The Hindu : Health / Policy & Issues : Worried court asks Centre to file details on clinical trials

The Hindu : Health / Policy & Issues : Worried court asks Centre to file details on clinical trials.

 

Source : THE HINDU, Oct 8, 2012

Business Line : Opinion : Why clinical trials evoke suspicion

Business Line : Opinion : Why clinical trials evoke suspicion.

Source : THE HINDU Business Line – Sep 5, 2012

Harvard University’s online free course on ‘Clinical & Public Health Research’

Ex-DCGI asks medical community to pursue Harvard University’s online free course on ‘Clinical & Public Health Research’

September 04, 2012, 0800 IST  – Source : Pharmabiz News

Anticipating big scope for opportunities for clinical trials in India in the coming years, former Drug Controller General of India (DCGI) Dr Surinder Singh has suggested to the medical community to pursue the Harvard University’s online free course on ‘Clinical and Public Health Research’. He has made the request through an online discussion forum of doctors and health professionals, and forwarded a letter, sent to him by the vice-president of Piramal Enterprises, Dr Swati Piramal who was recently elected to the Harvard Board of Overseers, a 350-year old governing board of the Harvard University in Boston in USA. By persuading the medical community to pursue the course, Dr Singh opines that the Indian pharmaceutical industry has the potential to become ‘Pharmacy of the World” in another one decade. He declares that there is big scope for clinical trials in the near future in India, so the course will help the medical professionals in a big way. His email to the forum members says that recently there has been a paradigm shift in the Indian pharma industry’s thrust from production of generics to innovation, i.e. drug discovery & development which entails an increase in conduct of clinical trials, especially the ones which require high degree of domain expertise i.e. micro-dosing studies (phase 0), phase I & phase II clinical trials. “Having been the former Drug Controller General of India till November 2011, I can appreciate the importance of this course for the medical fraternity and bring it to your notice, so that you may like to avail this opportunity to enhance your skills to become top professionals in clinical research or investigator for conduct of clinical trials,” he said in his email to the members. According to him drugs from India are exported to more than 200 countries and vaccines to about 150 countries across the world. Currently Dr Surinder Singh is the director–in-charge at the National Institute of Biologicals, Noida. Dr Swati Piramal’s letter to Dr Singh clarifies that the course, “Quantitative Methods in Clinical and Public Health Research’ is the online adaptation of material from the Harvard School of Public Health’s classes in epidemiology and biostatics. This course will address the need by covering the principles of biostatics and epidemiology used for public health and clinical research.

DCGI issues detailed check-list to ensure quality of informed consent by trial subjects

DCGI issues detailed check-list to ensure quality of informed consent by trial subjects

August 22, 2012, 0800 IST – Source : Pharmabiz News

With a view to further streamline the ‘informed consent’ aspect in the clinical trials, the Drugs Controller General of India (DCGI) has issued detailed format and exhaustive check-lists to ensure the quality of informed consent being taken from the trial subjects.

For the first time, the Central Drugs Standard Control Organization (CDSCO) has prescribed the “essential elements” of informed consent documents used for enrolling subjects to a drug trial. The sponsors were asked to ensure that all subjects, before signing up for the trials, are given detailed information based on these essential elements.

“In all trials, a freely given, informed, written consent is required to be obtained from each study subject. The investigator must provide information about the study verbally as well as using patient information sheet, in a language that is non-technical and understandable by the study subject. The subject’s consent must be obtained in writing using an informed consent form. Both the patient information sheet as well as the informed consent form should have been approved by the ethics committee and furnished to the Licensing Authority. Any changes in the informed consent documents should be approved by the ethics committee and submitted to the licensing authority before changes are implemented,” said the notice by the DCGI.

The essential elements are designed to ensure that subjects are aware of their rights (e.g. for compensation etc.) and clearly understand that they are agreeing to participate in a research of their free will even though alternate treatment options may be available.

