Difference between ICH-GCP, Indian GCP and Schedule Y
ICH-GCP vs Indian GCP
Good Clinical Practice (GCP)
is an international standard set for conducting, formulating, documenting, and
reporting clinical trials that may involve humans as participants. It is
important to comply with this standard since it provides the public the
assurance that the trial subjects’ rights, safety, and well-being are
protected, and that data from clinical trials are credible. The goal of
the ICH GCP (International Conference on Harmonization of Good Clinical
Practice) is to provide a uniform standard for U.S., European Union, and Japan
to facilitate the adoption of clinical data by regulatory authorities of the
said jurisdictions. The guidelines should be followed when data from clinical
trials should be submitted to regulatory authorities.
The
Indian version of GCP is based on the ICH-GCP, but there are key differences
between the two. Some of the guidelines found in the Indian version result in
the difficult methodology which becomes overwhelming for sponsors and
investigators.
SOPs from investigator and
sponsors are at issue. The Indian guidelines state that the copy for
the SOPs must be duly signed by both the investigator and the
sponsor. The investigator, with his research team, should comply with the SOPs.
This may be impossible since it will become a huge burden for sponsors to get
the SOPs signed by all the investigators of the trial. The entire process of
maintaining several SOPs and making revisions are complex enough.
The
role of the investigator in data analysis, according to the ICH-GCP, is to
submit a recap of the trial and its outcomes to the Sponsor and its Ethics
Committee, while the Indian GCP mentions that the investigator or the
institution should analyse the data, make a study report, and submit it to the
Sponsor and Ethics Committee. This tends to double the workload of the busy
investigators and Ethics Committee. In addition, this will result in various
study reports for various sites of a similar study.
The
Indian version added fresh headings to the Informed Consent Section of the
ICH-GCP, pertaining to biological samples like genetic material. The Indian GCP
offers patients the freedom to choose not to make the samples collected for
analysis available for possible future use; considering that there is a
possibility that the samples can be shared at any time. This section may create
a conflict in the Informed Consent Process and might discourage patients from
enrolling in clinical trials.
According
to the ICH-GCP, the monitor is the one who is responsible for verifying how
legible the documents are which are provided by the investigator or the site.
It does not mention that it would be mandatory to verify the informed consent
processes’ revisions. The Indian GCP states that the monitor should inform the
Sponsor and Ethics Committee of any deviations from and violations of the
protocol, including the ICF (informed consent form). This may be impossible
since the monitor does not have direct contact with the Ethics Committee.
Lastly,
after all the considerations are reviewed, it can be stated that the creation
of the Indian GCP came to happen so that the good deeds will be anticipated,
but it will be more applicable if the implications are made easy to comply
with.
Summary:
1. The
Indian GCP may have some guidelines that are hard to comply with compared to the
ICH-GCP.
2. In the
Indian GCP, both investigator and sponsors should sign the SOPs. ICH-GCP
expects the investigator to comply with SOPs and leave the monitoring of SOPs
to the auditors and monitors.
3. In
Indian GCP, the retained body samples (genetic material) may not be reused for
future trials when there is a need to repeat it.
4. ICH-GCP
states that the monitor should be the one to verify the legibility of
documents, while Indian GCP states that the monitor also needs to inform the
Sponsor and Ethics Committee for any violations from the protocol.
1. Related to ICH process
ICH allows any one designated by the investigator to conduct the consent process and to sign the consent form.
Indian GCP recommends that the investigator should sign the form. As per to FDA Inspection Informed consent obtained by individuals who lack the medical training, knowledge of the clinical protocol, or familiarity of the investigational product needed to be able to discuss the risks and benefits of a clinical trial with prospective subjects.
2. Powers of IEC
According to Indian GCP (2.4.2.6), the IEC has power to order discontinuation of a trial if the IEC finds that the goals of the trial have already been achieved mid-way or unequivocal results obtained.
As per ICH-GCP, this is the responsibility of independent data-monitoring committee (IDMC). The sponsor may consider establishing an IDMC to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend the sponsor whether to continue, modify, or stop a trial. This is possible, as the sponsor has to provide regular feedback and interim analysis of trial data on efficacy and safety to IDMC. For most global trials, the sponsor establishes an IDMC in a western country.
3. Investigator and sponsor’s SOPs
ICH allows any one designated by the investigator to conduct the consent process and to sign the consent form.
