Access to Prescription Drugs: What Every Patient Should Know

1. Access to Prescription Drugs: What Every Patient Should Know DAY 1: About Drug Development Durhane Wong-Rieger, PhD Consumer Advocare Network

2. S1: New Drug for Previously Untreated Condition • Background of Disease • Rare Condition, genetic condition affecting fewer than 1 in 30,000 persons (1,000 Canadians) • Progressive disorder (continues to get worse) • Only previous treatment was symptom management (pain, gastrointestinal, kidney failure, risk of heart disease and stroke) HTA Drug Development

3. S1: New Drug for Previously Untreated Condition • What questions should you ask before considering the drug • What “evidence” would you want before taking the drug? • As a drug developer, how would you “generate” that evidence? HTA Drug Development

4. S1: New Drug for Previously Untreated Condition • Newly discovered drug • Patients in clinical trials: young males, early stages of disease; no other conditions • Sites of trials: USA, Europe (12 countries) • Clinical trial for submission: 12 months • Number of patients in trials = 200 started; 120 completed • Relieves symptoms of pain; improves creatinine clearance • Short-term reductions in blood pressure and arrhythmia HTA Drug Development

5. S1: New Drug for Previously Untreated Condition • On-going clinical trials: 3 years of date • Current clinical trials: women, advanced disease, older men • Similar findings • Manages symptoms, improves kidney and heart functions • Few patients: disease continues to progress • Few patients: no response • Few patients: severe adverse effects, including death HTA Drug Development

6. S2: New Drug Discovery: Better than Current • Background of Disease • Common condition affecting nearly 10% of population or 3 million Canadians • Chronic, progressive disease • Affects all ages but usually older adults HTA Drug Development

7. S2: New Drug Discovery: Better than Current • Current therapy • Very effective drug treatment available; safe when used as directed; injection • No significant improvements in therapy for nearly 30 years • Use requires monitoring for effectiveness • Very few side effects • Effective for most those affected • New needles and pumps reduce previous barriers (pain, difficulty injecting, collapsed veins) HTA Drug Development

8. S2: New Drug Discovery: Better than Current • Newly discovered therapy • + Oral therapy (previous attempts not successful) • + Gel capsules (no storage problems) • + Fast-acting (30 minutes to 1 hour) • - Active only 3 to 4 hours • - Difficult to get right dosage • - Requires constant testing and monitoring to adjust dose • - Highly variable absorption (peaks and valleys) HTA Drug Development

9. S2: New Drug Discovery: Better than Current • As head of the lab, what factors would you consider before investing in the development of this drug? • As a patient, what factors would you consider in deciding whether to participate in a new drug experiment or just to take the current drug? HTA Drug Development

10. S2: New Drug Discovery: Better than Current • Development challenges • Test against placebo not acceptable • Naïve (previously untreated) patients difficult to find • Test against current treatment not intended to demonstrate greater efficacy but non-inferiority (more difficult to prove • Quality of life difficult to measure with standard QoL tools • Need to prove long-term safety and effectiveness (against current therapy) • Cost of development substantial (but may not be able to charge more than current) HTA Drug Development

11. S2: New Drug Discovery: Better than Current • Clinical Trials (2 years) • Dosing based on levels of active ingredient comparable to current therapy (not independent dosing study) • One trial with three subgroups: mild, moderate and severe patients • Over 2,000 patients in 20 sites • Initial dosing inadequate for mild patients; benefits with increased dosing • Equivalent benefits for moderate patients • Superior benefits for severe patients (but study not designed to find superiority) • No different based on age, gender, ethnicity • Potentially serious allergy and side effects (gastrointestinal) HTA Drug Development

12. Bringing Together Questions and Key Learnings • In drug development, how does evidence of safety differ from evidence of efficacy? What are the implications? • Should standards of evidence be different for drugs for serious and/or previously untreated conditions versus drugs for conditions that are less serious and/or where other effective therapies are already available? • When is evidence “sufficient?” HTA Drug Development