180416P - THE INVESTIGATOR

Paper prepared by Professor Omar Hasan Kasule Sr. MB ChB (MUK), MPH (Harvard), DrPH (Harvard) Professor of Epidemiology at King Fahad Medical City Riyadh

Investigator's Qualifications and Agreements:

• The investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial

• The  investigator  should  be  thoroughly  familiar  with  the  appropriate  use  of  the investigational product.

• The investigator should be aware of, and should comply with, GCP and the applicable regulatory requirements.

• The investigator/institution should permit monitoring and auditing by the sponsor, and inspection by the appropriate regulatory authority(ies).

• The investigator should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties.

Adequate Resources -1:

• The investigator should be able to demonstrate a potential for recruiting the required number of suitable subjects within the agreed recruitment period.

• The investigator should have sufficient time to properly conduct and complete the trial within the agreed trial period.

• The  investigator  should  have  available  an  adequate  number  of  qualified  staff  and adequate facilities for the foreseen duration of the trial to conduct the trial properly and safely.

• The investigator should ensure that all persons assisting with the trial are adequately informed about the protocol, the investigational product(s), and their trial-related duties and functions.

Adequate Resources –2 addendum:

• The investigator is responsible for supervising any individual or party to whom the investigator delegates trial-related duties and functions conducted at the trial site.

• The investigator/institution can retain the services of any qualified individual or party to perform trial-related duties and functions

Medical Care of Trial Subjects:

• A qualified physician  who is an investigator or a sub- investigator for the trial, should be responsible for all trial-related medical  decisions.

• During and following a subject's participation in a trial, the investigator should ensure that adequate medical care is provided to a subject for any adverse events.

• It is recommended that the investigator inform the subject's primary physician about the subject's participation in the trial if the subject agrees to the primary physician being informed.

• Although a subject is not obliged to give his/her reason(s) for withdrawing prematurely from a trial, the investigator should make a reasonable effort to ascertain the reason(s), while fully respecting the subject's rights.

Communication with IRB:

• Before  initiating  a  trial,  the  investigator/institution  should  have  written  and  dated approval/favorable opinion from the IRB for the trial protocol, written informed consent  form,  and other relevant documents

• The investigator should provide the IRB with a current copy of the Investigator's Brochure. 

Compliance with Protocol:

• The investigator/institution should conduct the trial in compliance with the protocol agreed to by the sponsor and which was given approval/favorable opinion by the IRB

• The investigator should not implement any deviation from, or changes of the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the IRB.

• The investigator should document and explain any deviation from the approved protocol and report to IRB.

Investigational Product(s):

• Responsibility for investigational product(s) accountability at the trial site(s) rests with the investigator.

• The investigator should maintain records of the product's delivery to the trial site, the inventory at the site, the use by each subject, and then return to the sponsor or alternative disposition of unused product(s). 

• The investigational product(s) should be stored as specified by the sponsor and in accordance with applicable regulatory requirement(s).

• The  investigator  should  ensure  that  the  investigational  product(s)  are  used  only  in accordance with the approved protocol.

• The investigator should explain the correct use of the investigational product(s) to each subject and should check, at intervals appropriate for the trial, that each subject is following the instructions properly.

Randomization Procedures and Unblinding:

• The investigator should follow the trial's randomization procedures, if any, and should ensure that  the  code  is  broken  only  in  accordance  with  the  protocol.  

• If  the  trial  is  blinded,  the investigator should promptly document and explain to the sponsor any premature unblinding (e.g., accidental unblinding, unblinding due to a serious adverse event) of the investigational product(s).

Informed Consent of Trial Subjects -1:

• Prior to the beginning of the trial, the investigator should have the IRB written approval/favorable opinion of the written informed consent form and any other written information to be provided to subjects.

• The written informed consent form and any other written information to be provided to subjects should be revised whenever important new information becomes available that may be relevant to the subject’s consent and IRB approval shall be obtained. 

• Neither the investigator nor the trial staff, should coerce or unduly influence a subject to participate or to continue to participate in a trial.

• There is no waiver of any legal rights that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence.

• The investigator should fully inform the subject of all pertinent aspects of the trial including the written information and the approval/favorable opinion by the IRB.

