Informed Consent Documents Dr. Prerana.pptx

Informed Consent Documents are a crucial part of clinical trials. An in depth understanding of same will pave way for better Clinical research

1. INFORMED CONSENT DOCUMENTS Dr. Prerana Kadam (JR-1) Guide: Dr. Smita Tiwari Dr. Prerana Manik Kadam 1

2. History Introduction Purpose Process What is informed consent form? Elements of informed consent Special cases E lectronic consent Challenges with informed consent CONTENTS Dr. Prerana Manik Kadam 2

3. HISTORY The term “Informed consent” emerged only in the 1950s Informed consent  is a technical term first used by attorney, Paul G. Gebhard, in a medical malpractice United States court case in 1957 . Notable historical cases of research abuse have influenced the development and regulation of informed consent processes. The discovery of unethical research and the resulting public outcry over the years contributed to the institution of informed consent policies in research. Walter Reed authored these informed consent documents in 1900 for his research on yellow fever [6] Spanish English Dr. Prerana Manik Kadam 3

4. 1947: Nuremberg Medical Tribunal : - Found 16 individuals guilty of abuses -Medical research involving Nazi human experimentation. -Resulted in the 1947 establishment of the Nuremberg Code. -Stresses the necessity of informed consent to research. 1932 until 1972 Syphilis Study conducted in Tuskegee, Alabama: - Participants were left untreated for syphilis infections Despite the availability of penicillin, for observation of natural progression of disease -Informed consent was not obtained - Participants voluntarily elected - But were not informed of the availability of treatment -Were not made aware of the risks of lack of treatment Dr. Prerana Manik Kadam 4

5. 1946 to 1948: Public Health Service study in Guatemala, because of this Patient Autonomy was imbibed in informed consent form. 1964: World medical association Declaration of Helsinki -emphasizes the centrality of informed consent in research process. Dr. Prerana Manik Kadam 5

6. 1974 : National Research Act -Establishes National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research -Provided guidance for ethical human subjects research. 1979: Belmont Report -Written by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research . -The rights are protected through the use of 3 ethical principles: Dr. Prerana Manik Kadam 6

7. 1982: Council for International Organizations of Medical Sciences - Published International Ethical Guidelines for Biomedical Research Involving Human Subjects (revised in 1993 and 2002) -It stressed on the importance of informed consent process and its subsequent addition in research. Dr. Prerana Manik Kadam 7

8. Informed Consent is a process Health care provider discloses appropriate information to a patient So that the patient may make a voluntary choice to accept or refuse treatment. INTRODUCTION Informed Consent is important for protection of autonomy, confidentiality, rights and decision making process of the patients. INFORMED CONSENT Informed consent is defined by the ICH for GCP “ A process by which a subject voluntarily confirms his or her willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate” Dr. Prerana Manik Kadam 8

9. Informed consent is documented by means of a written, signed* and dated informed consent form. NEW DRUG AND CLINICAL TRIAL REGISTRY (NDCTR) 2019 Written Informed consent - Obtained from each study subject - Freely given - Complete verbal consent as well as using a patient information sheet - In a nontechnical and understandable language Audio-video recording of the informed consent process - Vulnerable subjects - Trials of New Chemical Entity or New Molecular Entity - Providing information to the subject and his understanding - Shall be maintained by the investigator for record: Waiver: - only audio recording of the informed consent process consent shall be maintained by the investigator for record. - clinical trial of anti-HIV and anti-leprosy drugs THIRD SCHEDULE (rules 8, 10, 11, 25, 35, 42 and 49) Point 2 (a, b & g) Dr. Prerana Manik Kadam 9

10. INFORMED CONSENT Dr. Prerana Manik Kadam 10

11. “ The goal of the informed consent process is to provide people with sufficient information so they can make informed choices about whether to begin or continue participation in clinical research” PURPOSE The main purpose of the informed consent process is to protect the patient . -A consent form is a legal document that ensures an ongoing communication process between you and your health care provider. It implies: -Health care provider has given information about the condition and treatment options. -The subject has used this information to choose the right option. Dr. Prerana Manik Kadam 11

12. P R O C E S S Dr. Prerana Manik Kadam 12

13. PROCESS Dr. Prerana Manik Kadam 13

14. An  informed consent document  is typically used to provide subjects with the information they need to make a decision to volunteer for a research study.   It provides the framework for information (i.e., the " elements ") that must be included as part of the consent process.  The consent document begins with a "concise and focused" presentation of  key information  that will help potential participants understand why they might or might not want to be a part of a research study.   WHAT IS INFORMED CONSENT FORM? Dr. Prerana Manik Kadam 14