Specifically, the CDCSO has outlined 14 essential elements that will have to be incorporated into informed consent documents. These include: a statement that the study involves research and explanation of the purpose of the research; expected duration of the subject’s participation; a description of the procedures to be followed, including all invasive procedures; a description of any reasonably foreseeable risks or discomforts to the subject; a description of any benefits to the subject (if no benefits are expected, the subjected should be made aware of this); information on appropriate alternative procedures or therapies available to the subject; a statement describing the extent to which confidentiality about the subject’s records would be maintained; information on the trial’s treatment schedule and the possibility of random assignment of each treatment (in case of randomised trials); information on compensation and/or treatments available to the subject in the event of a trial-related injury; information on whom to contact for trial-related queries and rights of a subject, especially in case of a trial-related injury; information on the payment, if any, to the subject for participating in the trial; and a statement that participation is voluntary and that the subject can withdraw at any time while clarifying that withdrawal from the trial will not involve any penalty or less of benefits to which the subject is otherwise entitled.

In addition, the CDSCO put six additional elements that may be required for informed consent documents depending on the trial. These include, among other things, a statement that the subject will be notified if significant new findings are highlighted during the course of the research which may affect the subject’s willingness to continue participating in the study.

 

CDSCO notifies draft rules on inspection of clinical trial sites

CDSCO notifies draft rules on inspection of clinical trial sites
August 09, 2012, 0800 IST – Source Pharmabiz News

In a move to further streamline the clinical trials in the country, the Central Drugs Standard Control Organisation (CDSCO) has finalized and issued draft rules regarding the inspection of premises of clinical trial sites by the regulatory officials with or without prior notice.

“The premises of sponsor/clinical research organization and clinical trials shall be open to inspection by the officer of the CDSCO, who may be accompanied by an officer of the concerned state drug control authority to verify compliance to the requirements of Schedule Y, good clinical practices and other applicable regulation,” according to the notification seeking to change the Drugs and Cosmetics Act (D&C Act).

“The sponsor/CRO, investigators shall allow CDSCO officer who may be accompanied by an officer of the concerned State Drug Control Authority to enter, with or without prior notice, any premises of sponsor/CRO and clinical trial site to inspect, search, seize any record, data, document, books, investigational drugs etc. related to clinical trials and provide adequate replies to any queries raised by the inspecting authority in relation to the conduct of the trial,” the document said.

The rules, already approved by the DTAB, will be the third amendment to the Drugs and Cosmetics Rules, 2012 and will be implemented after final notification, the notification said, while seeking inputs and suggestions from the stakeholders.

The rules, to be incorporated in Part X-A after Rule 122 DAB, in detail lays down mandatory procedures for getting permissions, approval of the ethics committee, registration with Clinical Trials Registry-India, reporting of injuries and death, and procedures for submitting replies if notices were issued by the CDSCO on the lapses.

If any company fails to comply with any of the conditions, the licensing authority, may after giving an opportunity, will take proceed to take actions, as required. The can be warning letter on the deficiency found during the inspection, recommendation for rejecting the study, suspension or cancellation of the trial permission and restriction of the investigator/CRO from conducting studies, the draft rules said.

CDSCO issues draft guidelines to calculate compensation for victims of clinical trials

CDSCO issues draft guidelines to calculate compensation for victims of clinical trials

August 07, 2012, 0800 IST – Source : Pharmabiz News

The Central Drugs Standard Control Organisation (CDSCO) has issued draft guidelines for determining the quantum of financial compensation to be paid in case of clinical trial related injury or death, as part of streamlining the entire sector.

“Presently there is no specific provision under Drugs and Cosmetics Rules for payment of compensation in case of clinical trial related injury or death of the subject. However, the Good Clinical Practice (GCP) Guidelines for Clinical Trials of India under para 2.4.7 provides that the research subject who suffers physical injury as a result of their participation in clinical trials are entitled to financial or other assistance to compensate them equitably for any temporary or permanent impairment or disability subject to confirmation from Ethics Committee. In case of death, their dependents are entitled to material compensation. Guidelines further provide that it is the obligation of the sponsor to pay the compensation. The concerns were also raised in Parliament and other forums regarding payment of compensation in the cases of injury or death in clinical trial,’’ said the guidelines issued for inviting feedbacks from the stakeholders.