Indian GCP recommends that the investigator should sign the form. As per to FDA Inspection Informed consent obtained by individuals who lack the medical training, knowledge of the clinical protocol, or familiarity of the investigational product needed to be able to discuss the risks and benefits of a clinical trial with prospective subjects.
2. Powers of IEC
According to Indian GCP (2.4.2.6), the IEC has power to order discontinuation of a trial if the IEC finds that the goals of the trial have already been achieved mid-way or unequivocal results obtained.
As per ICH-GCP, this is the responsibility of independent data-monitoring committee (IDMC). The sponsor may consider establishing an IDMC to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend the sponsor whether to continue, modify, or stop a trial. This is possible, as the sponsor has to provide regular feedback and interim analysis of trial data on efficacy and safety to IDMC. For most global trials, the sponsor establishes an IDMC in a western country.
3. Investigator and sponsor’s SOPs
The Indian guideline (3.1.3) mandates that the sponsor and the
investigator should sign a copy of the Standard Operating Procedures (SOPs).
Besides, the investigator and his staff have to be aware and comply with SOPs.
This provision is practically impossible, as the sponsor will have to obtain signatures of all investigators in a trial on its large number of SOPs. Imagine the task of making multiple copies of hundreds of SOPs, delivering them to investigators, and obtaining their signatures! Besides, SOPs also get revised periodically and the whole cycle have to be repeated.
ICH-GCP expects the investigator to comply with the protocol and leaves the task of monitoring compliance to SOPs to monitors and auditors.
4 Investigator qualifications
The Indian GCP (3.3.1) insists that the investigator should be qualified as per the requirement of the Medical Council of India (MCI). This means that non-medical scientists e.g. pharmacists who organise the bio-equivalence studies, cannot become investigators. Even in the medical field, several eminent investigators have medical degrees from UK or US, which are not prescribed by MCI.
The qualifications of some of the senior investigators were not recognised as the medical institutions from where these investigators studied were not approved by MCI at that time. Implementation of this provision will require the monitors and auditors to ask the investigators for proof that their qualifications are in line with MCI. This provision can become a major hurdle for sponsors in selecting investigators and needs to be modified in line with ICH-GCP.
5 Investigators responsibility for data analysis
As per ICH-GCP, when the trial is completed, the investigator has to provide the Independent Ethics Committee (IEC) with a summary of the outcome of trial.
In contrast, Indian GCP demands that the investigator should sign and forward the data like Case Report Forms (CRF), results and interpretations, analyses and reports of the study from his/her centre to the sponsor and the ethics committee.
Usually data analysis is the function of the sponsor. However, this provision makes it a responsibility of the investigator, increasing his burden. The CRFs are never sent to IEC unless the IEC asks for them for some specific purpose e.g. suspected fraud. The IECs of major institutes, which are involved in several international trials, are already struggling to cope with large number of bulky documents submitted for their approval. This provision will increase IECs’ troubles, as they will have to create space for bulky CRFs and the clinical trial reports
6 Essential items for informed consent
Besides the essential items for informed consent listed in ICH-GCP, Indian guidelines (2.4.3.2) also cover issues of biological samples.
The consent has to include:
Right to prevent use of his/her biological sample (DNA, cell-line, etc) at any time during the conduct of the research
Foreseeable extent of information on possible current and future uses of the biological material and of the data to be generated from the research and if the material is likely to be used for secondary purposes or would be shared with others, clear mention of the same
Risk of discovery of biologically sensitive information
These items will make the consent form more complex to explain to the subject and may discourage him from participating in the research.
7 Monitor’s responsibilities
Monitor is supposed to inform the sponsor and IEC in case any unwarranted deviation from protocol or any transgression from principles of GCP. The monitor is not in contact with IEC and hence this requirement cannot be fulfilled. Monitor is also responsible for ensuring that CRFs are legible. As per ICH-GCP monitor has to verify that the documents provided by the investigator are legible. There is a glaring omission in the functions of the monitor. It does not include verification of informed consent.
8 Drug label
In the section on protocol (2.3.1.6), it is mentioned that drug label should include name and contact numbers of investigator and name ofinstitution. This is not a global practice. This will lead to practical difficulties in global trials where the labels are uniform with minor changes made if required by local laws and practice.
