at but needs to be clearly stated” British Psychological Society • Scope amended to include general medical/surgical setting where post-ICU care is offered
Bringing the evidence together • £££: Department of Health and NICE • The experts: universities and professional associations; NICE Information Specialists and Short Guideline technical teams • Industry: Single Technology Appraisal increasingly relying on manufacturers • Independent review commissioned by academic group • Early in the process, manufacturer more likely to hold confidential data • More timely and more efficient way of evaluation • But…may compromise independence?
Biases… (Miners et al, BMJ 2005)
Evidence hierachies Experiment, observation and mathematics – individually and collectively – have a crucial role to play in providing the evidential basis for modern therapeutics. Hierarchies of evidence should be replaced by accepting – indeed embracing – a diversity of approaches. This is not a plea to abandon RCTs and replace them with observational studies. Rather, it is a plea to investigators to continue to develop and improve their methodologies; to decision makers to avoid adopting entrenched positions about the nature of evidence; and for both to accept that the interpretation of evidence requires judgement.” M Rawlins, 2008 Harveian Oration • Critical appraisal of existing evidence • Systematic reviews and meta-analyses of RCTs and non-experimental studies – encourage individual patient level data analysis; indirect/mixed treatment comparisons • Registries and claims data to establish epidemiological characteristics of UK population and baselines • Expert opinion
Overview of the GRADE approach • Assessment of the quality of the evidence (for each outcome) • Assessment of balance between desirable and undesirable outcomes • Judgement about the strength of the recommendation • Key differences from previous NICE method • Separate quality assessment for each outcome • Separates out judgements about the quality of the evidence from judgements about the strength of the recommendation • Using a modified version of GRADE *Grade Working Group. CMAJ 2003, BMJ 2004, BMC 2004, BMC 2005
A case study: DES vs BMS • 25 RCTs for comparative effectiveness/safety • Meta-analysis pooling results from over 7000 trial participants • Multiple outcomes: mortality, acute MI, revascularisation, composite event, angiographic binary restenosis, late luminal loss • 10 peer reviewed economic evaluations; 3 manufacturers’ and 1 3rd party model • 2 market price surveys: >20 hospital trusts • Hundreds of submissions by professional bodies; researchers; patients; industry • Expert testimonies patients and physicians • UK registry data: baseline risk/re-intervention rates
Patients’ views matterCase study - Psoriasis Clinical research told us the amount of psoriasis was what most affected the quality of life. Patients told us that the location of the flare-up (e.g. face or joints) was more significant.
Peer review – quality assurance • Independent systematic reviews and economic analyses of published literature to inform process • Public consultation and audit trail for responding to comments • In-depth expert statistical and health economic review through the Health Technology Assessment programme and peer reviewed publication • Independent committee overseeing adherence to process and response to stakeholder comments Guideline Review Panels • Methods consistently applied and regularly updated • Transparency of process
Guideline process Stakeholder involvement Topic referred to NICE* Scoping* Development Draft guideline* Pre–Publication check* Publication* * Published on NICE web site Dissemination
NICE Code of practice for Declaring Interests (April 2007) • Applies to: • NICE employees, NICE Chairman and non-executive board members • Chairs and members of the advisory bodies to NICE, including GDG chairs and GDG members • Expert advisors attending GDG meeting • Employees of organisations contracted by NICE (including staff at NCCs)
Let us not forget the importance of prospective evidence generation • “Although thousands of medical studies are completed every year, most have relatively limited goals. They often carefully select patients who have few medical problems other than the one under study, making it easier to get one clear result. They may not look at effects over the long term, assuming that if a treatment helps initially, patients will be better off. …Such limited studies, while they can have value, may no longer be enough, particularly when care has become so expensive and real evidence more crucial.” • New York Times, November 2008