Julie James, Aldona Kirkham & Anne Moore UHL Clinical Trial Monitors & Trainers January 2018

1. Julie James, Aldona Kirkham & Anne MooreUHL Clinical Trial Monitors & TrainersJanuary 2018

2. Informed Consent for Research

3. Session Objectives: What is Informed Consent? Why do we need Informed Consent? How do we obtain Informed Consent? What are the implications of not gaining Informed Consent?

4. Group 1: Write a short statement to explain what is Informed Consent Group 2: Give 4 reasons why we need Informed Consent

5. What is Informed Consent? “Process by which a subject voluntarily confirms his/her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subjects decision to participate. Informed Consent is documented by means of a written, signed and dated informed consent form” (ICH-GCP E6 1.28 1996)

6. Why do we need Informed Consent? • Without fully informed consent: • The subject can sue • Ethics/Trust approval may be withdrawn • Future proposals may not be supported • Inspection/Audit requirements may not be met.

7. Points to consider before commencing the consent process.. What should you consider prior to commencing the consent process? Group work - using the laminated slips, put the statements under the correct headings

8. Points to consider before commencing the consent process..

9. Points to consider before commencing the consent process..

10. Responsibilities…The Principal Investigator is ultimately responsible for Informed Consent Everyone is responsible for…. • Approvals: on the original ethics submission, R&D approval, consent training and that the responsibility has been delegated and reflected in the DOA • Appropriately trained: GCP training, consent training, must show evidence of training in site file • Familiarity with protocol and disease: Must be familiar with protocol and the disease under study and alternative treatments. • Communicate information: You must be able to communicate the information objectively. Your Subject must be made aware of potential risks and benefits • Time and resources: You must allow adequate time for discussion and have an awareness of participants circumstances

11. The Process of Informed Consent Identify suitable participants against the inclusion/exclusion criteria This process must take place before any trial related activity occurs

12. The Process of Informed Consent How much time ?

13. Question… In the ethical application the researcher stated the participant would have 3 days to consider participating in the study. However, Mr Smith contacts the researcher after one day and wishes to attend and consent to the study. Is this appropriate? If the application stated up to 3 days this would be appropriate. However if the application stated a minimum of 3 days to consider, consent should not be taken until this time has passed. If the original recruitment time frame requires changing to improve recruitment, a substantial amendment must be submitted

14. Getting the time right.. Researcher not allowing the correct amount of time for potential participants to consider taking part in a study is frequently an audit finding. The Original IRAS form will detail exactly how much time is required. This time must be adhered to. If this timing is causing a problem with recruitment, it is possible to change the amount of time allowed but this has to be done via a substantial amendment. CHECK YOUR ORIGINAL IRAS FORM

15. Delivery of Information

16. Delivery of Information

17. Delivery of Information Is this a good way to deliver information?

18. Correct Completion of a Consent Form Are YOU getting it right?

19. Correct Completion of a Consent Form • Record study & participant ID to facilitate identification • All boxes must be initialled- (ticks in boxes will not invalidate a consent form) • All mandatory statements must be completed • NO handwritten changes to approved consent forms, UNLESS correcting participant/researcher errors or when the participant is required to indicate their preference in relation to a statement • Participant & researcher names should be completed in block capitals • Where an error has been made on the consent form, only the person who has made the error can correct it

20. Question…. Whilst reviewing your investigator site file, you discover a number of consent forms have been incorrectly completed. What should you do?

21. Documentation What should you include when documenting the consent process in the medical notes?

22. Documentation It is essential that you provide evidence of the consent process in the participants medical records/appropriate records. You need to complete a written entry in the main body of the notes to detail the study name/number, when the information sheet and version was given to the participant. When full written consent was obtained, a description of what was discussed, that questions were answered where appropriate, the next visit date (if applicable), your name, role and contact details. This should then be signed and dated. Remember to also document subsequent visits and participants willingness to continue to in the study.

23. Question…. A participant has been approached with a view to taking part in a clinical trial. The eligibility criteria states that the participant must have a resting heart rate of between 40 to 50 bpm. The researcher checks the heart rate using a heart rate monitor and this shows that the participant is eligible to participate. The researcher then proceeds with the consent process, the consent form is signed and the process is documented in the medical notes. Is this acceptable?

24. Question…. A researcher has taken informed consent from a patient. On filing the original copy of the consent form in the site file realises that the patient has been consented on a superseded version. What should the researcher do?

25. Question…. Participants are being approached to take part in a study which involves completing a questionnaire. The consent form is being sent together with the questionnaire to the participant. The participant completes the consent form and the questionnaire and returns it to the researcher. Is this an acceptable method of obtaining informed consent?

26. Question…. A patient is invited to attend for a screening visit to take part in a complicated urology study. The patient is a non English speaker and brings her friend who works at the hospital to interpret. Is this acceptable?