9 Document retention
Indian GCP (3.1.5) mandates that the sponsor should make arrangements for safe and secure custody of all study related documents and material for a period of three years after the completion of the study or submission of the data to the regulatory authority (ies) whichever is later. If the company does not get marketing approval within 3 years of completion of trial and if there is a need for regulator inspection after marketing approval, the records will not be available. It is desirable, as in the case of ICH-GCP, to link the records to marketing approval.
This provision is practically impossible, as the sponsor will have to obtain signatures of all investigators in a trial on its large number of SOPs. Imagine the task of making multiple copies of hundreds of SOPs, delivering them to investigators, and obtaining their signatures! Besides, SOPs also get revised periodically and the whole cycle have to be repeated.
ICH-GCP expects the investigator to comply with the protocol and leaves the task of monitoring compliance to SOPs to monitors and auditors.
4 Investigator qualifications
The Indian GCP (3.3.1) insists that the investigator should be qualified as per the requirement of the Medical Council of India (MCI). This means that non-medical scientists e.g. pharmacists who organise the bio-equivalence studies, cannot become investigators. Even in the medical field, several eminent investigators have medical degrees from UK or US, which are not prescribed by MCI.
The qualifications of some of the senior investigators were not recognised as the medical institutions from where these investigators studied were not approved by MCI at that time. Implementation of this provision will require the monitors and auditors to ask the investigators for proof that their qualifications are in line with MCI. This provision can become a major hurdle for sponsors in selecting investigators and needs to be modified in line with ICH-GCP.
5 Investigators responsibility for data analysis
As per ICH-GCP, when the trial is completed, the investigator has to provide the Independent Ethics Committee (IEC) with a summary of the outcome of trial.
In contrast, Indian GCP demands that the investigator should sign and forward the data like Case Report Forms (CRF), results and interpretations, analyses and reports of the study from his/her centre to the sponsor and the ethics committee.
Usually data analysis is the function of the sponsor. However, this provision makes it a responsibility of the investigator, increasing his burden. The CRFs are never sent to IEC unless the IEC asks for them for some specific purpose e.g. suspected fraud. The IECs of major institutes, which are involved in several international trials, are already struggling to cope with large number of bulky documents submitted for their approval. This provision will increase IECs’ troubles, as they will have to create space for bulky CRFs and the clinical trial reports
6 Essential items for informed consent
Besides the essential items for informed consent listed in ICH-GCP, Indian guidelines (2.4.3.2) also cover issues of biological samples.
The consent has to include:
Right to prevent use of his/her biological sample (DNA, cell-line, etc) at any time during the conduct of the research
Foreseeable extent of information on possible current and future uses of the biological material and of the data to be generated from the research and if the material is likely to be used for secondary purposes or would be shared with others, clear mention of the same
Risk of discovery of biologically sensitive information
These items will make the consent form more complex to explain to the subject and may discourage him from participating in the research.
7 Monitor’s responsibilities
Monitor is supposed to inform the sponsor and IEC in case any unwarranted deviation from protocol or any transgression from principles of GCP. The monitor is not in contact with IEC and hence this requirement cannot be fulfilled. Monitor is also responsible for ensuring that CRFs are legible. As per ICH-GCP monitor has to verify that the documents provided by the investigator are legible. There is a glaring omission in the functions of the monitor. It does not include verification of informed consent.
8 Drug label
In the section on protocol (2.3.1.6), it is mentioned that drug label should include name and contact numbers of investigator and name ofinstitution. This is not a global practice. This will lead to practical difficulties in global trials where the labels are uniform with minor changes made if required by local laws and practice.
9 Document retention
Indian GCP (3.1.5) mandates that the sponsor should make arrangements for safe and secure custody of all study related documents and material for a period of three years after the completion of the study or submission of the data to the regulatory authority (ies) whichever is later. If the company does not get marketing approval within 3 years of completion of trial and if there is a need for regulator inspection after marketing approval, the records will not be available. It is desirable, as in the case of ICH-GCP, to link the records to marketing approval.
As Indian GCP are indirectly became the law it needs to be in line
with the ICH GCP. Following are the some concerns with the recommendations need
to follow to remain in line with the ICH GCP.
Investigator qualifications:-
According to the section 3.3.1 of Indian GCP, investigator must be qualified as per the requirement of the Medical council of India. So pharmacists cannot become investigator for the BA/BE studies. Even knowledgeable investigators having medical degree of the foreign university are not approved by Medical council of India.