“There needs to be a simple and expeditious procedure for payment of compensation and criteria for determining the amount of financial / material compensation to be paid in the cases of study related injury to the subject or in case of death to his/her nominee(s). To incorporate specific provisions for procedures to be followed for payment of compensation in case of trial related injury or death, draft rules have already been published which is under consideration for finalization. The proposed draft rule 122 DAB in clause (1) and (2) provides that in case of trial related injury or death financial compensation will be provided in accordance with the recommendations of the Ethics Committee as per the guidelines prescribed for the purpose. By the time the amended rules come into force, the guidelines should be in place for the purpose of implementation of the rules,’’ it said.

This guidance document describes the methods to be followed by the Ethics Committees for calculating the quantum of financial compensation to be paid in case of clinical trial related injury or death. These guidelines apply to all such cases of clinical trial including BA/BE studies related injuries or death occurring during clinical trial of drugs including biological and medical devices covered under Drugs & Cosmetics Act.

The guidelines also have made specific methods to calculate the quantum of financial compensation, based on parameters like the age and income of the deceased, seriousness of the injury, and the percentage of the permanent disability.

Registration of Ethics Committees becomes mandatory for clinical trials

Registration of Ethics Committees becomes mandatory for clinical trials

August 07, 2012, 0800 IST – Source : Pharmabiz.com

Registration of Ethics Committees attached with the Clinical Trial Organisations (CROs) for conducting clinical trials has been made mandatory in the country by the Drugs Controller General of India (DCGI).

A draft notification, issued by the Central Drugs Standard Control Organisation (CDSCO), said, “No ethics committee shall review and accord its approval to a clinical trial protocol without prior registration of the committee with the licensing authority as defined in clause (b) of rule 21”.

Earlier in October last year, the Drugs Technical Advisory Board (DTAB), the highest decision-making body under the Union health ministry on technical matters, had taken the decision to make registration of Ethics Committees mandatory in the country for clinical trials. The DTAB’s decision came in the wake of widespread complaints that the Ethics Committees at most of the clinical trial sites are not independent and also not active with no monitoring of the trials by the authorities.

So far, only the registration of clinical trials with the drugs controller general of India (DCGI) is mandatory in the country. Independent ethics committees are constituted by the individual companies and its registration is not mandatory. For starting any clinical trial, the approval of the ethics committee is crucial as without which the DCGI will not provide his sanction for beginning the study in the country.

As per the notification, an application for registration of ethics committee shall be made to the licensing authority in accordance with the requirements prescribed in Schedule Y-I. The licensing authority after being satisfied that the requirements of the rules have been complied with and the conditions of the registration will be observed, may grant registration subject to the condition stated therein.

The ethics committee will review and accord its approval to a clinical trial as per Schedule Y, the Good Clinical Practice Guidelines for Clinical Trials in India and other applicable regulatory requirements for safeguarding rights, safety and well being of the trial subjects.

The ethics committee shall allow inspectors/officials of CDSCO to enter the premises of the committee to inspect any record, data, document etc. related to clinical trial and provide adequate replies to any queries raised by the inspecting authority in relation to the conduct of clinical trial. The registration, unless it is sooner suspended or cancelled, shall be valid for a period of five years from the date of issue.

If the licensing authority is not satisfied, he shall reject the application and shall inform the applicant of the reasons for such rejection and the conditions which must be satisfied before the registration can be granted. If the ethics committee fails to comply with any of the conditions of registration, the licensing authority may after giving an opportunity to show cause why such an order should not be passed, by an order in writing stating the reasons therefore, suspended or cancel the registration of the ethics committee for such period considered necessary.