27. Ongoing consent as a process Informed consent is an on-going process and consequently researchers must ensure that participants: continue to understand what the research is about and what their participation involves. are provided with any new information which might influence their decision to continue their participation in the research. Re-consent must be conducted in a timely manner. It is generally expected that participants are re-consented at the next visit defined in the protocol. Special consideration should be given when duration between visits are long. An unscheduled visit may be necessary where a safety issue comes to light. It is recommended that the Investigator tracks the consent status of each participant when a new version of the patient information leaflet/consent is implemented.

28. Ongoing consent as a process Revisiting informed consent is done informally on a visit by visit basis, but where amendments to the patient information leaflet/consent form occurs it might be appropriate to formally re-consent participants to the study. For example, during longitudinal research projects it might be wise to ask informally if participants are happy to continue their participation before commencing research activities. It is the Sponsors decision whether information update documentation only is provided to the participant with regards to the changes or whether formal re-consent is required. Re-consenting is appropriate if there is a significant change to a research project, or if there is new information which might alter an individual’s willing to participate in a research project.

29. WithdrawalSo why do participants choose to withdraw? • Participants may choose to withdraw from your study if they feel there are too many visits or invasive procedures involved. If the participant is fully informed of all aspects of the study this incidence can be minimised. • Experiencing adverse events may lead participants to withdraw from a study. Although researchers have no control over what events a participant experiences, they should provide reassurance and support to participants during an adverse event. • Participants may withdraw if the study medication/intervention means they have to change their existing medication regimes. • Participants may withdraw from a study if they feel their disease process is stable on current medication/treatment, or if they feel there is a lack of effect from the treatment they are receiving. • Participants can loose interest in taking part in the study, particularly if the study is being conducted over a long period of time. Efforts should be made to engage the participant and reiterate their importance in the study.

30. Withdrawal Process If a study participant does choose to withdraw there is a process which needs to be followed: There must be documentation of the withdrawal recorded in the medical notes, case report forms (where applicable) and the enrolment log must be completed (where applicable). Ensure you determine what portion of the study the participant is withdrawing from- e.g. this can be withdrawal from active treatment but agreement to follow up. NB- The participant does NOT have to give a reason or sign anything to withdraw. No further information can be gathered or retained past the point of withdrawal.

31. Completion Documentation of a participants study completion must be recorded in their medical notes and Case Report Form. The enrolment log must also be completed. (where applicable) Participants should always be thanked for their contribution and given details of how the study results can be obtained.

32. Question… If a participant withdraws from a study, is it appropriate to access their medical notes post withdrawal to obtain end point data? e.g. Further MI, date of death or disease progression.

33. Different Approaches to Consent • You may be faced with a situation where gaining Informed Consent is not a straight forward process and you need to adopt a different approach to obtaining consent: • Vulnerable Groups • Incapacitated Adults • Minors

34. Vulnerable Groups Minors & Incapacitated Adults • When dealing with vulnerable groups there are a number of points to be aware of: • They require special protection when being included in study • They should not be included in clinical trials if same results can be obtained using persons who are capable of giving consent • There should be an expected benefit to the participant • Trial should relate to condition which that group suffers from • As with all participants no incentives or financial inducements should be used

35. Minorsin Clinical Research In the UK there are 2 legal systems running in parallel with regards to consenting minors to research studies: CTIMPS NON-CTIMPS There is no legal age for minors when consenting to Non-CTIMPS studies. A competency criteria is used however this should not be used to consent minors below the age of 10. A minor is defined as under the age of 16 and consent from a parent or legal representative is required as stipulated in the Medicines for Human Use (Clinical Trials) Regulations 2004.

36. Minors in Clinical Research A hierarchy of consent must used this consists of: The parent or person with parental responsibility in law. A personal legal representative (a person not connected with the study, who is suitable by virtue of their relationship with the minor). Professional Legal Representative (a person not connected with the study, who is either the doctor primarily responsible for the medical treatment of the minor or a person nominated by the relevant healthcare provider NHS Trust).

37. Minors in Clinical Research Points to consider: The explicit wish of the minor must be considered All information must be given according to the capacity of the minor. Consent must represent presumed will of the minor It is recommended that additional training is undertaken by researchers who will be obtaining informed consent from minors. Additional training can be accessed via the NIHR website.

38. Question… A 13 year old boy attends for a routine hearing test appointment with his Aunt. (His parents are at work) He is potentially suitable to participate in a trial looking at a new audio device. What would you do? Ask the Aunt to sign the consent form? Ask the audiologist to sign the consent form? As this is not an emergency, wait for parents to be available to sign the consent form? Ask the minor to sign the consent form?