This guideline is major issue for selection of the Investigators by the sponsor and need to be change as per the ICH GCP.
Investigator and Sponsor’s SOP;-
According to the section 3.1.3 of Indian GCP it is mandatory for the sponsor and the investigator should sign a copy of the SOPs.
Practically, it is impossible for sponsor to obtain the signature in each copy of the SOPs. There are many SOPs and many of them revised periodically which led to obtaining signature again. Whereas ICH GCP are mainly expecting that investigator to comply with the SOPs.
ICH GCP expecting investigator should provide the summary of the outcome of the trial to the IEC. Whereas Indian GCP needs that the investigators should sign and forward data like CRF, results, analysis and report it to the sponsor.
Authority of ethical committee.
As per section 2.4.2.6 of Indian GCP the EC has authority to stop the a trial if ethical committee finds that the objective of the trial have been obtain midway or unrelated results have been obtained.
According to ICH GCP it is the duty of the Independent data-monitoring committee.
Essential wording of the Informed consent:-
In the Informed consent document following wording are necessary as per Indian GCP;
• Subjects have right to retain his/her biological sample at any time of trial.
• Risk of discovery of biologically sensitive information.
These wording is making difficult to obtain consent which may discourage the subjects from participating in trial.
Compensation;-
The Indian GCP mentions that when a subject is withdrawn from research for medical reason then he/she should get full compensation. This is true for healthy subject involve in BE study but for the cancer and HIV subjects in long clinical study then this may results into much costlier trial.
Monitor’s responsibility:-
According to Indian GCP, it is the responsibility of the Monitor to inform sponsor and Ethical committee for protocol violation which is practically impossible because monitor is not in contact with ethical committee.
As India going to be hub for Clinical research there is severe needs to update the guideline and should be incorporate country specific guideline to ICH-GCP guideline.
Conclusion/Recommendation
As discussed in background I would like to conclude that “Good clinical practice is the gold standard for clinical research industry.” But there are several needs to update the ICH-GCP. Following are the some recommendation which needs to be implemented.
Provide one set of GCP guideline for all trial i.e. for all class of medical device. There is severe need to give standard for phase IV trial and also needs to give importance to the same.
There are severe misleading issues in the ICH-GCP which sometimes became the hurdle in the process of patient’s recruitment. Give more specific guideline for inform consent process and mention the issues that are included in the informed consent especially for trials on cancer patients.
There are severe needs to improve the terminology used in the ICH-GCP. Because clinical trial not only involves the medical persons but it involve the professional from different educational background.
As regulatory authority are not in regular touch with the industry and there is very less communication between the reg. authority and industry. This communication gap should be filled and any issues related to product development need to be resolve.
Documentation is essential part of trail as per ICH GCP which did not give an assurance that trial is reliable and valid. Documentation part also needs improvement by systematic inspection of audit trail and by two-way comparison between original documents and CRF.
To ensure that ICH GCP has been followed in clinical trial, inspection by the regulatory authority is necessary. Following are the some recommendation for GCP inspection by authority.
Normally, a trial site has less than 2% chance of getting inspection by the authority. Even CRO and IEC have very less chance of being inspected. So, more number of inspections is needed.
Regulatory authorities have very few trained inspectors for ensuring compliance with the ICH GCP. So, there is severe need to ensure that inspectors get trained on ICH-GCP. As way to ensuring compliance is only inspection as per GCP. Training can also increase the efficiency for inspection.
It is suggested that GCP should not be implemented on the researcher when research is not conducted for economical purpose but conducted for knowledge purpose. So many valuable thoughts can come out which otherwise remain hidden under the pressure of the cost for implementation of ICH GCP.
As ICH-GCP is very informative but it is not having reference mention in it so it needs to revises. It should be necessary to have delegate from academia and health care professional into the revision of ICH-GCP. So it needs to update like other guidelines.
Finally, I conclude that “All trials should be done well but good clinical practice might not the only method to make sure that trial was conducted by good ways” but “Many researchers are not following the acceptable standards so in such cases it should be mandatory to follow the ICH GCP, and have better ways to ensure conduct of trial is right or wrong.”
According to Indian GCP, it is the responsibility of the Monitor to inform sponsor and Ethical committee for protocol violation which is practically impossible because monitor is not in contact with ethical committee.
