Need for ethical oversight of clinical trials in india

You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Cressey, D. India shakes up rules on clinical trials. Nature Download citation. Published : 21 August Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

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Per Notice13Mar20 , when the application is solely to conduct a clinical trial, the DCGI also requires the sponsor to submit the international non-proprietary name INN or generic name, drug category, dosage form and data supporting IP stability in the intended container-closure system for the duration of the clinical trial see the CTRules Second Schedule, Table 1 for detailed data requirements.

If approved, the DCGI will grant permission for a period of three 3 years to both manufacturers of new drugs or investigational new drugs and manufacturers of unapproved APIs. In exceptional circumstances, the DCGI may extend the period of permission for an additional year.

Once approved, the import license must remain valid for three 3 years from the date of its issue, unless suspended or cancelled. In exceptional circumstances, the DCGI may extend the license for an additional year.

See also IND for a checklist of manufacturing and import related forms to be included in a global clinical trial application submission. According to the CTRules , the sponsor must submit a fee of 5, Indian National Rupees INRs per product with an application for permission to manufacture or import the IP to be used in a clinical trial.

As explained in IND , the DCGI does not require a drug import license to be obtained when an ethics committee EC has granted approval for the conduct of an academic clinical trial that will be using a permitted drug formulation with a new indication, a new route of administration, a new dose, or a new dosage form. A copy of the EC approval for the trial must be provided to the Port office at the time of import along with a letter of undertaking that specifies the quantity of the drug being imported and states that it will be used exclusively for the academic clinical trial.

As per the CTRules , for new drugs already approved outside India, the results of local clinical trials may not be necessary to submit along with the application to import or manufacture a new drug if the DCGI decides to grant permission on the basis of data available from countries to be specified in a future DCGI order.

See Regulatory Authority topic, Scope of Assessment subtopic for detailed waiver requirements. This decision will vary depending on the specific clinical trial phase proposed and the clinical parameters related to the study drug. The CTRules requires the IB to contain the version number, release date, and the following sections:. Refer to the CTRules for detailed content guidelines. See the Investigational Products topic, Product Management subtopic for additional information on IP supply, storage, and handling requirements.

Additionally, per Notice13Mar20 , when the application is solely to conduct a clinical trial, the DCGI also requires the sponsor to submit the international non-proprietary name INN or generic name, drug category, dosage form and data supporting IP stability in the intended container-closure system for the duration of the clinical trial see the CTRules Second Schedule, Table 1 for detailed data requirements.

As noted in the CTRules the applicant is required to provide the following:. In addition, the CTRules and IND explain that the DCGI will consider a local clinical trial waiver for approval of a new drug already approved in other countries if the following conditions are met:.

Per the CTRules and IND , the labeling of any new drug or investigational new drug manufactured or imported for the purpose of conducting a clinical trial or for testing and analysis should include the following items:.

According to the CTRules and IND , in the event that a new drug or investigational new drug manufactured for clinical trial or testing and analysis purposes is left over, remains unused, incurs damage, has an expired shelf life date, or has been found to be of sub-standard quality, the drug must be destroyed and the action taken should be recorded. The CTRules also describes investigational product IP management requirements in the context of proposed protocol contents to be submitted as part of the clinical trial application submission.

Note: The regulatory sources provide overlapping and unique elements so each of the items listed above will not necessarily be in each source. The G-XBiolMat definition also includes the following:. As per the G-XBiolMat , these biological specimens or human material samples may be obtained from the following sources:.

In the case of international research collaboration involving human biological material transfer, the G-XBiolMat and the G-ICMR indicate that the export of all biological materials is to be covered under existing GOI and ethics guidelines. The exchange of human biological material from and to WHO Collaborating Centres for specific purposes, as well as for individual cases of diagnosis or therapeutic purposes, may not require permission.

However, Indian participating center s must have appropriate regulatory approval and registration to receive foreign funds for research. For more information, see the HumBiol-ImprtExprt.

In addition, per the G-ICMR , it is necessary for all health research involving human participants and their biological material and data to be reviewed and approved by an appropriately constituted ethics committee EC.

In addition to the informed consent form ICF required elements listed in the Informed Consent topic , the G-ICMR require investigator s to communicate the following information to participants in the ICF regarding the use of their biological samples:. The GCLP further indicates that prior to specimen collection, appropriate counseling should be completed and written consent obtained. Human Genetic Research Consent Requirements.

As stated in the G-ICMR , investigator s must comply with stringent norms and exercise caution in conducting the consent process with participants for genetic research purposes.

The following considerations must be taken into account during this process:. However, even if group consent is taken, it will not be a replacement for individual consent.