15. Name of study, Purpose of the study Study number, Subject Identifier ESSENTIAL ELEMENTS Patient details Nominee / Legal heir details Description of: procedures to be followed, foreseeable risks, any benefits (Y/N), appropriate alternative medical & physiotherapies. Confidentiality record Dr. Prerana Manik Kadam 15

16. Confidentiality details Statement that participation is voluntary Contact details Sign copy of ICF Dr. Prerana Manik Kadam 16

17. (i) Title , nature and purpose of the research. (ii) Expected duration (iii) Description of the procedures to be followed including all invasive procedures, research methods used such as randomization & placebo controls (iv) Description of any reasonably foreseeable risks or discomforts. (v) Description of any benefit or no benefit (vi) Appropriate alternative procedures or therapies (vii) Confidentiality of records , who will have access to Subjects medical records. (viii) Trial treatment schedule ,probability for random assignment (ix) Financial compensation and the medical management as under: (a) Injury during the clinical trial, free medical management shall be given as long as required or till such time it is established that the injury is not related to the clinical trial, whichever is earlier. (b)Trial related injury or death, provide financial compensation for the injury or death. ELEMENTS OF INFORMED CONSENT FORM Dr. Prerana Manik Kadam 17

18. (x)Contact detail in case of queries (xi) The anticipated prorated payment, if any (xii) Responsibilities of subject (xiii) Statement that participation is voluntary, that the subject can withdraw from the study at any time and that refusal to participate will not involve any penalty or loss of benefits to which the subject is otherwise entitled. (xiv) Statement that there is a possibility of failure of investigational product to provide intended therapeutic effect. (xv) Statement that in the case of placebo controlled trial, the placebo administered to the subjects shall not have any therapeutic effect. (xvi) Any other pertinent information. (xvii)Approximate number of Subjects enrolled in the study ELEMENTS OF INFORMED CONSENT FORM Dr. Prerana Manik Kadam 18

19. Informed consent documents for clinical studies should disclose all reasonably foreseeable risks and benefits. Risks and benefits should be clearly communicated to the subject well in advance. Dr. Prerana Manik Kadam 19

20. Ref: INDIAN COUNCIL OF MEDICAL RESEARCH 2017 Definition of  risk by Merriam -Webster Dictionary 1:  possibility of loss or injury  2:  someone or something that creates or suggests a hazard CATEGORIES OF RISK IN CLINICAL TRIAL Dr. Prerana Manik Kadam 20

21. COMPENSATION 1. In case of clinical trial related death: Compensation = (B x F x R) / 99.37 Where, B = Base amount (i.e. 8 lakhs) F = Factor depending on the age of the trial subject as per Annexure 1 (based on Workmen Compensation Act) R = Risk Factor depending on the seriousness and severity of the disease, presence of co-morbidity and duration of disease of the trial subject at the time of enrolment in the clinical trial between a scale of 0.5 to 4 However, in case of patients whose expected mortality is 90% or more within 30 days , a fixed amount of Rs. 2 lakhs should be given (a) In case of an injury occurring to the subject during the clinical trial, free medical management shall be given as long as required or till such time it is established that the injury is not related to the clinical trial, whichever is earlier. (b) In the event of a trial related injury or death , the sponsor or his representative or the investigator or centre, as the case may be, in accordance with the rule 39, as the case may be, shall provide financial compensation for the injury or death Chapter VI SEVENTH SCHEDULE ( rules 39, 40, and 42) Dr. Prerana Manik Kadam 21

22. 2. In case of clinical trial related injury (other than death): Quantum of compensation for SAE should not exceed quantum of compensation for death. A permanent disability Congenital anomaly or birth defect Dr. Prerana Manik Kadam 22

23. In case of A permanent disability: In case of SAE causing permanent disability to the trial subject, the quantum of compensation in case of 100% disability shall be 90% of the compensation which would have been due for payment to the nominee (s) in case of death of the trial subject. The quantum for less than 100% disability will be proportional to the actual percentage disability the trial subject has suffered. Accordingly, following formula shall be applicable for determination of compensation: Compensation = (C x D x 90) / (100 x 100) Where : D = Percentage disability the trial subject has suffered. C = Quantum of Compensation which would have been due for payment to the trial subject's nominees) in case of death of the trial subject. Dr. Prerana Manik Kadam 23

24. (ii) In case of Congenital anomaly or birth defect: The congenital anomaly or birth defect in a baby may occur due to participation of anyone or both the parent in clinical trial. Following situations may arise due to congenital anomaly or birth defect. (a) Still birth; (b) Early death due to anomaly; (c) No death but deformity which can be fully corrected through appropriate intervention; (d) Permanent disability (mental or physical). The compensation -a lump sum amount -fixed deposit or alike, it shall bring a monthly interest amount -approximately equivalent to half of minimum wage of the unskilled worker. -The quantum of compensation in such cases of SAE shall be half of the base amount as per formula for determining the compensation for SAE resulting into death. In case of birth defect leading to sub-clause (c) and (d) of this clause to any child, the medical management as long as required shall be provided by the Sponsor or his representative which will be over and above the financial compensation. Dr. Prerana Manik Kadam 24

