Practical Systematic Literature Reviews for HEOR, Regulatory, HTA and Market Access

Systematic Literature Reviews (SLRs) are the highest level of evidence for value assessment, regulatory approvals and market access. However, conducting SLRs is an art and a science. An SLR requires a formal process and thoughtful design. The slides in this deck were presented at a workshop organized by Dr. Ozlem Topaloglu, PhD, MPH and Saurabh (Rob) Aggarwal, PhD of NOVEL Health Strategies.

NOVEL's experience of conducting SLRs includes SLRs for FDA (Dr. Topaloglu won many prestigious awards for her reviews), EMA (as part of regulatory submission), NICE (as part of HTA submission), Cochrane (Dr. Topaloglu is co-author of multiple Cochrane reviews) and for top journals such as Bone Marrow Transplant, Nature Reviews and Nature Biotechnology.

Transcript

1. Methods and Case Studies of SLRs for regulatory, market access, HTA and HEOR Speakers: Ozlem Topaloglu, PhD, MPH and Saurabh (Rob) Aggarwal, PhD NOVEL Health Strategies Contact: info@novelhealthstrategies.com Practical Systematic Literature Reviews
2. Contents ★ Art and Science of Systematic Literature Reviews (SLRs) ★ Insights from NOVEL Health Strategies Case Studies ★ Key Practical Considerations for Conducting SLRs ★ Examples of SLRs for FDA, EMA, NICE and HEOR ★ Trends in Systematic Review Publications by Big Pharma and Device ★ Appendix: Awards and Recognitions for NOVEL Health Strategies
3. Systematic Literature Reviews and Meta-Analyses are Highest Level of Evidence for All Stakeholders ➔ SLRs and meta-analyses are the highest level of evidence for decision making and value assessment by regulatory agencies, HTAs, payers and medical Guidelines ➔ Most agencies require SLRs and meta-analyses as part of the official submission process
4. NICE Guidance Says Evidence Should be Obtained from SLRs “Evidence on outcomes should be obtained from a systematic review, defined as systematically locating, including, appraising and synthesising the evidence to obtain a reliable and valid overview of the data” NICE UK Guidance
5. Process for Conducting Systematic Literature Reviews Hypothesis Generation Protocol Development Developing PICOs Design and Test Search Strategy Develop Master Database of all records De-Duplication and Manual Screening Data Extraction Analysis and Reporting of Results
6. Hypothesis Generation or Review Questions Examples of review questions: ❖ For people with IBS (irritable bowel syndrome), are antimuscarinics or smooth muscle relaxants effective compared with placebo or no treatment for the long-term control of IBS symptoms? Which is the most effective antispasmodic? ❖ Which first-line opioid maintenance treatments are effective and cost-effective in relieving pain in patients with advanced and progressive disease who require strong opioids? Source: https://www.nice.org.uk/process/pmg6/chapter/developing-review-questions-and-planning-the-systematic-review
7. Protocol Development (NICE Guidance) Component Description Review question The review question as agreed by the review team Objectives Short description; for example 'To estimate the effectiveness and cost effectiveness of…' or 'To estimate the diagnostic accuracy of…'. Criteria for considering studies for the review Using the PICO framework. Including the study designs selected. How the information will be searched The sources to be searched and any limits that will be applied to the search strategies; for example, publication date, study design, language. (Searches should not necessarily be restricted to RCTs.) The review strategy The methods that will be used to review the evidence, outlining exceptions and subgroups. Indicate if meta-analysis will be used and how it will be conducted.
8. Developing PICOs Population What is the target population for the review? Intervention Which interventions should be included and excluded? Comparator Which comparators will be included? Outcomes Which outcomes will be analyzed?
