ࡱ> svut!8(m  < !|(www.nres.npsa.nhs.uk8http://www.nres.npsa.nhs.uk/|(www.nres.npsa.nhs.uk8http://www.nres.npsa.nhs.uk/|(www.nres.npsa.nhs.uk8http://www.nres.npsa.nhs.uk/8www.myresearchproject.org.ukHhttp://www.myresearchproject.org.uk/`/ 0DArialngsʤ,v0,0$DWingdingsʤ,v0,0$@ .  @n?" dd@  @@`` (d,,>>,,()  ()  ** HHDEFGHILMNOPQRSUVWXYZ[`bac 0AA@8:;wʚ;ʚ;g4KdKdD0ppp@ <4ddddph0ʤ <4BdBdp̨080___PPT10 pp?  %.)The role of the Research Ethics Committee1Chris Foy Gloucestershire RDSU and South West RECA trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system  Improvements in 2004=Clinical Trials Regulations (implementing EU Directive) in force in UK; one application per trial, and 60 day time limit on REC deliberations COREC decides same working practices will apply to all applications One application form for all UK; online applications only One set of operating procedures (SOPs) for all UK>>!Current DevelopmentsSeptember 2006  Human Tissue Act 2004 applies to research use of any samples that include cells October 2007  Mental Capacity Act 2005 applies to research on adults who lack or lose capacity February 2008  Integrated Research Application System (IRAS) brings together ethics, R&D and other forms. See www.myresearchproject.org.uk OZO01MWhat is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Preparing to apply>Design your study Write your protocol BEFORE tackling the ethics form Get scientific peer review (the sponsor s job) Get key people s agreement, including funding (in principle) if needed Visit www.nres.npsa.nhs.uk to start on the application form; online system with ID and password   0  Getting the application ready$The form is tailored to your type of study (e.g. no drugs questions if not a drug trial) www.nres.npsa.nhs.uk has model information sheets and consent forms for participants; you don t have to copy them slavishly! Student projects (below doctorate) should be in the name of the supervisor Note that the sponsor has to sign the application (or a letter making the same declaration) before you can submitZY&0Ym Submitting your applicationA checklist on www.nres.npsa.nhs.uk lists the documents you need If it s a medicinal trial, a medical device study, a study in prisons, or any study in two or more Strategic Health Authority areas, phone the Central Allocation System Otherwise, phone your local REC co-ordinator (If you phone the wrong place you will be redirected)MM0# Submitting your applicationYou  lock your form, which is then finalised Send one signed paper copy of the application, and the checklist, and all the other documents (CV, protocol, information sheet and consent form, and questionnaires etc. as necessary) to the REC Student application needs supervisor s signature and CV in addition The REC does the photocopying SS What happens nextThe REC will invite you to attend the meeting, with an appointment time It s not compulsory to attend, but it s helpful The REC understands that people may be nervous about attending As at outpatients, REC meetings can get behind time on the day Who will be there?Maximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists The Co-ordinator will be there, and there may sometimes be observersQuestions from the CommitteeYou don t need to  present your study  Committee members will have read it They will most likely have some questions The Chair of the meeting will control the flow of questions, so they shouldn t come from all sides at once.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion   ` 3L:̪3fܗ` =XL=xt=x̙` 3fL3[[E)̙` ff` 3F433` f3ϫ̙` ff̙f` @K=3NLGwt` geff>?" dd@,?" dd@   " @ `"  n?" dd@   @@``PT    @ ` `6p>> &@(  Z  # "2   BCDEF"d@ @`s"*     c BCDEF"v @ @`" *   BtCDEF"d@ tttt@`s"*  i` Z P # "P  c B CDEF @))<  _ wv J c /JVJBeW<_JW R"R"F(.6 JJJQ^tkK-,&k < < TX@`"x\  P  " P   BCDE<FF|urBAwK-Id<|u $@`"lP   BCaDE@FJ$6B*r0a6T~~xZB<$$"$@`"u / [   BzCDE,F6  (<y6"zL^Z6@`" 5P D   BCBDE4F> rN<`*B~rr @`",d   B*CHDE4F> $  $**0 H$$ @`"  d  c TBCDEF @88 1$s[6C6&fH~fM~ vpjd^ L@. $*<HW090HH<< HC<=<1HNZxNrt@`"Z  # "^  BmCDEdFn<BlU1mg~Or+ZH6$k_H B 6*48@`"F  BCDEXFb`$ <hZg gnm\=.0@`"F  BGC<DEXFb 5;A*G6G<;6/*$* 000$.0@`"&m,&  BCDEHFR0Hr `6`<fHlTx`r`f6&(@`"W  B;C<DE4F> ;))$/*565</6#0$;; @`"Kf  (BCDEhFr$*TM/TYB;$  /MSYe } $$68@`"  6t? 