Question

Review the PILOT DOSE-RESPONSE STUDY OF MEMOROL Consent Form (ICF) against the ‘Informed Consent Form Checklist’. Checking to determine whether the required ICH-GCP elements are present by checking Yes or NoI If you review an element and are not convinced that the ICF adequately covers the details– indicate this on the review form by making a note in the “comments section.

”PILOT DOSE-RESPONSE STUDY OF MEMOROL

IN AGE-ASSOCIATED MEMORY IMPAIRMENT

                                                 CONSENT FORM

Dr Frank N Stein, Have Mercy Medical Centre

Introduction: I have been asked to participate in a 1 month research study which will evaluate the effectiveness and safety of three dosage levels of a new drug called “Memorol” in the treatment of age associated memory impairment.  The scope of the study is such that a total of 160 patients will be studied across three medical centers.

Either one of three dose levels (low, medium, or high) of “Memorol” or placebo (a pill with no medication in it) will be administered to me over the 1 month time period.  I will not be told whether I am receiving real medication (Memorol) or placebo. The medication “Memorol” is currently approved by the Food and Drug Administration and is routinely used to treat people who have high blood pressure.  However for this particular study, “Memorol” is being studied for the specific treatment of age-associated memory impairment.  The dosages of “Memorol” used for this study have been carefully adjusted (lowered) so that the lowering of blood pressure will be either slight or nonexistent (for normal subjects).

I will be seen at least once every week during the one-month program.  During that time I will be prompted for medical history, undergo two physical exams, a chest x-ray, CT scan (an x-ray of the head) and various vital sign readings (blood pressure).  All of this will serve to test the safety aspect of “Memorol”.  I understand that I will also be subjected to a comprehensive battery of computerized and non-computerized mental testing so that study personnel can assess the effectiveness of “Memorol”.  As more and more subjects in the study receive this drug over time, any new findings that show an evident increased risk will be revealed to me.  I understand that this might affect my willingness to continue participation in the clinical trial.

Risks, Inconveniences and discomforts:In order to establish the fact that I have age-associated memory impairment, I understand that I will undergo a moderately vigorous battery of mental testing, which may prove to be discomforting.  When my blood is drawn for laboratory tests, I may experience some discomfort and/or bruising at the site.  Also, I understand that some of the common side effects of “Memorol” include headache, nausea, dry mouth, lightheadedness, tiredness, indigestion, constipation, diarrhea and muscle cramps.  As with all medications or procedures, there may be risks that are simply not known. At any point during this 1-month clinical study, I understand that I can exercise my right to discontinue participation in the trial.

Benefits:The major benefit I will receive from this study is a contribution to medical knowledge about the impact of drug treatment on age-associated memory impairment.  I recognize that no therapeutic benefit can be guaranteed.

Alternative Therapy:If I choose to exercise my right to discontinue my participation in the “Memorol” clinical trial or if the risk(s) becomes unacceptably high, the investigator (doctor) treating me will suggest alternative medication (alpha agonists) that might be effective in combating age-associated memory impairment.  At my investigator’s recommendation, and at my option, I will decide whether or not to try an alternative medication.

Cost of Participation: During the study, all laboratory tests, clinical evaluations and medications will be provided a no cost to me.  I will receive $60.00 for each completed study visit, up to a maximum of $300.00, if all required visits are made over the entire 1-month study period.

These weekly payments are intended to reimburse me for miscellaneous expenses that I might encounter as a result of being in the clinical study (public transportation, baby sitter fees, etc.).

Pregnancy (if applicable) If I am pregnant or contemplating pregnancy, I will not be a candidate for this study.  If I am of child bearing potential, I am presently using a medically accepted form of birth control.  The medication used in this study may involve risks, which are currently unforeseen, to me or to my unborn child if I am now, or if I become pregnant at any time during the study.

Research Related Injury: I understand that in the event of any physical or mental injury resulting from my participation in this study, the Have Mercy Medical Centerwill not offer any compensation. However, medical treatment for injury due to my participation in this study shall be made available primarily through the investigator and the sponsor will provide associated costs. No other compensation (injuries that occur that are not medication related) will be made available.

Confidentiality of Records: The information in my records will be kept confidential.  My medical records may be reviewed by representatives from the medical research department of Pharmaceutical Research Associates and/or Food and Drug Administration representatives with

Confidentiality being maintained.  Results of my treatment may be published for scientific purposes if my identity is not revealed.