Informed Consent of Trial Subjects - 2:

• The language used in the consent should be as non-technical as practical and should be understandable to the subject

• Before informed consent may be obtained, the investigator should provide the subject ample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial should be answered to the satisfaction of the subject.

• Prior to a subject’s participation in the trial, the written informed consent form should be signed and personally dated by the subject or by the subject's legally acceptable representative, and by the person who conducted the informed consent discussion.

Information to be provided in the consent 1:

(a)  That the trial involves research. 

(b)  The purpose of the trial.

(c)  The trial treatment(s) and the probability for random assignment to each treatment. 

(d)  The trial procedures are to be followed, including all invasive procedures.

(e)  The subject's responsibilities.

(f)   Those aspects of the trial that are experimental.

(g) The reasonably foreseeable risks or inconveniences to the subject 

(h)  The reasonably expected benefits. 

(i)   The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks.

(j)   The compensation and/or treatment available to the subject in the event of trial-related injury.

Information to be provided in the consent 2:

(k)  The anticipated prorated payment, if any, to the subject for participating in the trial. (l)   The anticipated expenses, if any, to the subject for participating in the trial.

(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.

(n)  That the monitor(s), the auditor(s), the IRB/IEC, 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

Information to be provided in the consent 3:

(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.

(p)  That the subject will be informed in a  timely  manner  if  information  becomes  available  that  may  be  relevant  to  the subject's willingness to continue participation in the trial.

(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.

(r)   The foreseeable circumstances and/or reasons under which the subject's participation in the trial may be terminated.

(s)  The expected duration of the subject's participation in the trial. (t)   The approximate number of subjects involved in the trial.

Signing the consent:

• Prior to participation in the trial, the subject should receive a copy of the signed and dated written informed consent form 

• A legal representative may sign for the subject in certain circumstances

• A non-therapeutic trial (i.e., a trial in which there is no anticipated direct clinical benefit to the subject), should be conducted on subjects who personally give consent and who sign and date the written informed consent form.

Records and Reports 1:

• The investigator should maintain adequate and accurate source documents and trial records that include all pertinent observations on each of the site’s trial subjects. 

• The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the CRFs and in all required reports.

• Data reported on the CRF, that are derived from source documents, should be consistent with the source documents or the discrepancies should be explained.

• Any  change  or  correction  to  a  CRF  should  be  dated,  initialed,  and  explained  (if necessary) and should not obscure the original entry (i.e., an audit trail should be maintained); 

Records and Reports 2:

• The investigator should maintain the trial documents as specified in Essential Documents for the Conduct of a Clinical Trial.

• Essential documents should be retained until at least 2-years after the last approval of a marketing application.

• The financial aspects of the trial should be documented in an agreement between the sponsor and the investigator/institution.

• Upon request of the monitor,   auditor,   IRB,   or   regulatory   authority,   the investigator/institution should make available for direct access all requested trial-related records.

Progress Reports:

• The investigator should submit written summaries of the trial status to the IRB annually, or more frequently if requested by the IRB.

• The investigator should promptly provide written reports to the sponsor, the IRB, and, where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to subjects.

Safety Reporting:

• All serious adverse events (SAEs) should be reported immediately to the sponsor and IRB

• Adverse events and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol.

• For reported deaths, the investigator should supply the sponsor and the IRB/IEC with any additional requested information (e.g., autopsy reports and terminal medical reports).

Premature Termination or Suspension of a Trial:

• If the trial is prematurely terminated or suspended for any reason, the investigator should promptly inform the trial subjects, should assure appropriate therapy and follow-up for the subjects, and should inform the regulatory authority(ies). 

• If the investigator terminates or suspends a trial without the prior agreement of the sponsor, the investigator should inform the IRB, and should provide the sponsor and the IRB a detailed written explanation of the termination or suspension.

• If the sponsor terminates or suspends a trial the investigator should promptly inform the IRB and provide a detailed written explanation of the termination or suspension.

• If the IRB terminates or suspends its approval/favorable opinion of a trial, the investigator should inform the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension.

Final Report(s) by Investigator:

• Upon completion of the trial, the investigator should inform the IRB with a summary of the trial’s outcome, and the regulatory authority(ies) with any reports required.