9. Designing and Testing Search Strategy
10. Problem with Search Filters
11. Two Databases to Search (Minimum)
12. Other Databases to Search
13. Conferences to Search (Varies depending upon indication)
14. Designing Data Extraction Forms
15. PRISMA Chart for Study Selection
16. PRISMA Flow Diagram is a Must “A flow diagram of the numbers of studies included and excluded at each stage should be provided using a validated statement for reporting systematic reviews and meta-analyses, such as the PRISMA flow diagram” NICE UK Guidance
17. Contents ★ Art and Science of Systematic Literature Reviews (SLRs) ★ Insights from NOVEL Health Strategies Case Studies ★ Key Practical Considerations for Conducting SLRs ★ Examples of SLRs for FDA, EMA, NICE and HEOR ★ Trends in Systematic Review Publications by Big Pharma and Device ★ Appendix: Awards and Recognitions for NOVEL Health Strategies
18. FDA SLR on Safety of Surgical Staplers https://www.fda.gov/media/126211/download
19. NICE UK SLR by Merck for Keytruda https://www.nice.org.uk/guidance/ta428/documents/committee-papers
20. ICER SLR on CAR-T Gene Therapies https://icer-review.org/wp-content/uploads/2017/07/ICER_CAR_T_Evidence_Report_021518.pdf
21. Canada CADTH SLR for CAR-T Therapies https://cadth.ca/sites/default/files/pdf/car-t/op0538-tisagenlecleucel-clinical-report_jan2019.pdf
22. ★ Art and Science of Systematic Literature Reviews (SLRs) ★ Insights from NOVEL Health Strategies Case Studies ★ Key Practical Considerations for Conducting SLRs ★ Examples of SLRs for FDA, EMA, NICE and HEOR ★ Trends in Systematic Review Publications by Big Pharma and Device ★ Appendix: Awards and Recognitions for NOVEL Health Strategies Contents
23. Top 10 Pharma published 300 Systematic Reviews in 2006-2019, with Pfizer as the number one author Systematic Reviews Published by Big Pharma
24. Pfizer Published 20 SLRs on Efficacy (Full Text) 1. Economic Impact of Etanercept in Patients with Psoriasis and Psoriatic Arthritis in Spain: A Systematic Review 2. Obstetric venous thromboembolism: a systematic review of dalteparin and pregnancy 3. Systematic Review and Meta-analysis of Short- versus Long-Acting Granulocyte Colony-Stimulating Factors for Reduction of Chemotherapy-Induced Febrile Neutropenia 4. Efficacy of Monotherapy with Biologics and JAK Inhibitors for the Treatment of Rheumatoid Arthritis: A Systematic Review 5. A quick scoping review of efficacy, safety, economic, and health-related quality-of-life outcomes of short- and long-acting erythropoiesis-stimulating agents in the treatment of chemotherapy-induced anemia and chronic kidney disease anemia 6. A systematic review of network meta-analyses among patients with nonvalvular atrial fibrillation: A comparison of efficacy and safety following treatment with direct oral anticoagulants 7. Disease-modifying effects of COX-2 selective inhibitors and non-selective NSAIDs in osteoarthritis: a systematic review 8. Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review 9. Effects of etanercept on the patient-perceived results (PROs) in patients with moderate-to-severe plaque psoriasis: systematic review of the literature and meta-analysis 10. The comparative immunogenicity of biologic therapy and its clinical relevance in psoriatic arthritis: a systematic review of the literature 11. Down-titration of biologics for the treatment of rheumatoid arthritis: a systematic literature review 12. Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer 13. Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review 14. Quantitative Evaluations of Time-Course and Treatment Effects of Systemic Agents for Psoriasis: A Model-Based Meta-Analysis 15. Biosimilars for the Treatment of Cancer: A Systematic Review of Published Evidence 16. Factors Related to the Glucose-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis Focusing on Ethnicity and Study Regions 17. An appraisal of meta-analysis guidelines: how do they relate to safety outcomes? 18. Optimal Treatment for Complicated Intra-abdominal Infections in the Era of Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Therapy With Metronidazole 19. Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis 20. Efficacy of PPV23 in Preventing Pneumococcal Pneumonia in Adults at Increased Risk--A Systematic Review and Meta-Analysis
25. Pfizer Published 12 SLRs on Burden of Illness (Full Text) 1. Disease burden and treatment challenges of psoriatic arthritis in Africa and the Middle East 2. Epidemiological burden of meningococcal disease in Latin America: A systematic literature review 3. Global and Regional Burden of Hospital Admissions for Pneumonia in Older Adults: A Systematic Review and Meta-Analysis 4. Surgical site infection in elective clean and clean-contaminated surgeries in developing countries 5. Targeted literature review of the humanistic and economic burden of adult growth hormone deficiency 6. Patient impact and economic burden of mild-to-moderate atopic dermatitis 7. Burden of clinical infections due to S. pneumoniae during Hajj: A systematic review 8. Burden of Ulcerative Colitis on Functioning and Well-being: A Systematic Literature Review of the SF-36® Health Survey 9. The full benefits of adult pneumococcal vaccination: A systematic review 10. Restoring function in major depressive disorder: A systematic review 11. Biosimilars for the Treatment of Cancer: A Systematic Review of Published Evidence 12. A systematic review of the burden of vaccine preventable pneumococcal disease in UK adults
