Ethics & Clinical Trials

1. What is a type A related to pharmacological action ADR? 2. What is type B ADR? unrelated to pharmacological action 3. What is a type C continuous reactions resulting from long-term drug use ADR? (e.g. analgesic nephropathy) 4. What is a type D - delayed reactions not observed until months/years folADR? lowing drug use - e.g.alkylating agents leading to carcinogenicity 5. What is a type E end of use reactions leading to a various types of withADR? drawal symptoms 6. What is efficacy? has the desired pharmacological activity 7. What regulatory bodies concern drugs being safe and efficient? - EMA - FDA - MHRA - WHO 8. What is used in preclinical testing? cell/animal studies 9. What is the pur- to see if the new treatment will be safe + will work on pose of preclini- people cal testing? 10. What is done to a number of lead compounds have been identified + initial show compunds screening tests have been conducted to present the pohave potential for tential of the compounds preclinical testing? 11. What procedures - basiic laboratory investigations does preclinical - in vitro testing testing include? - evaluation in an animal model ( in vivo ) 1 / 13 12. Pre-clinical test- - physiochemical evaulation ing - basic labo- - formulation studies ratory investigations? 13. Pre-clinical test- ames mutagenicity test ing - in vitro testing? 14. Pre clinical test- - initially using single species, sex etc. ing - evaluation in - progressing to a more complex tests using multiple an animal mod- species, comparators, higher order species el? 15. What is a key out- the determination of a safe initial dose for first in-man put from clinical clinical trials testing? 16. What is the pur- to assess the safety + effectiveness in humans pose of clinical trials? 17. What do Phase I clinical trials study? the safety of medication + treatment on people 18. What is used for a small number of healthy volunteers Phase I clinical trials? 19. What does Phase - collects safety + PK data by sampling body fluids I consist of? - assess patient behaviour = feelings/ mood/sleep/habitat - usually single dose/possibly rising dose studies 20. What is the aim exploratory, safety, tolerability + PK to support patient for Phase 1a clin- studies ic trials? 21. single dose 2 / 13 How many doses are given in Phase 1a clinical trials? 22. Describe Phase 1 - placebo controlled clinical trials; - randomised - double blind 23. How many sub- - healthy subjects jects are used in 40-60 Phase 1a clinical trials? 24. How long do 6 months Phase 1a clinical trials take? 25. What is the - adverse events data collected for - PK parameters Phase 1a /1b clin- - PD measures ical trials? 26. How many dos- doube/repeated dose es are used in Phase 1b clinicial trials? 27. How many sub- 30-50 subjects jects are used in Phase 1b clinicial trials? 28. How long do 6 months Phase 1b clinical trials take? 29. What is the dif- - dosage pattern ference between - number of subject involved 3 / 13 phase 1a/1b clinicial trial? 30. What is the pur- evaluates the safety + effectiveness of the drug + identifies pose of Phase II any potential side effects clinical trials? 31. Who are used for patients Phase 11a clinical trials? 32. What is given to intended clinical dose + regimen based on Phase 1a and patients in Phase 1b results 11a clinical trials? 33. Describe Phase - exploratory + preliminary safety + efficacy to support 11a clinical trials: decisions on whether to carry on or not - placebo controlled, randomised, + double-blind - sometimes open-label 34. How many sub- 50-200 subjects jects are used Phase IIa clinical trials? 35. How long are Phase 11a clinical trials? 9 months - 2 years 36. What is the - adverse events data collected for - PK parameters Phase IIa? - preliminary evidence of efficacy - proof of concept 37. What is the aim - confirmatory for Phase IIb clin- - dose selection to support registration ical trials? 4 / 13 38. Describe Phase - patients with 1/ more indication used IIb clinical trials: - selected dose levels + regimens compared to placebo + standard treatment - randomised 39. How many sub- 200-500 subjects jects are used in Phase IIb clinical trials? 40. How long are 2-3 years Phase IIb clinical trials? 41. What is the - dose response relationships data collected for - confirmation of clinical dose Phase IIb clinical - regimens for optimum efficacy, safety + tolerability trials? 42. What do Phase III clinical trials study? - study the safety, effectiveness + dosing on people - evaluate the effectiveness of the drug compared to standard treatments 43. What is the aim - confirmatory for Phase III clin- - efficacy ical trials? - safety data to support registration - may include pharmacoeconomic evaluation 44. Describe Phase - large scale studies in patients III clinicial trials: - patients with target indications but including different groups such as gender groups - selected dose levels + regimens compared to placebo + standard treatment - randomised + double-blind 45. What happens to reported in peer reviewed scientific journals + professional the results of meetings 5 / 13 Phase III clinical trials? 46. How many sub- 500-1000+ subjects jects are used in Phase III clinical trials? 47. How long do 2-5+ years Phase III clinical trials take? 48. What is the - demonstrating safety data collected for - efficacy in comparison with placebo/existing therapies Phase III clinical - pharmacoeconomic analysis trials? 49. What do Phase IV obligatory + post-marketing surveillance of patients to reclinical trials in- veal ADRs clude? 50. Who are the sub- treated patients jects in Phase IV clinical trials? 51. How many sub- 10,000+ subjects jects are used in Phase IV clinical trials? 52. How long are 2-4+ years Phase IV clinical trials? 53. When are Phase once the drug has been approved for use IV clinical trials conducted? 54. What medicines new medicines + vaccines that are under additional monhave an invert- itoring 6 / 13 ed black triangle symbol displayed in their package leaflet? (PIL + SmPc) 55. Who is respon- EMA sible for maintaining the list of black triangle products? 