39. Incapacitated Adults (temporary & permanent) in Clinical Research In the UK there are 2 legal systems running in parallel with regards to consenting incapacitated adults to research studies CTIMPS NON-CTIMPS Clinical Trials of Investigational Medicinal Product Studies are governed by the Medicines for Human Use (Clinical Trials) Regulations 2004 All other studies not involving an Investigational Medicinal Product are governed by the Mental Capacity Act 2005

40. Incapacitated Adults in Clinical Research A hierarchy of consent must used. This would consist of a Personal Legal Representative (a person not connected with the study, who is suitable by virtue of their relationship with the adult). A Professional Legal Representative (a person not connected with the study, who is either the doctor primarily responsible for the medical treatment of the adult or a person nominated by the relevant healthcare provider NHS Trust. For adults with temporary incapacity it is essential that fully informed written consent is obtained from the participant once capacity is regained.

41. Incapacitated Adults in Clinical Research The explicit wish of the adult must be considered Information must be given according to capacity Consent must represent presumed will of the adult If the participant regains their capacity, fully informed written consent must be obtained It is recommended that additional training is undertaken by researchers who will be obtaining informed consent from adults lacking capacity. Additional training can be accessed via the NIHR website.

42. Question… An unconscious cardiac patient is eligible for a trial involving a new anti clotting drug. A personal legal representative cannot be located in time. What would you do? Utilise a professional legal representative? Administer the drug and then seek consent? Do nothing Once the patient regains consciousness do you need to re consent them? YES

43. Assent followed by Consent in an emergency situation for patients with capacity A critically ill patient with a life threatening condition when they present to hospital is possibly suitable to participate in a clinical trial, but due to time constraints and their current condition, obtaining written consent is not appropriate. Assent is a documented verbal consent, following a brief explanation of the study. Fully informed written consent should be sought as soon as practicable. If this is not obtained the patient should be withdrawn from the study.

44. Assent followed by Consent in an emergency situation for patients with capacity • Emergency admission but suitable to participate: A critically ill patient with a potentially life threatening condition presenting to hospital is possibly suitable to participate in a clinical trial. There would not be time for the written informed consent process to be undertaken. A process of verbal assent followed by written consent can be utilised. This process must be carried out in accordance with the procedure agreed by the REC. • Verbal assent following brief study outline: Assent is a documented verbal consent, following a brief explanation of the study. This must be documented in the participants medical notes and details of the person obtaining assent recorded in the trials master/investigator site file. • Participant has recovered sufficiently to make decision on participant: Once the patient has recovered sufficiently the written consent process must be followed. • Written Informed Consent:Fully informed written consent should be sought as soon as practicable. NB. The exact timeframe for written consent to be obtained will be outlined in the original ethics application and must be adhered to. If written consent is not obtained the patient should be withdrawn from the study. It is the researchers responsibility to ensure that written consent is obtained. The assent/consent process must be documented within the medical notes as evidence that the process has been adhered to. The use of assent followed by consent must have been stated in the original ethics application and must have received a favourable opinion from the REC.

45. Question…. A patient who gave assent for a study subsequently died before written informed consent was obtained. What data can you utilise in this situation?

46. UHL Audit Findings Inadequate permission for access to study records/notes for research team, sponsor, UHL Trust and/or regulatory authorities. Dates, subject’s initials and names written into consent forms by the consenting investigator, not the patient. Ticks instead of initials. Forms destroyed after sample analysis. Forms missing. New versions of the PIL being used prior to REC/R & D approval. Old versions being used after approval. No researcher or patient signature. Consent taken by people not approved to do so. Consent being taken before the REC agreed time to consider the study

47. Implications of not gaining Informed Consent The rights, safety and wellbeing of the patients may be compromised Data and samples will be destroyed Waste of time and resources Reputation affected Integrity of data collected The subject can sue Indemnity may be invalid Ethics/Trust approval may be withdrawn Future proposals may not be supported Inspection/Audit requirements may not be met.

48. TO SUMMARISE….. What? Why? How? What if?

49. Consent Assessment Please complete name on form and date of training session(not date assessment completed) Send by post or email to RITraining@uhl-tr.nhs.uk If sending by post please take photocopy Training certificates will be issued within two weeks of receipt. Should you fail, you will be given guidance on areas that were incorrect and asked to resubmit an assessment. Should you fail a second time you will be required to retake the training session.

50. USEFUL LINKS UHL R & I Department Web: www.leicestersresearch.nhs.uk Twitter: @LeicResearch University of Leicesterhttps://le.ac.uk UKCRC Regulatory & Governance Advice Servicehttp://www.ukcrc.org/regulationgovernance/rgadviceservice/ MHRA Clinical Trials Helplinectdhelpline@mhra.gsi.gov.uk Regulatory Agencies Medicines and Healthcare products Regulatory Agencyhttp://www.mhra.gov.uk