25. (iii) Chronic life-threatening disease; and (iv) Reversible SAE in case it is resolved. Accordingly, following formula shall be applicable for determination of compensation: Compensation = 2 X W X N. Where, W = Minimum wage per day of the unskilled worker N = Number of days of hospitalization Dr. Prerana Manik Kadam 25

26. SPECIAL CASES Case 1 : Children Case 2 : Illiterate person Case 3 : Unable to give informed consent Case 4 : Vulnerable population Case 5 : Pregnant women Case 6 : Non english speaking person Case 7 : Covid-19 Pandemic Dr. Prerana Manik Kadam 26

27. CASE 1 : CHILDREN No decision-making capacity P arents or other surrogate decision-makers give informed consent for diagnosis , treatment and participation in clinical trials. Assent A child’s affirmative agreement to be a participant in research. T erm used to express willingness to participate in research B y person who are too young to give informed consent Old enough to understand in general, the research, its expected risks and possible benefits, and the activities expected of them as subjects. [45 CFR 46(sub part D)] Dr. Prerana Manik Kadam 27

28. CASE 1 : CHILDREN 0-7 Years Parent, guardian, 7-12 Years Parent, guardian & verbal assent 13-17 Years written assent required Dr. Prerana Manik Kadam 28

29. 0-7 Years Parent, guardian 7-12 Years Parent, guardian & verbal assent 13-17 Years Parent guardian consent written assent required Parent Yes Child Yes Parent Yes Child No Parent, guardian Parent, guardian Parent, guardian & verbal assent Court-ordered appointment of a guardian Parent guardian consent written assent required Court-ordered appointment of a guardian Dr. Prerana Manik Kadam 29

30. The potential subject must be able to place a sign/thumb impression on the consent form after understanding the clinical trial. After that the subject must also be able to: 1.Comprehend the concepts of the study and understand the risks and benefits of the study as it is explained verbally, and 2. Be able to indicate approval or disapproval for study enrolment. Who will confirm the above facts? NDCTR Third schedule 2(d) If the trial subject his or her legally acceptable representative is unable to read or write an impartial witness should be present during the entire informed consent process who must append his or her signature to the consent form. CASE 2 : ILLITERATE PERSON [45 CFR 46.117] Dr. Prerana Manik Kadam 30

31. CASE 3 : UNABLE TO GIVE INFORMED CONSENT Unconscious person Suffering from severe mental illness / disability Written informed consent obtained from a legally acceptable representative (LAR) NDCTR Third schedule 2(c) LAR is a person who is able to give consent for or authorize and intervention in the patient as provided by the law of India) Dr. Prerana Manik Kadam 31

32. Persons who are relatively or absolutely incapable of protecting their own interests are termed as Vulnerable Research Population. (ICH,GCP 4.8.10) Group/individuals that cannot give informed consent because of limited autonomy (e.g, children, mentally ill and prisoners) Also refers to subjects who may be unduly influenced to participate (e.g, students, subordinates and patients. Persons with – incurable diseases, – in custody, – unemployed or needy, – in emergency rooms, – homeless persons, – wanderers, any ethnic or racial minority groups should be considered as dangerous population whose mode of consent should be carefully considered and approved by the Ethics Committee. For such populations, full committee meeting is a must. Ethics Committee, IRB are responsible for protecting the rights of such population in any clinical trial. CASE 4 : VULNERABLE POPULATION Dr. Prerana Manik Kadam 32

33. Researchers should obtain informed consent from both the pregnant woman and the father, provision of two signatures to be made in the consent form. Consent of the father is not necessary if… The purpose of the study is to meet the health needs of the mother. 2. The identity or where about of the father can not be reasonably ascertained. CASE 5 : PREGNANT WOMEN [45 CFR 46 (sub part B)] Dr. Prerana Manik Kadam 33

34. CASE 6 : NON ENGLISH SPEAKING PERSON [45 CFR 46.116] Ideal is to use consent translated to participant’s native language a)If it a major Indian language -Certified of professional translator used to translate the consent form -Copy of consent form to be attached to the protocol pre approved by ethics committee. b) In case of foreign language -Impartial witnes s required in this case 2. A copy of the consent document must be given to each subject. 3.While a translator may be helpful in facilitating conversation with a non-English speaking subject, verbal translation of the consent. Dr. Prerana Manik Kadam 34