As India going to be hub for Clinical research there is severe needs to update the guideline and should be incorporate country specific guideline to ICH-GCP guideline.
Conclusion/Recommendation
As discussed in background I would like to conclude that “Good clinical practice is the gold standard for clinical research industry.” But there are several needs to update the ICH-GCP. Following are the some recommendation which needs to be implemented.
Provide one set of GCP guideline for all trial i.e. for all class of medical device. There is severe need to give standard for phase IV trial and also needs to give importance to the same.
There are severe misleading issues in the ICH-GCP which sometimes became the hurdle in the process of patient’s recruitment. Give more specific guideline for inform consent process and mention the issues that are included in the informed consent especially for trials on cancer patients.
There are severe needs to improve the terminology used in the ICH-GCP. Because clinical trial not only involves the medical persons but it involve the professional from different educational background.
As regulatory authority are not in regular touch with the industry and there is very less communication between the reg. authority and industry. This communication gap should be filled and any issues related to product development need to be resolve.
Documentation is essential part of trail as per ICH GCP which did not give an assurance that trial is reliable and valid. Documentation part also needs improvement by systematic inspection of audit trail and by two-way comparison between original documents and CRF.
To ensure that ICH GCP has been followed in clinical trial, inspection by the regulatory authority is necessary. Following are the some recommendation for GCP inspection by authority.
Normally, a trial site has less than 2% chance of getting inspection by the authority. Even CRO and IEC have very less chance of being inspected. So, more number of inspections is needed.
Regulatory authorities have very few trained inspectors for ensuring compliance with the ICH GCP. So, there is severe need to ensure that inspectors get trained on ICH-GCP. As way to ensuring compliance is only inspection as per GCP. Training can also increase the efficiency for inspection.
It is suggested that GCP should not be implemented on the researcher when research is not conducted for economical purpose but conducted for knowledge purpose. So many valuable thoughts can come out which otherwise remain hidden under the pressure of the cost for implementation of ICH GCP.
As ICH-GCP is very informative but it is not having reference mention in it so it needs to revises. It should be necessary to have delegate from academia and health care professional into the revision of ICH-GCP. So it needs to update like other guidelines.
Finally, I conclude that “All trials should be done well but good clinical practice might not the only method to make sure that trial was conducted by good ways” but “Many researchers are not following the acceptable standards so in such cases it should be mandatory to follow the ICH GCP, and have better ways to ensure conduct of trial is right or wrong.”
In general, Indian GCP
guidelines are in line with ICH-GCP. However, there are significant differences
in some of the areas, which will make the task of compliance difficult for the
sponsors, investigators and ethics committees.
Investigator qualifications
The Indian GCP (3.3.1) insists
that the investigator should be qualified as per the requirement of the Medical
Council of India (MCI). This means that non-medical scientists e.g. pharmacists
who organise the bio-equivalence studies, cannot become investigators. Even in
the medical field, several eminent investigators have medical degrees from UK
or US, which are not prescribed by MCI.
The qualifications of some of
the senior investigators were not recognised as the medical institutions from
where these investigators studied were not approved by MCI at that time.
Implementation of this provision will require the monitors and auditors to ask
the investigators for proof that their qualifications are in line with MCI.
This provision can become a major hurdle for sponsors in selecting
investigators and needs to be modified in line with ICH-GCP.
Investigator and sponsor’s
SOPs
The Indian guideline (3.1.3)
mandates that the sponsor and the investigator should sign a copy of the
Standard Operating Procedures (SOPs). Besides, the investigator and his staff
have to be aware and comply with SOPs.
This provision is practically
impossible, as the sponsor will have to obtain signatures of all investigators
in a trial on its large number of SOPs. Imagine the task of making multiple
copies of hundreds of SOPs, delivering them to investigators, and obtaining
their signatures! Besides, SOPs also get revised periodically and the whole
cycle have to be repeated.
ICH-GCP expects the
investigator to comply with the protocol and leaves the task of monitoring
compliance to SOPs to monitors and auditors.
Investigators responsibility
for data analysis
As per ICH-GCP, when the trial
is completed, the investigator has to provide the Independent Ethics Committee
(IEC) with a summary of the outcome of trial.
In contrast, Indian GCP
demands that the investigator should sign and forward the data like Case Report
Forms (CRF), results and interpretations, analyses and reports of the study
from his/her centre to the sponsor and the ethics committee.