In addition, as indicated in the G-ICMR , the transfer of human biological material to be stored at a biorepository or a biobank, or another institution, must be communicated to the participant.

Please refer to Section 11 of the G-ICMR for detailed consent requirements associated with storing human biological materials in a biorepository or a biobank. See the Informed Consent topic, Required Elements and Participant Rights subtopics for additional information on informed consent. Details on the most recent India updates are available here. We would welcome your feedback on ClinRegs.

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China DRC Guinea. India Kenya Liberia. Malawi Mali Mexico. Peru Sierra Leone South Africa. Tanzania Thailand Uganda. United Kingdom United States Vietnam. Regulatory Authority. Scope of Assessment. Regulatory Fees. Ethics Committee. Scope of Review. Ethics Committee Fees.

Authorizing Body. Clinical Trial Lifecycle. Submission Process. Submission Content. Timeline of Review. Trial Initiation. Safety Reporting. Progress Reporting.

Definition of Sponsor. Trial Authorization. Informed Consent. Documentation Requirements. Required Elements. Compensation Disclosure. Participant Rights. Vulnerable Populations. Mentally Impaired. Investigational Products. Definition of Investigational Product.

Product Management. Definition of Specimen. Consent for Specimen. Additional Resources. View recent profile updates View all sources. Preface, 5. Regulatory System. About Us. Preface, 4. Clinical Trial of New drugs. Overview As delineated in the CTRules and IND , India has a decentralized process for the ethical review of clinical trial applications, and requires ethics committee EC approval for each trial site.

Sections Ethics Committees ECs. Role in Biomedical and Health Research Approval Process As discussed in Notice15Sept19 and chapter IV of the CTRules , any institution or organization that intends to conduct biomedical and health research is required to have an EC to review and oversee the conduct of such research before the study is initiated and throughout its duration. Multicenter Research As delineated in the G-ICMR , in a multicenter research study, all of the participating study sites are required to obtain approval from their respective ECs.

Introduction and Sections , and 6. Overview As indicated in the G-ICMR , the ethics committee EC may charge a reasonable fee to cover the expenses related to optimal functioning to conduct reviews. The suspended or cancelled EC can appeal to the DCGI within the period specified in the show cause notice, and, after consideration, the DCGI may respond by taking one or more of the following actions: Withdraw the notice Issue a warning to the EC describing the deficiency or defect observed during an inspection Reject the results of the clinical trial Suspend for a specified period or cancel the registration, or Debar its members to oversee any future trial for a specified period The aggrieved EC may file an appeal to the Government of India Central Government within 60 working days.

The suspended or cancelled EC can appeal to the DHR, and, after consideration, the DHR may respond by taking one 1 or more of the following actions: Issue a warning to the EC describing the deficiency or defect observed, which may adversely affect the rights or well-being of the study participants; Suspend the EC for a specified period or cancel the registration, or Debar its members from overseeing any future biomedical health research for a specified period The aggrieved EC may file an appeal to the Government of India Central Government within 45 working days.

Clinical Trial Application Language Requirements While there is no specified language requirement in the regulatory requirements for documents submitted to CDSCO, since the SUGAM portal is in English, it is reasonable to conclude that clinical trial application submissions should be in English as well.

EC Requirements Each institutional EC has its own application form and clearance requirements, which can differ significantly regarding the number of copies to be supplied and application format requirements. Preface, 3, 5. Ethics Committee Confirmation of Review and Approval While the CTRules require ethics committee review and approval before a clinical trial can commence, there are no stated requirements related to the investigator providing confirmation to the sponsor.

Chapter 8. The Philosophy of Evidence-Based Medicine. London: Wiley-Blackwell; Teira D, Reiss J. Goodman SN. Toward evidence-based medical statistics. Ann Intern Med. Sackett DL, et al. New York: Churchill Livingstone; Berg JW, et al. New York: Oxford University Press; Informed consent: is it a myth? Emanuel EJ, et al. Oxford: Oxford University Press; Miller F, Brody H. A critique of clinical equipoise: therapeutic misconception in the ethics of clinical trials.

Hastings Cent Rep. Wendler D, Miller F. Deception in the pursuit of science. Arch Intern Med. Deng C, et al. Challenges of clinical trial design when there is lack of clinical equipoise: use of a response conditional crossover design. J Neurol. Temple R, Ellenberg SS.

Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 1: ethical and scientific issues. Anderson JA. The ethics and science of placebo-controlled trials: assay sensitivity and the Duhem—Quine thesis.

J Med Philos. Howick J. Hellman S, Hellman DS. Of mice but not men: problems of the randomized clinical trial. N Engl J Med. Freedman B. Equipoise and the ethics of clinical research. Edwards SJ, et al. Ethical issues in the design and conduct of randomised controlled trials. Health Technol Assess. Sackett D. Lilford RJ. Ethics of clinical trials from a Bayesian and decision-analitic perspective: whose equipoise is it anyway?