35. CASE 7 : COVID-19 PANDEMIC - If obtaining Informed consents becomes difficult, plan alternative mechanisms (4.2 – Electronic IC +pt digital signal allowed) -Additional safeguard to protect participants to be considered (4.1.4 –Broad IC +opt out/clin samples) -Roles of researchers, caregivers and volunteer workers must always be clarified, address COI (5.3 – HCW-Spon responsible for their safety) -Ensure that there is no inducement, special protection of orphaned. (vulnerable++) -Consider waivers for consent.( ano / surv / emer ) Dr. Prerana Manik Kadam 35

36. These are electronic processes that use various, and possibly multiple, electronic formats such as text, graphics, audio, video, podcasts or interactive websites to explain information related to a study and to document informed assent/consent from a participant or LAR. The process, electronic materials, method of documentation (including electronic/ digital signatures), methods used to maintain privacy of participants, confidentiality, and security of the information as well as data use policies at the research site must be reviewed and approved by the EC In addition to electronic consent, if required a paper/soft copy of the document is needed for archiving and a paper/soft copy is also given to the participant. Interactive formats, if used, should be simple to navigate. Electronic methods should not be used if participants, for any reason, indicate a lack of comfort with electronic media. ELECTRONIC CONSENT Dr. Prerana Manik Kadam 36

37. The researcher can apply to the EC for a waiver of consent if the research involves less than minimal risk to participants and the waiver will not adversely affect the rights and welfare of the participants The EC may grant consent waiver in the following situations: [45 CFR 46.116 c,d] • Research cannot practically be carried out without the waiver and the waiver is scientifically justified; • Retrospective studies, where the participants are de-identified or cannot be contacted; • Research on anonymized biological samples/data; • Certain types of public health studies/surveillance programmes/programme evaluation studies; • Research on data available in the public domain; or • Research during humanitarian emergencies and disasters, when the participant may not be in a position to give consent. Attempt should be made to obtain the participant’s consent at the earliest In most cases, investigators are expected to obtain a signature from the participant on a written informed consent document (i.e., to document the consent to participate) unless the IRB has waived the consent requirement or documentation (signature) requirement WAIVER OF CONSENT Dr. Prerana Manik Kadam 37

38. Challenges with Informed Consent Problems Physicians may face Use of technical language b. Uncertainties intrinsic to all medical information c. Worried about harming or alarming the patient d. Hurried and pressed by multiple duties Problems Patients may face Limited knowledge b. May be inattentive or distracted c. Overcome by fear and anxiety d. Selective hearing because of denial, fear, or preoccupation with illness Dr. Prerana Manik Kadam 38

39. 15* CONCLUSION 39 Informed consent is not just a document but a continous process. It must be approved prior to the commencement of the study by IRB /Ethics committee. It protects the patient autonomy and ensures safeguarding of patient’s and investigator’s beneficence and rights. It should be personalized according to the special consideration related to the trial subjects like children , pregnant women etc. Dr. Prerana Manik Kadam

40. REFERENCES Singh, N., Madkaikar , N. J., Gokhale , P. M., & Parmar , D. V. (2020). New drugs and clinical trials rules 2019: Changes in responsibilities of the ethics committee.  Perspectives in clinical research ,  11 (1), 37–43. https://doi.org/10.4103/picr.PICR_208_19 Mathur , R., & Swaminathan , S. (2018). National ethical guidelines for biomedical & health research involving human participants, 2017: A commentary.  The Indian journal of medical research ,  148 (3), 279. Junod , Valérie (2005). Clinical drug trials Studying the safety and efficacy of new pharmaceuticals. Genève: Schulthess . p. 545. Faden , Ruth R.; Beauchamp, Tom L.; King, Nancy M.P. (1986). A history and theory of informed consent (Online ed.). New York: Oxford University Press. ISBN978-0-19-5036862. Masic , Izet & Hodzic , Ajla & Mulic , Smaila . (2014). Ethics in Medical Research and Cambridge Quarterly of Healthcare Ethics  ,  Volume 20  ,  Issue 4  , October 2011 , pp. 515 – 523 DOI: https://doi.org/10.1017/S0963180111000259 Laura Cutter, MA, MLIS, (2016 )Walter Reed, Yellow Fever, and Informed Consent,  Military Medicine , Volume 181, Issue 1, January, Pages 90–91, https://doi.org/10.7205/MILMED-D-15-00430  "UN Treaty Collection - International Covenant on Civil and Political Rights". Status of ratification  Publication. International Journal of Preventive Medicine. 5. 1073-1082. Nijhawan LP, Janodia MD, Muddukrishna BS, et al. (2013); Informed consent: Issues and challenges. J Adv Pharm Technol Res. 4(3):134-140. doi:10.4103/2231-4040.116779 Dr. Prerana Manik Kadam 40

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