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 ()  ** HHDEFGHIRUVWXYZ[`badefghiklmnopqrst 0AA@8:;wʚ;ʚ;g4BdBd$0ppp@ <4ddddPh0ʤ <4BdBdP̨0T80___PPT10 pp?  %SA trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 days .( /) 0* 1+   !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~8Root EntrydO)pTCurrent User,SummaryInformation(VUPowerPoint Document(zDocumentSummaryInformation8 .  @n?" dd@  @@`` p,,>>,,()  ()  ** HHDEFGHIRUVWXYZ[`badefghijklmno 0AA@8:;wʚ;ʚ;g4BdBd$0ppp@ <4ddddPh0ʤ <4BdBdP̨0T80___PPT10 pp?  %A trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 days "8John Snow s quasi-experiment (" )#3A modern proposal to experiment without randomising44( *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies '!Finally $ :  H$(  Hr H S < ``   r H S  `  H H 0޽h ? 3F43380___PPT10.D$ : PT$(  Tr T S   ``   r T S   `   H T 0޽h ? 3F43380___PPT10.m{ : >6@(  x  c $  ``   x  c $|  `     6 dZ 0 The Great Experiment 1850s London supplied by two water companies One intake in Central London Other intake at Thames Ditton Compared cholera mortality by source Water-borne hypothesis confirmed Organism not discovered for 30 years 1 2 xlH  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $p  ``   x  c $p  `   H  0޽h ? 3F43380___PPT10.%L :  (  x  c $d#  ``   x  c $d(  `   i  6$ڈ  B Change standard treatment protocol every six months Compare one cohort with the next Avoids explaining about randomisation But imports other problems: is the protocol change an undeclared experiment? 1 2 H  0޽h ? 3F43380___PPT10.%L : (  x  c $X3  ``   x  c $X8  `   M  6 7I{  To gain a broad picture of health, lifestyle, satisfaction with services etc. Usually postal Looking for response rate 60%+ Layout and content are important Need reminders 1 2 H  0޽h ? 3F43380___PPT10.%L :  (  x  c $C  ``   x  c $H  `   c  64 ,  Burden on respondents One, two or more reminders? Should replies be confidential (numbered, for reminders and data linkage)? Or should they be anonymous (especially where subject is sensitive)? 1 2 H  0޽h ? 3F43380___PPT10.%L : (  x  c $S  ``   x  c $X  `     6܋   DTime taken  payments may be offered Possibility for upset For home interview, safety of researcher Stigma   I saw the bedwetting interview man on your doorstep  1 2 H  0޽h ? 3F43380___PPT10.%L : (  x  c $c  ``   x  c $h  `   r  6| T} Recruit a group and follow them through time Looking for association between factors at baseline and disease later Follow-up period may be years or even decades Needs lots of contact to keep cohort together"10 Z2 H  0޽h ? 3F43380___PPT10.%L` : P`(  x  c $,ϰ ``   x  c $Ӱ `  (  6@ z  Looking for association between disease and factor Used where disease is rare: survey wouldn t find enough cases Choose one or more controls per case Typically controls are matched on age and sex 1 2 H  0޽h ? 3F43380___PPT10.%L : $`(  x  c $y? ``  ? x  c ${? ` ? |  6$/  Compare factors between cases and matched controls to estimate relative risk Can be difficult to explain to controls why they are in study Example: survey of parents of children who had meningitis, and control parents 1 2 H  0޽h ? 3F43380___PPT10.%L : VNp(  x  c $  ``   x  c $h۰ `     6  H A sample size calculation should be done, with reasonable estimates of the benefit sought Too small a study  unethical because it exposes participants to burden and hazard for no scientific benefit Too large a study  unethical because wasteful of participants"10 Z2 H  0޽h ? 3F43380___PPT10.%L : (  x  c $, ``   x  c $, `  n  6 zv Used to gather a lot of information from relatively few respondents Don t use random sampling Therefore no claim to be representative Doesn t limit respondents to investigator s agenda Not the  soft option - analysis is hard work 1 2 H  0޽h ? 3F43380___PPT10.