Assorted Flashcards
What is a clinical trial?
A research project that compares 2 or more treatments in patients with a particular condition, to help generate high quality evidence about which is more effective
Who manages/coordinates a clinical trial?
Clinical trial unit of hospital
What is the hierarchy of evidence?
- Systematic reviews and meta-analyses
- RCTs with definitive results
- RCTs with non-definitive results
- Cohort studies
- Case-controlled studies
- Cross-sectional surveys
- Case series
- Case reports
What are the three phases of clinical trials and their main consideration?
Phase 1 - is the new treatment safe?
Phase 2 - is the new treatment effective?
Phase 3 - is the new treatment better than current SoC?
What are the features of phase 1 trials/
Small, typically less than 30 patients
Designed to find safe dose of new treatment and learn about side effects
What are the features of a phase 2 trial?
Typically up to 100 patients
May be randomised
Designed to find more information on side effects and how the treatment works for certain types of cancer
What are the features of a phase 3 trial?
Typically 100s of patients
Randomised
Designed to compare new treatment with standard and check which is better
Why is randomisation done?
Avoids bias: stops doctors assigning arms depending on how they fit the patient for example
Usually done by computer
What is blind and double blind randomisation?
Blind, patient doesn’t know what they are getting
Double blind, clinician doesn’t know either
Usually can’t blind RT trials
What kind of things would you need to consider if setting up a clinical trial?
Trial design. Do systematic review, has anyone else done this?
Practicalities: costing, staff planning
Collaborator negotiations: discuss with collaborators and funders
Set up permissions, ethics, MHRA
What might you need to do to participate in trial?
Facility questionnaire
Trial set up and permissions
Accreditation - trial QA
Site initiation visit
Delegation log
Recruitment
Data collection
What is trial accreditation and what does it involve?
Makes sure that patients entering the trial have same standards and quality of treatment
Questionnaire
Process document (how you will treat)
Benchmarking exercises (do some plans/contouring, they check it)
Site visit
Ongoing data collection
What can go wrong in a clinical trial?
Series adverse effects (these are reviewed, study may be terminated early)
Failing to recruit patients in an acceptable time frame
Failure to follow protocol
What is an example of trial protocol not being followed?
POG 8346 trial
Ewing sarcoma study, irradiate whole bone or just involved bone
Found no difference in LC between the two groups
Did find quality of RT made a difference,
No deviations from protocol, LC 5yrs 80%
Major deviation, 16%
What does being in a clinical trial involve for the patient?
Informed consent
Additional tests (potentially)
Additional data collection
Extra visits
Extra follow up
What are some advantages that patients could perceive of being in a CT?
Trial will advance cancer research and benefit future patients
May have access to treatment not widely available
May benefit if treatment is more effective
May think more appointments is reassuring and provide more support
What are some disadvantages that a patient might perceive of being in a CT?
New treatment could be worse
Could have severe side effects which haven’t been realised
Probably need more appointments
Might have extra costs associated with appointments, childcare/accomodation
Randomisation means no choice in treatment
What is PPI?
Patient and public involvement
Have patients/public involved in design and running of research, not being a research subject
PP should be involvd in all aspects of project
What are some practice defining trials?
CHHiP trial
PACE trial
START trial
FAST trial
What is the case for hypofractionation in prostate cancer?
Evidence that PC has low alpha beta ratio (~1.5 Gy), lower than surrounding tissues
Hypofractionating should produce good tumour control with late effects that are as good or better than standard
What did the CHHiP trial find?
60/20 is non inferior to 74/37 and could be new SoC
No significant difference in acute/late urinary toxicity
increase in grade 2+ bowel toxicity but this disappeared after 18 weeks
What did the PACE trial investigate?
36.25/5 vs surgery and vs 62 in 20
Suggests that patients don’t have worse toxicity, SBRT performs as well as standard RT
What did START trial investigate?
Moderate hypofractionation
START A and B
A: 13f in 5 weeks (41.6Gy and 39Gy) vs 50 in 25 over 5 weeks
START B: 50 in 25 over 5 weeks vs 40 in 15 over 3 weeks
At least as favourable as conventional fractionation
What did FAST and FAST FORWARD trials look at?
compared 50/25 over 5 weeks with 28.5/5 and 30/5 over five weeks
No significant difference in late effects
FAST FORWARD then looked at 5f in one week (26 or 27 in 5) vs 40 in 15
Non-inferior to 40 in 15
What factors resulted in an increase in radiation induced incidents and lead to RAGE?
Limited radiobiological understanding
Poor technique
Lack of consistent standards
Move to MV linacs
What is RAPPER?
Trial aiming to identify genetic varients associated with increased risk of side effects