26. Novartis Published 11 SLRs on Efficacy (Full Text) 1. Barriers and facilitators to shared decision-making in oncology: a systematic review of the literature 2. Secukinumab for psoriatic arthritis: comparative effectiveness versus licensed biologics/apremilast: a network meta-analysis 3. Safety and efficacy of lithium in children and adolescents: A systematic review in bipolar illness 4. Patient-reported outcomes in European spondyloarthritis patients: a systematic review of the literature 5. LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis 6. The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in nAMD: Systematic Review and Network Meta-Analysis 7. Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis 8. Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and meta-analysis of randomized trials 9. Clear or almost clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic review and meta-analysis 10. Clinical trials for authorized biosimilars in the European Union: a systematic review 11. Effect of Telbivudine Versus Other Nucleos(t)ide Analogs on HBeAg Seroconversion and Other Outcomes in Patients with Chronic Hepatitis B: A Network Meta-Analysis
27. Novartis Published 7 SLRs on Burden of Illness (Full Text) 1. Systematic literature review on the economic, humanistic, and societal burden of heart failure in children and adolescents 2. Evidence supporting wound care end points relevant to clinical practice and patients' lives. Part 2. Literature survey 3. Gender-specific estimates of COPD prevalence: a systematic review and meta-analysis 4. Effectiveness of omalizumab in adolescent and adult patients with chronic idiopathic/spontaneous urticaria: a systematic review of 'real-world' evidence 5. A Systematic Review of the Effect of Cancer Treatment on Work Productivity of Patients and Caregivers 6. A Systematic Review of the Incidence, Risk Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease in Africa (1966 to 2014) 7. Cost of severe asthma in Brazil-systematic review
28. Novartis Published 5 SLRs on Quality of Life (Full Text) 1. Omalizumab and long-term quality of life outcomes in patients with moderate-to-severe allergic asthma: a systematic review 2. Measurement and evaluation of quality of life and well-being in individuals having or having had fertility problems: a systematic review 3. Measuring quality of life of people with predementia and dementia and their caregivers: a systematic review protocol 4. Clear or almost clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic review and meta-analysis 5. Health-related quality of life in patients with psoriasis: a systematic review of the European literature
29. ★ Art and Science of Systematic Literature Reviews (SLRs) ★ Insights from NOVEL Health Strategies Case Studies ★ Key Practical Considerations for Conducting SLRs ★ Examples of SLRs for FDA, EMA, NICE and HEOR ★ Trends in Systematic Review Publications by Big Pharma and Device ★ Appendix: Awards and Recognitions for NOVEL Health Strategies Contents
30. Awards and Recognitions Celebrating Our 9th Year (2011-2019) NOVEL Health Strategies Ozlem Topaloglu, PhD, MPH Saurabh Aggarwal, PhD Contact: info@novelhealthstrategies.com
31. Ozlem Topaloglu, PhD, MPH Senior Director, NOVEL Health Strategies Previous experience: FDA, CMS, Parexel, Tufts CE Registry, Johns Hopkins School of Medicine
32. Outstanding Service Award
33. Special Recognition Award by Division of Epidemiology
34. Excellence in Premarket Team Award
35. Essential Piece Award by Division of Epidemiology
36. Special Recognition Award
37. Reward and Recognition
38. Special Recognition Award
39. Excellence in Premarket Team Award
40. Excellence in Premarket Team Award
41. Outstanding Service Award
42. Excellence in Premarket Team Award
43. Saurabh (Rob) Aggarwal, PhD Principal and Co-Founder, NOVEL Health Strategies Previous experience: Parexel, IMS, Sanford Bernstein, Johns Hopkins University
44. 2 Platinum Medals Every year AMCP awards 5-6 Platinum Medals to Select Studies. NOVEL Health Strategies Won Platinum Medals Two Times
45. Platinum Medal from AMCP
46. Platinum Medal from AMCP
47. Nomination for ‘Best Research Award’
48. Nomination for ‘Best Research Award’
49. Nomination for ‘Best Research Award’
50. Nomination for ‘Best Research Award’
51. 158 Peer-Reviewed Studies NOVEL Health Strategies has authored 150+ studies that were presented in major conferences and/or published in top journals https://scholar.google.com/scholar?q=”NOVEL Health Strategies”
52. 12 Publications in Nature Journals (30+ Impact Factor) NOVEL Health Strategies is the only team to have authored 10+ publications in the highest impact journals.
53. Contact info: Ozlem Topaloglu, PhD, MPH Saurabh (Rob) Aggarwal, PhD info@novelhealthstrategies.com www.novelhealthstrategies.com Lets collaborate