Usually data analysis is the
function of the sponsor. However, this provision makes it a responsibility of
the investigator, increasing his burden. The CRFs are never sent to IEC unless
the IEC asks for them for some specific purpose e.g. suspected fraud. The IECs
of major institutes, which are involved in several international trials, are
already struggling to cope with large number of bulky documents submitted for
their approval. This provision will increase IECs’ troubles, as they will have
to create space for bulky CRFs and the clinical trial reports.
Powers of IEC
According to Indian GCP
(2.4.2.6), the IEC has power to order discontinuation of a trial if the IEC
finds that the goals of the trial have already been achieved mid-way or
unequivocal results obtained.
As per ICH-GCP, this is the
responsibility of independent data-monitoring committee (IDMC). The sponsor may
consider establishing an IDMC to assess the progress of a clinical trial,
including the safety data and the critical efficacy endpoints at intervals, and
to recommend the sponsor whether to continue, modify, or stop a trial. This is
possible, as the sponsor has to provide regular feedback and interim analysis
of trial data on efficacy and safety to IDMC. For most global trials, the
sponsor establishes an IDMC in a western country.
As Indian centres are part of
global trials, they are reviewed by IDMC. This means that Indian IECs at
different sites will not be involved in this process and cannot fulfill this
requirement of Indian GCP. IDMC is also recommended in Indian GCP (3.1.5).
Hence, these two provisions are likely to create a conflict of responsibilities
between IEC and IDMC!
This provision also could
become a nightmare for regulatory authorities, as there is scope for misuse of
this provision by sponsors of local Schedule Y open registration trial.
The goal of these local trials
is to confirm whether the Indian safety and efficacy results are in line with
the international clinical trial data. If a sponsor finds that the results are
comparable to international data in initial 25-30 patients, he can submit this
data to IEC to request them to stop the trial and later present the IEC
recommendation to the regulatory authorities for obtaining registration.
Essential documents for IEC
In the appendix V, essential
documents for IEC files are listed. This means the sponsor and the investigator
have to provide additional copies of most documents to IEC and also ensure that
they are filed. It will be difficult for the monitor and the auditor to check
compliance to this provision, as the sponsor does not have direct access to IEC
documents.
Essential items for informed
consent
Besides the essential items
for informed consent listed in ICH-GCP, Indian guidelines (2.4.3.2) also cover
issues of biological samples.
The consent has to include:
Right to prevent use of
his/her biological sample (DNA, cell-line, etc) at any time during the conduct
of the research.
Foreseeable extent of
information on possible current and future uses of the biological material and
of the data to be generated from the research and if the material is likely to
be used for secondary purposes or would be shared with others, clear mention of
the same
Risk of discovery of biologically sensitive information.
Risk of discovery of biologically sensitive information.
These items will make the consent form more complex to explain to the subject and may discourage him from participating in the research.
Compensation
In the essential items for
consent, there are also mandatory clauses on compensation, which are as
follows:
Free treatment for research
related injury by the investigator/ institution
Compensation of subjects for disability or death resulting from such injury In addition, there is a whole section on compensation related issues (2.4.5 and 2.4.7).
Indian GCP mandates that when a subject is withdrawn from research for medical reasons related to the study, the subject should get the benefit for full participation.
Compensation of subjects for disability or death resulting from such injury In addition, there is a whole section on compensation related issues (2.4.5 and 2.4.7).
Indian GCP mandates that when a subject is withdrawn from research for medical reasons related to the study, the subject should get the benefit for full participation.
While this provision seems
appropriate for studies in healthy volunteers e.g. bio-equivalence study, it
could lead to issues in a clinical trial of a chronic disease in patients. A
cancer patient taking part in a long trial of a new product is assured of
regular follow up and costly investigations. If he is withdrawn because of a
medical reason e.g. adverse event, he receives free medical treatment for the
event but does not receive any other benefit.
However, such a patient can
cite this provision and insist on regular follow up and free investigations
assured for the trial for the whole duration of trial!
The other provisions for
compensation are prescriptive:
The sponsor (company,
government, institution) should agree to provide compensation for any serious
physical or mental injury or to provide insurance coverage
Research subjects who suffer physical injury in a trial are entitled to financial/other assistance to compensate them equitably for any temporary or permanent impairment or disability subject to confirmation from IEC.