The ethics committee whose registration has been suspended or cancelled by the licensing authority may within ninety days of the receipt of the copy of the order by him prefer an appeal to the central Government and the central Government may, after giving an opportunity of being heard, confirm, reverse or modify such order, the draft notification said.

State drug control officials not empowered to monitor clinical trials

State drug control officials not empowered to monitor clinical trials: Dr Jagashetty

June 12, 2012, 0800 IST – Source : Pharmabiz News

State drugs control departments have no powers to keep tabs on the clinical trials conducted in their states unless they are empowered as per the Drugs & Cosmetics Act & Rules, according to Dr BR Jagashetty, drugs controller, government of Karnataka.

The department’s team of inspectors has no authority to enter the premises of the clinical trial organizations, said Dr Jagashetty following the recent statement by the Drugs Controller General of India (DCGI), Dr G N Singh who said that the state DCs were required to keep a close vigil on the illegal human studies.

Without empowerment under the D&C Act & Rules, there is no question of inspection and even the clinical trial companies will not permit the inspectorate teams to enter the premises for the inspection, he added.

Further state drugs control departments have no information on clinical trial or clinical research organizations. There is also no mention of human studies in the D&C Act. So far no state drugs control departments have been involved in conducting inspections on clinical trial companies.

A key focus of a clinical trial is to assess the safety of the drug and efficacy. There has been several initiatives to look at pharmacovigilance, a adverse drug monitoring activity, from the government side. “There is definitely need for an audit and a dedicated team of inspectors to be in place to carry out the inspections of all clinical trials,” said Karnataka drugs regulator, said Dr Jagashetty.

India has around 40 clinical research organizations (CROs) including domestic and multinational companies. Out of these, there are around 20 leading companies and Karnataka is home to at least 15 of these CROs. The notable names are Ecron Acunova, Clinigene which is part of Biocon Limited, Lotus Labs. Omnicare, Vaatsalya, Treista Life Sciences which is part of Health Care Global Enterprises (HCG), St. John’s Medical College Clinical Trial Centre, Synchron, D2L, SMO India and Infinitus which are the homegrown companies.

In addition the state also has a presence of global majors include Quintiles, PharmaNet, PharmaOlam and ClinTech International to name a few. Besides this, there are corporate and government hospitals engaged in clinical trials. These cover Manipal Hospital, Fortis, Columbia Asia, Ramaiah Memorial Hospital where international pharma majors identify a principal clinical investigator to carry out the human studies.

Health ministry’s efforts to make registration of BA/BE studies mandatory with CTRI stuck in red-tapism

Health ministry’s efforts to make registration of BA/BE studies mandatory with CTRI stuck in red-tapism
February 06, 2012, 0800 IST – Source : PharmaBizNews

The union health ministry’s efforts to make the registration of bioavailability and bioequivalance (BA/BE) studies mandatory with the Clinical Trial Registry of India (CTRI) are stuck in the bureaucratic red-tapism as different departments of the ministry are passing the buck on funding the project.

According to sources in the the National Institute of Medical Statistics (NIMS), which has been given the responsibility to make the necessary changes in its web network to incorporate the BA/BE features, the NIMS could not take up the project so far as no funding has come from the ministry.

Though the then Drugs Controller General of India (DCGI) Dr Surinder Singh had asked the NIMS to get the funding for the project from Indian Council of Medical Research (ICMR), the ICMR is yet to the provide any funding to NIMS for the project. “We are waiting for funds. The moment we get the funding, we will start the project,” a senior official said.

Earlier, after more than two years since the registration of clinical trials was made mandatory in the country, the health ministry had taken the decision in-principle to make the registration of BA/BE studies mandatory, on the same lines of the other clinical trials in the country. The then DCGI Dr Surinder Singh had directed the senior officials in the CTRI to make the necessary changes in its web network to incorporate the BA/BE features.

