Patient Reported Outcomes (PROs) play a pivotal role in shaping Health Technology Assessments (HTAs) and market access decisions for pharmaceuticals, biotech’s, and medical technologies. These outcomes provide valuable insights into the patient experience, treatment efficacy, and quality of life, complementing traditional clinical endpoints and economic evaluations. By incorporating PRO measures into clinical trials and submissions, companies can enhance the value proposition of their health technologies and demonstrate their impact on patients’ lives.
Key Points:
1. Strategic Use of PRO Data: Companies strategically incorporate PRO measures into clinical trials and submissions to address gaps in evidence for HTAs and to achieve commercial objectives. PRO data are particularly valuable in post-approval effectiveness studies were randomized controlled trial (RCT) data may be insufficient.
2. Competitive Positioning: Examples such as Dupixent for Atopic Dermatitis, Humira for Rheumatoid Arthritis, and Gilenya for Multiple Sclerosis demonstrate how PRO data have significantly improved the competitive position of products in the market. These examples highlight the importance of PROs in differentiating therapies, showcasing patient-centric outcomes, and contributing to market success.
3. Expedited Approvals: PRO data have facilitated expedited approvals for products like Kalydeco for Cystic Fibrosis and Spinraza for Spinal Muscular Atrophy. These examples illustrate how compelling PRO evidence can lead to priority reviews and rapid approvals by regulatory agencies, providing patients with access to innovative therapies more quickly.
4. Value in HTA Submissions: PROs bring several benefits to HTA submissions, including comprehensive evaluation, support for comparative effectiveness research, enhanced value proposition, and increased patient engagement. In markets like Germany, PROs are expected to be included in HTA submissions and can positively influence reimbursement decisions.
Real-World Examples:
1. Dupixent (dupilumab) for Atopic Dermatitis:
– Company: Sanofi and Regeneron
– PRO Impact Simpson, E. L., et al. (2016). “Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.” New England Journal of Medicine, 375(24), 2335-2348.
2. Humira (adalimumab) for Rheumatoid Arthritis:
– Company: AbbVie
– PRO Impact: Keystone, E. C., et al. (2004). “Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumour necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial.” Arthritis & Rheumatology, 50(5), 1400-1411.
3. Gilenya (fingolimod) for Multiple Sclerosis:
– Company Novartis
– PRO Impact: Cohan, S., et al. (2017). “Effectiveness of fingolimod in patients with multiple sclerosis switched directly from injectable therapies: results of the EPOC trial.” BMC Neurology, 17(1), 143.
4. Kalydeco (ivacaftor) for Cystic Fibrosis:
– Company: Vertex Pharmaceuticals
– PRO Impact: Ramsey, B. W., et al. (2011). “A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.” New England Journal of Medicine, 365(18), 1663-1672.
5. Spinraza (nusinersen) for Spinal Muscular Atrophy:
– Company: Biogen
– PRO Impact: Finkel, R. S., et al. (2017). “Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy.” New England Journal of Medicine, 377(18), 1723-1732.
6. Entresto (sacubitril/valsartan) for Heart Failure:
– Company: Novartis
– PRO Impact: (Reference needed)
7. Keytruda (pembrolizumab) for Cancer Immunotherapy:
– Company: Merck & Co.
– PRO Impact (Reference needed)
8. Harvoni (ledipasvir/sofosbuvir) for Hepatitis C:
– Company Gilead Sciences
– PRO Impact: (Reference needed)
9. Ocrevus (ocrelizumab) for Multiple Sclerosis:
– Company: Genentech (a member of the Roche Group)
– PRO Impact: (Reference needed)
10. Orkambi (lumacaftor/ivacaftor) for Cystic Fibrosis:
– Company Vertex Pharmaceuticals
– PRO Impact: (Reference needed)
11. Taltz (ixekizumab) for Psoriasis:
– Company: Eli Lilly and Company
– PRO Impact: (Reference needed)
12. Lenvima (lenvatinib) for Thyroid Cancer:
– Company: Eisai Co., Ltd.
– PRO Impact: (Reference needed)
13. Imbruvica (ibrutinib) for Chronic Lymphocytic Leukemia (CLL):
– Company: Janssen Pharmaceuticals and Pharmacyclics LLC (an AbbVie company)
– PRO Impact: (Reference needed)
14. Entresto (sacubitril/valsartan) for Heart Failure with Reduced Ejection Fraction (HFrEF):
– Company: Novartis
– PRO Impact: (Reference needed)
15. Kadcyla (trastuzumab emtansine) for HER2-Positive Breast Cancer:
– Company: Genentech (a member of the Roche Group)
– PRO Impact: (Reference needed)
16. Tecfidera (dimethyl fumarate) for Multiple Sclerosis (MS):
Company: Biogen
PRO Impact: (Reference needed)
Conclusion:
In conclusion, PROs play a crucial role in shaping HTA submissions and market access decisions, providing valuable insights into treatment outcomes, patient preferences, and quality of life. Companies that incorporate PRO measures into their clinical development programs and submissions can strengthen the evidence base for their products, differentiate themselves in the market, and ultimately improve patient access to innovative therapies.
References:
- Simpson, E. L., et al. (2016). “Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.” New England Journal of Medicine, 375(24), 2335-2348.
- Keystone, E. C., et al. (2004). “Radiographic, clinical, and functional outcomes of treatment with adalimumab in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial.” Arthritis & Rheumatology, 50(5), 1400-1411.
- Cohan, S., et al. (2017). “Effectiveness of fingolimod in patients with multiple sclerosis switched directly from injectable therapies: results of the EPOC trial.” BMC Neurology, 17(1), 143.
- Ramsey, B. W., et al. (2011). “A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.” New England Journal of Medicine, 365(18), 1663-1672.
- Finkel, R. S., et al. (2017). “Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy.” New England Journal of Medicine, 377(18), 1723-1732.
- McMurray, J. J. V., et al. (2014). “Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure.” New England Journal of Medicine, 371, 993-1004.
- Ribas, A., et al. (2015). “Pembrolizumab (Keytruda) for the treatment of advanced melanoma.” New England Journal of Medicine, 372, 320-330.
- Younossi, Z. M., et al. (2016). “Sustained virologic response and patient-reported outcomes in patients with chronic hepatitis C and advanced fibrosis.” Liver International, 36(1), 42-49.
- Hauser, S. L., et al. (2017). “Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.” New England Journal of Medicine, 376, 221-234.
- Wainwright, C. E., et al. (2015). “Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR.” New England Journal of Medicine, 373, 220-231.
- Griffiths, C. E., et al. (2015). “Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.” The Lancet, 386, 541-551.
- Schlumberger, M., et al. (2015). “Lenvatinib versus placebo in radioiodine-refractory thyroid cancer.” New England Journal of Medicine, 372, 621-630.
- Burger, J. A., et al. (2015). “Ibrutinib as initial therapy for patients with chronic lymphocytic leukaemia.” New England Journal of Medicine, 373, 2425-2437.
- Verma, S., et al. (2012). “Trastuzumab emtansine for HER2-positive advanced breast cancer.” New England Journal of Medicine, 367, 1783-1791.
- Gold, R., et al. (2012). “Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.” New England Journal of Medicine, 367, 1098-1107. Entresto (sacubitril/valsartan) for Heart Failure