Ethics and practice: alternative designs for phase III randomized clinical trials. Control Clin Trials. Glantz LH, et al. Shapiro H, Meslin E. Ethical issues in the design and conduct of clinical trials in developing countries. Riis P. Thirty years of bioethics: the Helsinki Declaration — New Rev Bioeth. Miller FG, Wertheimer A. Facing up to paternalism in research ethics. Kummar S, et al. Nat Rev Cancer. Giordano S.

The Declaration of Helsinki: some reflections. J Med Ethics. McCulloch P, et al. Randomised trials in surgery: problems and possible solutions. Lee C, Morton CC. Structural genomic variation and personalized medicine. Longo Dan L. Tumor heterogeneity and personalized medicine. Fleck LM. A recent regulatory change with respect to IISs is that academicians who carry out trials with 'new drugs' no longer need approval from the DCGI for the conduct of the trial and IEC approval would suffice. This is provided that these studies are not intended for generating data to make a regulatory submission.

In the event that the IEC feels that there could be a potential overlap between the academic and regulatory purposes of the trial, they should notify the office of the DCGI. If the IEC does not hear from the DCGI within 30 days, it should be presumed that no permission is needed from the licensing authority.

Institutional Ethics Committees function according to standard operating procedures [SOPS] that are usually available on their websites. Projects submitted essentially undergo two broad types of review- Full board or full committee review [for all projects that present more than minimal risk] or expedited review [for projects that pose no more than minimal risk; e.

The CTRI[ 16 , 17 ] is a free, online portal that allows both investigator-initiated and regulatory studies to be registered. It is recommended that all studies are registered at a public portal. Registration is important from a publication standpoint point as editors of many Biomedical Journals will not accept papers that have interventional studies not registered with a Clinical Trials Registry.

Investigators must ensure that written, informed consent is obtained from all participants in a clinical trial. For trials that involve vulnerable participants children or mentally challenged patients for example and involve a new chemical entity or a new molecular entity, the investigators in addition have to ensure audio visual recording of the informed consent process gazette notification dated 19 th November, An SAE is defined as an untoward medical occurrence during a clinical trial that is associated with death, in patient hospitalisation if the study was done on outpatient basis , prolongation of hospitalisation if the study was conducted on in-patient basis , persistent or significant disability or incapacity, a congenital anomaly or birth defect or is otherwise life-threatening.

In addition, send to Chairman of IEC and the Head of the institution where the trial has been conducted within 14 calendar days of occurrence of the event. Compensation in a clinical trial is needed both when death occurs or when there is clinical trial-related injury. The formulae for compensation for both are described below. Compensation for birth defect or congenital anomaly: Medical care to be provided as long as required and a lumpsum amount to be kept in a fixed deposit that would bring in a monthly interest equal to half of the minimum wage of an unskilled worker in Delhi.

For institutes that do not have them, this would be a good committee to constitute. Since clinical trial related injury or death is equally possible both with pharmaceutical industry and investigator-initiated academic studies, budgetary provisions need to be in place at the institutional level for the medical management of adverse events [AEs], SAEs and provision of insurance to trial participants.

Understand that the regulator can inspect the site at any time and that he can cancel the trial permission and discontinue the study. Therefore preparedness of the study site at all times must be ensured. Per this notification, medical devices are broadly classified as investigational medical devices and registered or approved medical devices. Chapter VII of this notification states that clinical trials with the former need both IEC and DCGI approval, while academic studies [studies not intended for manufacturing or marketing the device] with the latter, need only IEC approval.

Table 2 covers must know and good to know aspects of clinical trial research. Several governmental and non-governmental organisations within the country fund academic research and the academician needs to make an application to them with application formats and timelines being available on their home pages.

In addition, several pharmaceutical companies in the country also fund investigator initiated research. The funding from the industry could be by way of provision of drug supplies or monetary support or both. The control of the study including its conception, conduct and analysis remains exclusively with the investigator in these studies and would need a clear memorandum of understanding with the industry funder.

Studies that involve a collaborator from outside India need an additional approval from the Health Ministry Screening Committee, a committee that works out of ICMR and meets quarterly to assess these projects for collaborative merit.

The academic investigator needs to be up to speed in reading, understanding and applying regulations and work in tandem with the pharmaceutical industry for greater patient benefit. The ECs now have a larger than ever onus need to appreciate and understand risk — benefit and to empower themselves through repeated training and use of standard operating procedures given that it is known that the quality of IEC review across the country remains variable.