According to sources, the ministry wanted to streamline the BA/BE studies in the country. So far, registration of BA/BE studies with the CTRI was optional. Once it is made mandatory, all the BA/BE studies have to be registered with the CRTI without which the DCGI will not give permission to conduct BA/BE studies which are conducted on healthy volunteers.

Hundreds of BA/BE studies are going on at any given time in the country at different clinical research centres. BA/BE studies which take about three months time, are conducted for finding the bioavailability and bioequivalance of a drug, especially the generic drugs and the combination drugs which are already in the market. For getting the license for a new combination drug or generic drug, it is mandatory to submit the BA/BE study results to the DCGI office.

 

Health ministry tightens norms on clinical trials, action on two violations

January 25, 2012, 0800 IST – Source : PharmaBizNews

The Union health ministry has tightened the norms on clinical trials after amending necessary rules regarding obtaining informed consent from the trial subjects and extending financial assistance to the victims, and has found two cases of violations in trials in the recent past.

The two cases came to the notice of the Drug Controller General of India (DCGI) were about the trial of drug Tadalafil in a hospital at Indore and the trial of an anti-cancer drug by Axis Clinical Research, Hyderabad, prompting the authorities to take action, sources said.

The DCGI initiated action following report t in respect of allegedly flouting of clinical trial norms at Maharaja Yashwant Rao Hospital and Mahatma Gandhi Memorial College, Indore where the drug Tadalafil was used for clinical trial for Pulmonary Arterial Hypertension (PAH).

“The office of DCG(I) directed CDSCO (WZ) on 12-07-11 to carry out a investigation to ascertain the facts. Accordingly an investigation was carried out by the office of CDSCO(WZ) and State Drugs Controlling Authority on 10-08-11 in respect of clinical trials conducted at M G M Medical college and associated M Y Hospital in Indore. As per the investigation report, a trial was conducted by Dr Anil Bharani and Dr Ashish Patel with tadalafil in patients with group-1 pulmonary hypertension without permission from DCG(I),” sources said.

“The study with Tadalafil was initiated on 18-09-05 when the drug was not approved for the said indication in the country. However, the drug was approved in the country for another indication – male erectile dysfunction on 10.06.2003. In view of above, vide letter dated 02-11-11 directed both the doctors namely Dr Anil Bharani and Dr Ashish Patel to stop the clinical trial of Tadalafil in Pulmonary Arterial Hypertension and restricted them to conduct any clinical trial for a period of six months,” sources said.

Another case that attracted action from the authorities was the trial of an anti-cancer drug by Axis Clinical Research, on poor people without proper informed consent. The investigations revealed that the firm conducted bioequivalence study on an already approved anticancer drug and there were certain irregularities with respect to informed consent process, review and decision making process of Ethics Committee.

“The permission granted to the firm for conducting bioequivalence and bioavailability study was suspended on 22.06.2011. Consequent to this, the firm, on 04.07.2011, has submitted corrective actions being taken by them including revised Standard Operative Procedures (SOP’s) for subject recruitment process, informed consent process, review and decision making process of the Ethics Committee. Based on further investigations and verifications, Axis Clinical Research, Hyderabad was granted ‘NOC’ to conduct Bio-equivalence study  subject to fulfillment of various condition regarding Informed Consent Process including documentation of the Informed consent process through Audio-Video means, functioning of Ethics Committee and investigators,” sources said.

In order to strengthen the regulations relating to clinical trials, following proposals  for amendments in Drugs and Cosmetics Rules, 1945 have been  approved by Drug Technical Advisory Board (DTAB) and a draft notification was published some time back to incorporate effective provisions for providing financial compensation to the trial subjects in case of trial related injury or death.

Another step in this regard was enhancement of responsibilities of Ethics Committee, Sponsor & Investigator to ensure that financial compensation as well as medical care is provided to the trial subjects who suffer trial related injury or deaths. Amendment was also made on the format for obtaining informed consent of trial subjects to include the details of address, occupation, annual income of the subject so as to have information regarding socio-economic status of the trial subjects.