%L : 4,(  x  c $( ``   x  c $- `    6|z  &Research involves a degree of risk Jenner wouldn t have discovered smallpox vaccination without risk RECs ensure that risks are reasonable and subjects are aware of them - not that risks are nil Plenty still to discover 1 2 ,#<sH  0޽h ? 3F43380___PPT10.%LrL@"l+O=Bz#Sy-< 2'(m / 0DArialNew ʤ v0 0"DWingdingsʤ  ՜.+,0  $ , On-screen Show$Gloucestershire Hospitals NHS Trustz$ (Arial WingdingsTimes New Roman Mountain TopEthics of statistical researchResearch on human subjects Ethical principles for researchA trial that went wrong A study that couldnt go wrong?Both need ethical review!Research Ethics Committees in UKWhat is the REC for?&How does the REC do this in practice?What is the REC looking for?What is the REC looking for?What is the REC looking for?)Special care for vulnerable participantsWho are the members?The Committees optionsRandomised controlled trialsRandomised controlled trialWhy a control group?Why randomise?Ethics of random allocation%Sample wording for information sheet BlindingEthics of blinding4A modern proposal to experiment without randomisingQuasi-experimentJohn Snows quasi-experimentSurveysPostal survey problems_zfoycfoycInterview survey problems Cohort studyCase-control studyCase-control study$Sample size in quantitative studiesQualitative studiesPublication ethicsFinally2,Quasi-experiment "8John Snow s quasi-experiment )#3A modern proposal to experiment without randomising44( *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies '!Finally 0 : 0(  x  c $dC  ``   x  c $dH  `   H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $XS  ``   x  c $XX  `   H  0޽h ? 3F43380___PPT10.%L0 :  0(  x  c $c  ``   x  c $h  `   H  0޽h ? 3F43380___PPT10.%L0 : 00(  x  c $s  ``   x  c $x  `   H  0޽h ? 3F43380___PPT10.%L, : @,(  x  c $  ``   x  c $  `     6 d  RSubjects fall into two or more groups Not allocated by investigator Take advantage of changing conditions Also called  natural experiment or  experiment of opportunity  1 2 H  0޽h ? 3F43380___PPT10.%Lr /.Pi,.03I5+ }92 '(m / 0DArialNew ʤ v0 0"DWingdingsʤ v0 0 DTimes New Roman v0 0@ .  @n?" dd@  @@`` v ,,>>,,()  ()  ** HHDEFGHIRUVWXYZ[`badefghiklmnoprstu 0AA@8:;wʚ;ʚ;g4BdBd$0ppp@ <4ddddPh0ʤ <4BdBdP̨0T80___PPT10 pp?  %A trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 daysEthics of random allocation .($Sample wording for information sheet%%( 0*Blinding 1+Ethics of blinding 2,Quasi-experiment "8John Snow s quasi-experiment )#3A modern proposal to experiment without randomising44( *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study 3- $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies '!Finally Y : Y(  r  S ̝ ``   r  S  `  -  6,ˮdt  To a patient unused to the idea, having treatment chosen by tossing a coin sounds unnerving, even callous Careful explanation is called for 1 2 H  0޽h ? 3F43380___PPT10.%Li : i(  x  c $dC  ``   x  c $dH  `   1  6w Sometimes because we do not know which way of treating patients is best, we need to make comparisons. Patients will be put into groups and compared. The groups are selected by a computer which has no information about the individual, i.e. by chance. Patients in each group then have a different treatment and these are compared. In this study, you will have a 50:50 chance of receiving X or Y. 1 2H  0޽h ? 3F43380___PPT10.%L : H@ (  x  c $c  ``   x  c $h  `     6z- :In a drug trial, clinician or subject report may be biased by knowledge of allocation Can avoid this if subject does not know the allocation (single-blind) If clinician does not know either, this is called double-blind Requires identical-looking placebos 1 2 H  0޽h ? 3F43380___PPT10.%L : d\0(  x  c $s  ``   x  c $x  `     6T zG  VNeeds explanation Need a mechanism for prompt breaking of the blind in case of an adverse event  This is a double blind trial which means that neither you nor your doctor will know which group you are in (although if your doctor needs to find out they can do so). * 1 2` H  0޽h ? 3F43380___PPT10.%L0 : P0(  x  c $P ``   x  c $ `  H  0޽h ? 3F43380___PPT10.%Lr,9a.e0 riRm3Nr-9t3< l+(m / 0DArialNew ʤ v0 0"DWingdingsʤ v0 0 DTimes New Roman v0 0@ .  @n?" dd@  @@`` H@|$,,>>,,()  ()  ** HHDEFGHIRUVWXYZ[`badefghiklmnoprstwxyz{ 0AA@8:;wʚ;ʚ;g4BdBd$0ppp@ <4ddddPh0ʤ <4BdBdP̨0T80___PPT10 pp?  %U#A trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 days4/ 50 61 72Why a control group? 83Why randomise?Want      !"#$%&'()*+,-./012345679:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqr to compare the effect of the treatment and control Need to remove other influences These include patient and clinician preference So don t let patient or clinician choose Choose by predetermined rule -  random Ethics of random allocation .($Sample wording for information sheet%%( 0*Blinding 1+Ethics of blinding 2,Quasi-experiment "8John Snow s quasi-experiment )#3A modern proposal to experiment without randomising44( *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies '!Finally 0 : p0(  x  c $\ ``   x  c $4 `  H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $ޮ ``   x  c $} `  H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $d ``   x  c $d `  H  0޽h ? 3F43380___PPT10.%L :  (  x  c $\ ``   x  c $\ `  x  6  Optimistic about new treatment But need to be sure that benefits wouldn t have happened anyway What is additional benefit of new treatment against best existing treatment? So compare some subjects who get new with some who get existing 1 2 H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $  ``   x  c $t  `   H  0޽h ? 3F43380___PPT10.%L : ^V (  x  c $c  ``   x  c $h  `     6z- PIn a drug trial, clinician or subject report may be biased by knowledge of allocation Can avoid this if subject does not know the allocation (single-blind) If clinician does not know either, this is called double-blind Requires identical-looking placebos6V1 21 2 H  0޽h ? 3F43380___PPT10.%Lr(t04PR¤2t8 -(m / 0DArialNew ʤ v0 0"DWingdingsʤ v0 0 DTimes New Roman v0 0@ .  @n?" dd@  @@`` ph(,,>>,,()  ()  ** HHDEFGHIRUVWXYZ[`badefghiklmnoprstxy(z{|}~ 0AA@8:;wʚ;ʚ;g4BdBd$0ppp@ <4ddddPh0ʤ <4BdBdP̨0T80___PPT10 pp?  %N%94Ethics of statistical research :5 ;6 <7 =8 A trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 days50Randomised controlled trials 61Randomised controlled trial 72Why a control group? 83Why randomise?Want to compare the effect of the treatment and control Need to remove other influences These include patient and clinician preference So don t let patient or clinician choose Choose by predetermined rule -  random Ethics of random allocation .($Sample wording for information sheet%%( 0*Blinding 1+Ethics of blinding 2,Quasi-experiment "8John Snow s quasi-experiment )#3A modern proposal to experiment without randomising44( *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies '!Finally  : _W(  x  c $<  ``   x  c $<  `     6T   QChris Foy 8 July 2008 0( 2 H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $։  ``   x  c $4t  `   H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $  ``   x  c $h  `   H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $  ``   x  c $  `   H  0޽h ? 3F43380___PPT10.%L0 : 0(  x  c $Y  ``   x  c $  `   H  0޽h ? 3F43380___PPT10.%L : (  x  c $ޮ ``   x  c $} `  Z  6 M, First reported trial 1948 Tuberculosis: streptomycin and bed-rest vs. bed-rest only RCTs called  clinical trials when therapy is tested Don t have to be of therapy: e.g. housing improvements and health  1 2 TtH  0޽h ? 3F43380___PPT10.%L : \T&'(  x  c $d ``   x  c $d `     `?xaxa1 ?P ^  61?   Z vB;vB;1?e l  b population 0      XB  01?   ^B   61? ^B   61?  ^   61?n r    Z(SvB;vB;1?_< f _group 10     ^   61?{ r   ZvB;vB;1? <  _group 20     ^B  61?z W  Z䑮vB;vB;1?_*f _Outcome0       ZvB;vB;1?k Ur  _Outcome0     ^B  61? z W L q8 m  # 8    c BCDEF1?n @qk ?   c B-CXDEF1?<W,,< @> k   c BCDEF1?1c1 @s8 m N K Z   K Z f2  61?h  f2  61?kK j f2  61?2 ` f2  61?  f2  61?a  f2  61?. [ f2  61?$ v W f2  61?b  f2   61?' Z f2 ! 61? 7  " ZxBxaxa1?K R! G new treatment0  # ZȰxaxa1? ! Kcontrol treatment0 d $ <1?F d % <1? 1^B & 61?``^B ' 61?, H  0޽h ? 3F43380___PPT10.%Lr,45 :9P0h5.=< -(m / 0DArialNew ʤ v0 0"DWingdingsʤ v0 0 DTimes New Roman v0 0@ .  @  Fonts UsedDesign Template Slide Titles$n?" dd@  @@`` ph(,,>>,,()  ()  ** HHDEFGHIRUVWXYZ[`badefghiklmnoprstxy(z{|}~ 0AA@8:;wʚ;ʚ;g4BdBd$0ppp@ <4ddddPh0ʤ <4BdBdP̨0T80___PPT10 pp?  %p%94Ethics of statistical research :5Research on human subjects ;6 <7 =8 A trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 days50Randomised controlled trials 61Randomised controlled trial 72Why a control group? 83Why randomise?Want to compare the effect of the treatment and control Need to remove other influences These include patient and clinician preference So don t let patient or clinician choose Choose by predetermined rule -  random Ethics of random allocation .($Sample wording for information sheet%%( 0*Blinding 1+Ethics of blinding 2,Quasi-experiment "8John Snow s quasi-experiment )#3A modern proposal to experiment without randomising44( *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies '!Finally 0 : 0(  x  c $։  ``   x  c $4t  `   H  0޽h ? 3F43380___PPT10.%Lr:=48bu6= -(m / 0DArialNew l. v0 0"DWingdingsl. v0 0 DTimes New Roman v0 0@ .  @n?" dd@  @@`` x ',,>>,,()  ()  ** HHDEFGHIRUVWXYZ[`badefghiklmnoprstxy(z{|} 0AA@8:;wʚ;ʚ;g4KdKd$0ppp@ <4ddddPh0D. <4BdBdP̨080___PPT10 pp?  %N%94Ethics of statistical research :5Research on human subjects >9Ethical principles for research A trial that went wrongEight healthy volunteers recruited for first human use of a monoclonal antibody Two randomly assigned to placebo The other six suffered serious adverse reactions; some were life-threatening Investigation found poor practice MHRA now has special precautions for Phase I trials>A study that couldn t go wrong?A student wishes to interview four cardiac rehabilitation patients about their experiences Relatively harmless But what about the pressure to take part? And if poor care is revealed? And the safety of the student?Both need ethical reviewBut the depth of the review should be proportionate to the risks and inconvenience to participants The National Research Ethics Service (formerly COREC) is moving towards this Research Ethics Committees in UK!!( Started in 1960s By 1980s, there were over 200, each with their own application form and working practices Next to impossible for those conducting UK-wide research; people took short cuts 1991 to 2001  DH moves towards standardising and simplifying the system What is the REC for?\A REC  should safeguard the rights, safety and well-being of all trial subjects. Special attention should be paid to trials that may include vulnerable subjects. (ICH GCP)  %How does the REC do this in practice?&&("Committee has to judge the benefit that could arise from the research against the risks and inconvenience to participants There s no fixed rule for striking this balance, hence a committee weighs it up, not an individual For student studies, the benefit may be educational What is the REC looking for?DNo-one is obliged to participate in research  it s a favour, so & How are participants identified, approached and recruited? Is there a clear explanation of what will happen to them? Do they give genuinely informed consent? Do they know they can withdraw at any time without disapproval? #Z#What is the REC looking for?7What about the risks (side effects) and inconvenience (time and travel)? What about their study data? Who will see it? How long will it be kept? What about tissue samples (including body fluids)? How long will they be kept? Could they be used in other studies? Will DNA be extracted? Will GPs be informed?8Z8What is the REC looking for?PWhat will happen at the end of the study (will study drug continue to be available)? What about complaints? Does NHS indemnity apply? Is insurance needed? Has the scientific review job been done, to show that the research is capable of delivering benefit? Where will the study be published? Will participants get to know the results?QZQ(Special care for vulnerable participants))(RChildren (Gillick guidelines may apply) Adults without capacity to consent to study (mental illness, learning difficulty, or unconscious) Those with a terminal illness Prisoners Dependent on the investigator (e.g. nursing home residents, students) Those whose English isn t up to informed consent *Z*  Who are the members?PMaximum of 18 members One-third of these are  lay The rest are  expert  doctors, nurses, allied professionals, statisticians and pharmacists Open recruitment process.The Committee s optionsFavourable opinion Provisional opinion with a set of written questions No opinion, while the Committee consults a specialist referee (rare) Unfavourable opinion All to be done in 60 days50Randomised controlled trials 61Randomised controlled trial 72Why a control group? 