Pharmaceutical Research Flashcards
Understand the fundamentals of pharma research, patient-centred research, research methods, RWE, and Natural History Studies
4 types of clinical outcomes assessments (COAs)
- Patient-reported outcomes (PROs): The patient reports how they feel or what symptoms they experience
- Clinician-reported outcomes (ClinROs): A clinician observes the patient and provides a clinical interpretation
- Observer-reported outcomes (ObsROs): A non-clinical observer, such as a parent, reports on the patient
- Performance outcomes (PerfOs): A patient’s performance is observed while completing a task
2 purposes of clinical outcome assessments (COAs)
- COAs provide data to support regulatory approval of new treatments
- COAs help improve patient care by providing insights into how patients respond to treatments
What is a COA and what are they used for?
A clinical outcome assessment (COA) is a tool used to measure how a patient feels, functions, or survives. COAs are used in clinical trials to evaluate the safety and effectiveness of new treatments.
Clinical endpoint
A clinical endpoint is a direct measure of how a patient feels, functions, or survives. It reflects the actual clinical benefit of a treatment.
- Survival, symptom improvement, disease progression
What are the clinical trial phases
- Phase I: Safety and dosage (small group).
- Phase II: Efficacy and side effects (larger group).
- Phase III: Large-scale testing for efficacy and safety.
- Phase IV: Post-market surveillance.
What is longitudinal prescription data?
Tracks and measures new, switch and repeat prescriptions, to give the prescription dynamics in a given therapy market
Surrogate endpoint
A surrogate endpoint is a substitute measure that is not itself a direct measure of clinical benefit but is expected to predict it. These are typically biological, laboratory, or imaging markers.
- Blood pressure reduction as a surrogate for reduced risk of heart attack
- Tumour shrinkage as a surrogate for overall survival in cancer trial
External comparator (EC)
A patient cohort derived from data external to a research study or “index trial”.
Single arm clinical trial
All participants receive the investigational therapy, and outcomes are compared to historical data or natural history studies of the disease.
Natural History Study
Observational studies that collect information about the natural history of a disease in the absence of an intervention, from the disease’s onset until disease resolution or the individual’s death. - FDA
When are natural history studies used?
- Natural history studies are used by researchers to understand disease progression in poorly characterised diseases. They are now being re-purposed to facilitate clinical development for rare diseases.
- Can be used to support rare disease trials when it is unfeasible or unethical to do a RTC
- Can accelerate drug development and increase the odds of regulatory approval
What are some ways to close evidence gaps?
- Leveraging RWE
- Conducting systematic literature review and meta analyses
- Collaboration with academic and clinical experts (engaging with KOLs and designing clinical trials to fill evidence gaps)
- Secondary data analysis and data integration (cross-industry data integration, longitudinal data)
- Modelling and simulation (health economics and outcomes research, forecasting)
- Patient-centred research (patient reported outcomes adn preference studies)
- Strategic partnerships and alliances (collaborating with regulatory bodies, industry partnerships)
- Custom surveys and market research (targeted surveys, market access studies)
How do natural history studies help with fixing limited knowledge about underlying disease mechanisms and clinical progression
Can help identify:
1. Genotype/phenotype relationships
2. Identifying sub-populations for a trial
3. Identifying patient reported outcomes
How do natural history studies help with undefined clinical endpoints?
They can be used to develop or validate biomarkers and establish the most relevant trial endpoints including surrogate endpoints
How do natural history studies help with patient and site engagement?
- Hard to find patients and research sites. Need to mine insights from academic landscape, centres of excellence and patient advocacy groups.
- Natural history studies can identify patients for future interventional trials, expediting future patient recruitment
How do natural history studies help with post-marketing commitments?
- Natural history studies play a critical role in fulfilling post-marketing commitments by providing comprehensive data on the progression and impact of diseases in the absence of treatment or under standard care
- Small sample sizes and accelerated approval pathways require post-marketing studies and benefit-risk management
Do natural history studies replace RCTs?
Do not replace RCTs but can provide an alternative that provides regulatory-grade evidence
Why are RCTs not ideal for rare diseasess?
- In rare diseases, there are often no existing treatments. Assigning patients to a placebo group denies them the opportunity to access a potentially life-saving or life-improving investigational therapy.
- Rare diseases inherently affect a limited number of people. Recruiting enough patients to form both an investigational and a control group can be extremely difficult, making traditional RCT designs impractical.
- With a small pool of eligible patients, splitting participants into two groups (treatment and placebo) reduces the statistical power of the trial, making it harder to detect meaningful differences in outcomes.
- ECs can recruit and publish results faster than an RCT as they require fewer patients and remove the barrier of randomisation to clinical trial participation
How do you figure out what data needs to be collected to define the comparator cohort in an NHS?
- Work with clinicians and KOLs to anticipate critical data variables (eligibility criteria, potential end points, confounding variables)
- Need to make sure you are collecting these variables during the natural history study
How do you figure out where NHS study data will come from?
- Asking too many questions, or requiring too much time from patients can negatively impact data quality and study retention.
- Can use either retrospective (using secondary data) or prospective data (collects data on patient group after study has begun).
- A prospectively designed natural history study isa research study that collects data on a patient group after the study has begun.
Who needs to be involved in the planning of an RCT?
Specialty clinicians, epidemiologists, biostatisticians, patient representatives, patient advocates