56. What is the yellow card scheme? mechanism of reporting adverse drug reactions of medicines in clinical use 57. What are the clin- - validity ical trials consid- - power & sample size eration? - bias 58. How do we know that outcome of a clinical trial is valid? it all comes down to trial design: - endpoints - participants - trial duration 59. What is power? - the proability of detecting a difference between study group (e.g. placebo + treatment group) when a true difference exists - typically trials use a power of 80% 60. What is sample size? calculated in order to give you the required power 61. What are the con- - placebo group trol groups? - comparator treatments - crossover trials 62. What are comparative trials for? - yield a treatment group (taking a new drug) + a control group (standard treatment/placebo) 7 / 13 - to evaluate if new drug is superior to existing treatment 63. What are parallel - simple + commonly used clinical design groups? - compares 2 treatments - test therapy is compared with a standard therapy 64. What are - involve the administration of 2 or more treatments to the crossover trials? same patient group over a specific period of time - each patient receives both treatments 65. What are randomised trials? - each group contain mix of participants / a process to 'balance' each study group - remove bias when allocating partiipants to treatment - knowledge of patient health may affect which group they are placed into 66. What does randomised trials help to gurantee? stastical validity of the study results 67. What is a type 1 - where the trials reports a difference between treatment error? A and b, where none actually exists (false positive) - probability of incurring error = significance of result ( p value < 0.05) 68. What is type 2 er- where no difference is found between treatment groups ror? where one actually does exist (false negative) - probability of avoiding error = power of trials (80=90%) - more dangerous than type I, can miss an effect that exists 69. Why is sample size is critical? if too small, observed difference between trial groups may bey due to chance 70. What are the risk unknown effects for participants? 8 / 13 71. What are the ben- might be more efficacious than current treatment efits for participants? 72. Why not give not ethical to remove treatment group cancer patient a placebo? 73. What is considered when designing a clinical trial? - desired outcomes - adequate representation of the intended patient pop - stastical validity - ethical of placing patient with an illness on the placebo group of a trial 74. What is ethics? - concerned with what is good for individuals + society + is also described as moral philosophy (affects how people make decisions + lead their lives) 75. Why were ethical to help protect those involved in research guidelines established? 76. What is informed an ethical principle that research participants be told consent? enough to enable them to choose whether they wish to participate (patient fully aware of risk/benefit, can withdrawn any time) 77. What are the 7 major principles that guide the conduct of ethical research? 1) social + clinical values 2) scientific validity 3) fair subject selection 4) favourable risk-benefit ratio 5) independent review 6) informed consent 7) respect for potential + enrolled participants 78. What is animal research? - looking at how the body works (cause of disease/disease progression) - assessement of treatment (safety + efficacy) 9 / 13 79. Explain the regulation on animal research (licenses)? - certificate of designation = research can only happen in institutes which have approp animal accomodation + vet facilities (also show natural behaviour as possible, trying to be ethical, natural habitat as possible, if restrict them can change physiological function) - project license = research can only be part of an approved research/testing programme which has been granted this license - personal license = research can only be carried out by people with sufficient training/skills/experience 80. What are the 3R's? replace reduce refine 81. What is replace? - replace the use of animals with alternative techniques/avoid use of animals together - e.g. questionnaire - studying in human volunteers/observation studies - measure risk of illness/death in exposed identical pop + compare unexposed = epidemological studies 82. What are the alternatives to animal? (replace them) - computer based = in silico models - in vitro (cells) - tissues (ex vivo) - reduce chance of using whole animal 83. What is reduce? - reduce number of animal used - obtain info from fewer animals/ more info of same animal - picking an animal closest to human - reduce by using correct species of animal 84. What is refine? - the way experiments are carried out, to make sure animals suffer as little as possible 10 / 13 - incl better housing + improvement to procedures which minimise pain + suffering 85. What are the limi- - money, time tations to refine? - limited amount of data available - lack of guideline of how put refinement in place - lack of motivation/training 86. Bias in clinical randomisation of participant groups trials could be minimised by..... 87. What is the inclu- 18-60 sion criteria age? -if under too young = no formed consent 88. What is the 14 units per week of alcohol units NHS recommendation of alcohol intake? 89. Can type I diaNo - extra complication betes be in clinical trials? 90. What does it - not havng condition controlled therefore include in a mean by unclinical trial controlled 500mg MET? (metformine) 91. Would you inNo clude a patient who has partial seizures in a clinical trial? 92. If someone is yes to lab result would you - something abnormal detected - not include 11 / 13 include them in clinical trial? 93. If seizures not as- - not include trial as could be epilepsy - be a concern sociated with alcohol what does it mean? 94. What is the max 2000mg MET? 95. What is controlled MET daily? if in clinical trial can interfere as condition already treated 96. If patient has his- - not enough info whether be placed clinical trial or not tory of depression? 97. You are working on panel at uni assessing the use of animal testing. Why animal testing should be banned at uni? (5 marks) - expensive - no informed consent = unethical - might induce harm to an animal = pain + suffering despite refine an animal - animals are not humans so for that specific condition would still see differences which may lead to misleading info - some species more expensive than others, 3 licenses + training.... (expensive) - might genetically modify an animal = biohazard - animal rights - greater diversity of animal than human could influence the result - redoing animal study time time-consuming + expensive -advancements in technology have provided alternative methods, such as in vitro testing that can reduce the need of animal testing 98. You are work- human life considerable more valuable than human ing on panel - animal shorter lifespan = generate more data - can at uni assessing compare epidemiological studies 12 / 13 the use of animal testing. Why animal testing is valuable + needs be continued? - not all animal studies are related to treating humans, some related to animal - allow researchers to study the effects of new treatment in animals before they are tested on humans - help ensure safety + efficiency of drugs before they reach clinical trials - can provide valuable insight into disease mechanisms 13 / 13