Good Clinical Practice

Introduction

Not learn what is right,
but to practice what is right.

As an overview, Good Clinical Practice (GCP) is an international ethical and scientific quality standard of the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials involving the participation of human subjects.

  • Hence, GCP is ONLY NEEDED if you would like to be an investigator of a randomised controlled trial. In other words, if you are just planning to carry out a cross-sectional or retrospective study (not involving any intervention), GCP certificate is not needed.

As stated in Declaration of Helsinki, while the primary purpose of medical research is to generate new knowledge, this goal can never take precedence over the rights and interests of individual research subjects. In other words, among the two major aims of GCP

  • Patient safety is the most important of all
  • and only then followed by Scientific validity



Tripartite Guideline

Often, GCP is described as a tripartite guideline because it discusses the responsibilities of 3 parties

  • Independent review board
  • Sponsor
  • Investigator

Independent Review Board

  • Should include
    • At least 5 members.
    • At least 1 member whose primary area of interest is in a non-scientific area.
    • At least 1 member who is independent of the institution/trial site.
  • Responsibilities
    • Safeguard the rights, safety, and well-being of all trial subjects.
    • Review a proposed clinical trial within a reasonable time and document its view in writing.
    • Consider the qualifications of the investigator for the proposed trial.
    • Conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human subjects, but at least once a year.
    • Review both the amount and method of payment to subjects to assure that neither presents problems of coercion or undue influence on the trial subjects.
    • Ensure information regarding payment is set forth in the written informed consent form and any other written information to be provided to subjects.
  • Should retain all relevant records for a period of at least 3 years after completion of the trial and make them available upon request from the regulatory authority(ies).

Sponsor

  • The sponsor should implement a system to manage quality throughout all stages of the trial process.
    • Trial design
    • Data handling and record keeping
    • Investigator selection
    • Compensation to subjects and investigators
    • Notification/submission to regulatory authority(ies)
    • Confirmation of review by IRB/IEC
    • Manufacturing, packaging, labelling and coding investigational product(s)
    • Supplying and handling investigational product(s)
    • Record access
    • Safety information
    • Adverse drug reaction reporting
    • Trial monitoring
    • Perform audits by appointing independent third party
  • The sponsor may transfer any or all of the sponsor's trial-related duties and functions to a Contract Research Organization (CRO), but the ultimate responsibility for the quality and integrity of the trial data always resides with the sponsor.
  • The sponsor should submit to the regulatory authority(ies) all safety updates and periodic reports, as required by applicable regulatory requirement(s).
  • The sponsor should update the investigator's brochure as significant new information becomes available.
  • Should inform the investigator(s) in writing of the need for record retention and should notify the investigator(s) in writing when the trial related records are no longer needed.

Investigator

  • An investigator should be qualified by education, approved training in Good Clinical Practice, and experience to assume responsibility for the proper conduct of the trial. Hence, to become an investigator, you will need to attend a local GCP workshop and pass the examination.
  • A qualified physician (or dentist, when appropriate), who is an investigator or a subinvestigator for the trial, should be responsible for all trial-related medical (or dental) decisions.
  • The investigator should have adequate resources (e.g. potential for recruiting the required number of suitable subjects within the agreed recruitment period, sufficient time, sufficient persons assisting with the trial).
  • The investigator should maintain a list of appropriately qualified persons to whom the investigator has delegated significant trial-related duties.
  • Before initiating a trial, the investigator should have written and dated approval/favourable opinion from the IRB/IEC for the trial protocol, written informed consent form, consent form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided to subjects.
  • The investigator should conduct the trial in compliance with the protocol agreed to by the sponsor and if required, by the regulatory authority(ies) and which was given approval/favourable opinion by the IRB/IEC.
    • Storage and use of investigational product
    • Randomization and unblinding
    • Informed consent
  • The investigator/institution should maintain adequate and accurate source documents and trial records that include all pertinent observations on each of the site’s trial subjects. Source data should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source data should be traceable, should not obscure the original entry, and should be explained if necessary (e.g., via an audit trail).
  • The investigator should permit monitoring and auditing by the sponsor, and inspection by the appropriate regulatory authority(ies).
  • Promptly report to the IRB/IEC all deviations from the protocol, all adverse drug reactions that are both serious and unexpected and new information that may affect adversely the safety of the subjects or the conduct of the trial.
  • Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor.



Clinical Trial Exemption and Clinical Trial Import Licence

Clinical Trial Exemption (CTX) is an approval by the DCA authorizing the applicant to manufacture any local product for the purpose of clinical trial.

Clinical Trial Import Licence (CTIL) is a license in Form 4 in the schedule of The Control of Drugs and Cosmetics Regulations of 1984, authorizing the licensee to import any product for purposes of clinical trials, notwithstanding that the product is not a registered product.



Informed Consent

Informed consent is 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. Informed consent is documented by means of a written, signed and dated informed consent form.

  • If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to subjects, is read and explained to the subject or the subject’s legally acceptable representative, and after the subject or the subject’s legally acceptable representative has orally consented to the subject’s participation in the trial and, if capable of doing so, has signed and/or thumbprinted and dated the informed consent form, the witness should sign and personally date the consent form. By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and appropriately understood by, the subject or the subject’s legally acceptable representative, and that informed consent was freely given by the subject or the subject’s legally acceptable representative.

The language used in the oral and written information about the trial, including the written informed consent form, should be as nontechnical as practical and should be understandable to the subject or the subject's legally acceptable representative and the impartial witness, where applicable.

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. Any revised written informed consent form, and written information should receive the IRB/IEC's written approval/favourable opinion in advance of use. The subject or the subject's legally acceptable representative should be informed in a timely manner if new information becomes available that may be relevant to the subject's willingness to continue participation in the trial. The communication of this information should be documented.

Below is a video on the elements of a successful informed consent.

NOTE: Parental consent is required for minors below the age of 18 years old. Assent is required for respondents between 7 years old to 18 years old.



Adverse Drug Reaction Reporting

Adverse Event is any untoward medical occurrence in a patient of clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Adverse Drug Reaction is all noxious and unintended responses to a medicinal product related at any dose.

Serious = any untoward medical occurrence that at any dose:

  • results in death,
  • is life-threatening,
  • requires inpatient hospitalization or prolongation of existing hospitalization,
  • results in persistent or significant disability/incapacity, or
  • is a congenital anomaly/birth defect.

Reporting of Serious Unexpected ADRs need to be done

  • To sponsor within 24 hours and
  • To regulatory authorities within 7 days of awareness following death and life-threatening cases (followed by full report within 8 additional days) and within 15 days of awareness for other SUSAR.

If there is aggregate of adverse reactions from oversea, sponsor needs to report within 48 hours to Drug Control Authority.



Summary

Above are key points that I extracted from Malaysian Guideline for Good Clinical Practice, 2018. If there is any doubt, please check back the source document. All the relevant guidelines are available here.



External Links

Comments

Post a Comment