Withdrawal:My participation this study is voluntary.  I may withdraw at anytime without prejudicing my future medical care. I am aware that my voluntary withdrawal will not introduce any obvious risk. I realize that there may be certain circumstances where the investigator may feel that it would be in my best interest to be terminated from the study.  I realize that the investigator can exercise this discretion without my concurrence.

I have read and understand the information in this consent form and have had the opportunity to question the investigator about this study.  I will be given a copy of this consent form for my records.  I hereby willingly give my consent to participate in this study.

If I have any questions concerning the study or in the event of an emergency while participating in the study, I can contact:

Frank N. Stein, M.D., Investigator     1-(800)-321-5629 (24-hour, toll free)

Have Mercy Medical Center

1300 Tombstone Boulevard

Death Valley, CA 94134

If, for whatever reason, I have any questions concerning my right as a research participant in this clinical trial, I can contact the following impartial 3^rdparty individual:

John Q. Reynolds, M.D., IRB Chairman   1-(800)-321-9536 (24-hour, toll free)

Have Mercy Medical Center

1300 Tombstone Boulevard

Death Valley, CA 94134

Patient Signature ____________________________ Date______________

Person who conducted the informed consent discussion:

Signature ___________________________________ Date______________

INFORMED CONSENT FORM CHECKLIST. Yes NO Comment

ICH-GCP 4.8.10 m	That the subject’s participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.
ICH-GCP 4.8.10 n	That the monitor(s), the auditor(s), the IEC/IRB, and the regulatory authority(ies) will be granted direct access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject's legally acceptable representative authorities such access.
ICH-GCP 4.8.10 o	That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the subject's identity will remain confidential.
ICH-GCP 4.8.10 p	That the subject or the subject's legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the subject's willingness to continuing participation in the trial.
ICH-GCP 4.8.10 q	The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to contact in the event of trial-related injury.
ICH-GCP 4.8.10 r	The foreseeable circumstances and/or reasons for which the subject's participation in the trial will be terminated.
ICH-GCP 4.8.10 s	The expected duration of the subject's participation in the trial.
ICH-GCP 4.8.10 t	The approximate number of subjects involved in the trial.

Answer 1

		Yes	No	Comment
ICH-GCP 4.8.10 m	That the subject’s participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled.		No	There is mention of voluntary participation and right to withdraw from study at any time but ability of subjects to give consent is questionable. Study is evaluating effect of a drug Memorol in the treatment of age associated memory impairment. So the subjects are having memory impairment and are vulnerable . Subject may legal capacity to give consent but his psychological capacities are questionable -Whether the participant is able to retain, weigh and use the information provided for making decision. Participant may have diminished capacity to consider and protect his own interests. That need to be assessed first, and depending on results consent from a legally acceptable representative may be required. This is not mentioned in the study.
ICH-GCP 4.8.10 n	That the monitor(s), the auditor(s), the IEC/IRB, and the regulatory authority(ies) will be granted direct access to the subject's original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject's legally acceptable representative authorities such access.		No	It is mentioned that by representatives from the medical research department of Pharmaceutical Research Associates and/or Food and Drug Administration representatives with confidentiality being maintained, but the purpose of such reviews is not mentioned and
ICH-GCP 4.8.10 o	That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the subject's identity will remain confidential.	Yes		There is mention of maintaining confidentiality of information.
ICH-GCP 4.8.10 p	That the subject or the subject's legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the subject's willingness to continuing participation in the trial.	Yes		It is mentioned that as more information will emerge about the evident risk to subjects it will be revealed.
ICH-GCP 4.8.10 q	The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to contact in the event of trial-related injury.	Yes		It is mentioned to contact Frank N. Stein, M.D foe any and questions related to study and V. Participants can contact Mr. John Q. Reynolds for any queries regarding their rights as research participant during the proposed trial. Complete address and phone numbers of both are mentioned.
ICH-GCP 4.8.10 r	The foreseeable circumstances and/or reasons for which the subject's participation in the trial will be terminated.	Yes		It is mentioned that subject may willingly withdraw from the study during any time during the study, as well as researcher may do it on their discretion if it is in best interest of the participants.
ICH-GCP 4.8.10 s	The expected duration of the subject's participation in the trial.	Yes		It is mentioned that expected duration of trial will be 1 month.
ICH-GCP 4.8.10 t	The approximate number of subjects involved in the tri	Yes		It is revealed that there will be total 160 participants in the study.