Research subjects who suffer physical injury in a trial are entitled to financial/other assistance to compensate them equitably for any temporary or permanent impairment or disability subject to confirmation from IEC.
In cases of death, their
dependents are entitled to material compensation These provisions, probably,
are an attempt to protect Indian patients, who are often illiterate and from
lower socio economic class. Monitor’s Qualifications Indian GCP guidelines
(3.2) suggest that the monitor should have adequate medical, pharmaceutical
and/or scientific experience. As most monitors are pharmacists or science
graduates, they would not have adequate medical experience and hence will not
qualify as monitors!
Monitor’s responsibilities
Monitor is supposed to inform
the sponsor and IEC in case any unwarranted deviation from protocol or any
transgression from principles of GCP. The monitor is not in contact with IEC
and hence this requirement cannot be fulfilled. Monitor is also responsible for
ensuring that CRFs are legible. As per ICH-GCP monitor has to verify that the
documents provided by the investigator are legible. There is a glaring omission
in the functions of the monitor. It does not include verification of informed
consent.
Drug label
In the section on protocol
(2.3.1.6), it is mentioned that drug label should include name and contact
numbers of investigator and name of institution. This is not a global practice.
This will lead to practical difficulties in global trials where the labels are
uniform with minor changes made if required by local laws and practice.
Document retention
Indian GCP (3.1.5) mandates
that the sponsor should make arrangements for safe and secure custody of all
study related documents and material for a period of three years after the
completion of the study or submission of the data to the regulatory authority
(ies) whichever is later. If the company does not get marketing approval within
3 years of completion of trial and if there is a need for regulator inspection
after marketing approval, the records will not be available. It is desirable,
as in the case of ICH-GCP, to link the records to marketing approval.
Recommendations
Time has to come to review
some of the provisions of Indian GCP guidelines, as they are soon to become a
law. Some of the sections related to the investigator, IEC, monitor, drug label
and documentation have to be viewed pragmatically from compliance and practical
considerations. Some others - informed consent and compensation — need
discussion on global practices vis-…-vis Indian socioeconomic realities.
Overall, there is an urgent need for another harmonisation between Indian GCP
and ICH-GCP!
Difference Between Indian GCP & ICH-GCP
1.
In Informed Consent
Process, As per ICH - GCP any one designated by the investigator to conduct and
to sign the consent form. (Section 4.8.8) but in Indian GCP Investigator should
sign the form. (Section 2.4.3.1).
2.
In IEC section, Indian GCP
recommended the maximum no. of IEC member (12-15) but ICH-GCP Maximum number is
not detailed. In IEC section, Indian GCP recommended that Member Secretary
belongs to the same Institution but ICH- GCP Not recommended.
3.
As per Indian GCP Monitor
is also responsible for ensuring that CRFs are legible. where ICH-GCP state
that Monitor has to verify that the documents provided by the investigator are
legible.
4.
As per Indian GCP, Study
related documents/materials should be safe guarded by the sponsor for 3 years.
(Section 3.1.5) but in ICH-GCP the records are linked to marketing approval.
5.
Investigator qualifications:
The Indian GCP investigator should be qualified as per the requirement of the
Medical Council of India (MCI).
6.
Investigator and sponsor’s
Sops: The Indian guideline mandates that the sponsor and the investigator
should sign a copy of the Standard Operating Procedures (SOPs). Besides, the
investigator and his staff have to be aware and comply with SOPs; ICH-GCP
expects the investigator to comply with the protocol.
7.
Investigators
responsibility for data analysis: As per ICH-GCP, when the trial is completed,
the investigator has to provide the Independent Ethics Committee (IEC) with a
summary of the outcome of trial. In contrast, Indian GCP demands that the
investigator should sign and forward the data like Case Report Forms (CRF),
results and interpretations, analyses and reports of the study from his/her
centre to the sponsor and the ethics committee.
8.
Powers of IEC: According to
Indian GCP (2.4.2.6), the IEC has power to order discontinuation of a trial if
the IEC finds that the goals of the trial have already been achieved mid-way or
unequivocal results obtained. As per ICH-GCP, this is the responsibility of
independent data-monitoring committee (IDMC).
9.
EC Quorum: ICH GCP min of 5
members and Indian GCP min of 7 members.
10.
EC Members: Indian GCP
gender representation at least 1 women
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