83Why randomise?Want to compare the effect of the treatment and control Need to remove other influences These include patient and clinician preference So don t let patient or clinician choose Choose by predetermined rule -  random Ethics of random allocation .($Sample wording for information sheet%%( 0*Blinding 1+Ethics of blinding )#3A modern proposal to experiment without randomising44( 2,Quasi-experiment "8John Snow s quasi-experiment *$Surveys +%Postal survey problems ,&Interview survey problems -' Cohort study #Case-control study $Case-control study %#Sample size in quantitative studies$$( & Qualitative studies ?:Publication ethics '!Finally  : n(  x  c $Tc  ``  c  x  c $Uc  ` c  6  6Wc YC rChris Foy 8 July 2008 Gloucestershire R&D Support Unit South West Research Ethics Committee Chris.Foy@glos.nhs.uk s0( 2s ]H  0޽h ? 3F433___PPT10i.%L+D=' = @B + : .(  x  c $h+ ``   x  c $d `    6C=, 4Research funder balances costs of research against benefits But what about the inconvenience and risks to human subjects (participants)? There is a well-developed system for research in the health field (not only for trials of medicines) Other fields: education, criminal justice & 5 2   H  0޽h ? 3F433___PPT10i.%L+D=' = @B + : ?(  x  c $8= ``  = x  c $  ` =   6t , ENon-maleficence Beneficence Justice Autonomy Dignity Welfare Rights F5 2F  7H  0޽h ? 3F433___PPT10i.%L+D=' = @B + : e(  x  c $(2t  ``  t  x  c $2t  ` t  -  6D4t w Sometimes because we do not know which way of treating patients is best, we need to make comparisons. Patients will be put into groups and compared. The groups are selected by a computer which has no information about the individual, i.e. by chance. Patients in each group then have a different treatment and these are compared. In this study, you will have a 50:50 chance of receiving X or Y.0 2H  0޽h ? 3F433___PPT10i.%L+D=' = @B +^ : um (  x  c $,  ``   x  c $ॏ  `     6H=v& gEthical duty to publish, or the study might as well not have been done Publication needs as much care as lab or field procedure There has been little training for authors, editors, peer reviewers www.equator-network.org J1 20 21 2 H  0޽h ? 3F433___PPT10i.%L+D=' = @B +r(6.Tq9 Vd%h> mv6z?Root EntrydO)Xy@Current User,SummaryInformation(VUPowerPoint Document(z      !"#$%&'()*+,-./012345679:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrxz{|w  Foy ChrisDocumentSummaryInformation8՜.+,D՜.+,4  $ , On-screen Show$Gloucestershire Hospitals NHS Trustz$ (Arial WingdingsTimes New Roman Mountain TopEthics of statistical researchResearch on human subjects Ethical principles for researchA trial that went wrong A study that couldnt go wrong?Both need ethical review!Research Ethics Committees in UKWhat is the REC for?&How does the REC do this in practice?What is the REC looking for?What is the REC looking for?What is the REC looking for?)Special care for vulnerable participantsWho are the members?The Committees optionsRandomised controlled trialsRandomised controlled trialWhy a control group?Why randomise?Ethics of random allocation%Sample wording for information sheet BlindingEthics of blinding4A modern proposal to experiment without randomisingQuasi-experimentJohn Snows quasi-experimentSurveysPos_zfoycfoyctal survey problemsInterview survey problems Cohort studyCase-control studyCase-control study$Sample size in quantitative studiesQualitative studiesPublication ethicsFinally  Fonts UsedDesign Template Slide Titles$@ T_AdHocReviewCycleID_EmailSubject _AuthorEmail_AuthorEmailDisplayName ӬFEthics in statistical researchChris.Foy@glos.nhs.uk