Ethics Committees in India have come a long way

Around 2004 when I asked a friend from Pfizer Outcomes Research the hassles of conducting phase trials in India, top on his concern list was the weak ethical review climate that prevailed in India then. His company would bring in more trials to India if they felt confident that Indian Institutional Ethics Committees (IECs) and their review of project proposals would comply with international norms. As per our own admission on the FERCAP website (http://www.fercap-sidcer.org/home.asp), the Indian regulators were not confident of our Ethics committees in 2006. The web page on India has a posting that had confessed about the situation prevailing then:

“Transparency and accountability in (Indian Medical) research currently depends on individual institution which may have allegiance to different groups, and may be in need for benefits from Sponsors. (Indian) IECs are used to closed door meetings and generally communications from IECs focus on final decisions without specifying reasons or information on how to improve the research study to the researchers”

But that was 2006. In mid-2009, while the Medical Research Ethics Committees in India are still an evolving breed, they have clearly moved in the right direction since then. Two developments are worth noting. One, the Indian Council of Medical Research (ICMR) and the Indian chapter of FERCAP have made a move towards registration and accreditation of IECs. We also expect some oversight by the Indian regulator DCGI. Second, India’s clinical trial registry (www.ctri.in) is now operational and compliant with the WHO Trial Registration 20-item Data Sets (http://www.who.int/ictrp/network/ctri/en/index1.html) and other norms (http://www.who.int/ictrp/network/ctri/en/index.html)

FERCI

The Forum for Ethical Review Committee in India (FERCI) was formed in Dec 2002 as the Indian chapter of FERCAP. It was not very active for a few years after formation but has recently been rejuvenated and one of its recent initiatives is IEC accreditations in India (personal communication with ex-Deputy Director ICMR Dr. Nandini Kumar). Two leading Indian research sites - King Edward Memorial (KEM) Hospital and Tata Memorial Hospital, both in Mumbai - have invited audit teams and have been accredited under the SIDCER/FERCAP program. The audits went smoothly with only a few discrepancies and the Tata Memorial online approval process was also found to be acceptable. I see that many other IECs are to follow in this program. FERCI objectives include:

• Establish & foster communication between IECs in India
• Act as a national collaborating agency for ethics reviews
• Organize & facilitate meetings, trainings & symposia on ethical review processes
• Assist in the development & implementation of SOPs for ethical review based on WHO guidelines
• Co-ordinate national communications & issues with other global bodies

CTRI

The Indian Clinical Trial Registry is available / encouraged for all clinical research except Bioavailability and Observational trials. Registration is free and presently can be done for on-going studies also. CTRI registration requires some parameters beyond the WHO recommendation that may be essential from an Indian perspective. For example, name of the IECs/ Institutional Review Boards (IRBs) that have approved the study/sites and DCGI approval status are required. Later, CTRI may even insist on approvals from accredited IECs. Conversely, not all IECs in India currently insist on the WHO data set and CTRI registration while reviewing study proposals.

ICMR guidelines for IECs have existed since long and are by and large adopted as Standard Operating Procedures (SOPs) by most IECs in India including for-profit and non-profit IRBs. While Indian IECs have come a long way since the 2004 observation of my American friend, they still need to invest in further training of members and institute transparent functioning in order to avoid a Coast IRB situation in India.

Jayesh Chaudhary

CEO

VEDIC LIFESCIENCES P LTD

jayesh.chaudhary@vediclifesciences.com

Ethical concern and associated with Oncology Clinical Trial

Cancer is arguably the most fatal disease. It is estimated that one third of drugs under discovery or development are for Oncology, but still cancer is almost incurable. Many Cancer Drugs are themselves carcinogenic or toxic. So unlike other therapeutic area’s, it is unethical and unsafe to include healthy volunteers for non-therapeutic oncology clinical trials. That is the reason why non-therapeutic clinical trials are being conducted on patients who are already suffering from this disease, but I am not sure if it is ethical to keep even cancer patients on sub-therapeutic dosage.

There are lots of developments which are taking place around the globe to reduce the timeline and number of patients, which eventually reduce the risk & pain involved during non-therapeutic oncology clinical trial. One such development is Phase 0 clinical trials, which is developed in response to the United States Food and Drug Administration’s (FDA) recent exploratory Investigational New Drug (IND) guidance, to expedite the clinical evaluation of new molecular entities. It involves lesser number of patients for shorter duration and also promises to shorten the duration of non-therapeutic trial by three to six months, i.e. the timeline for taking anticancer drugs from the laboratory to the clinic. Unlike Phase I clinical trials which are designed to establish the MTD, the Phase 0 clinical trial’s maximum dose can be that at which a PK/PD response is observed or target modulation is measured, providing that no drug-associated toxicity is found. Although it does not give any Patient benefit but it gives a flexibility to conduct Phase 1 Clinical trials at much higher dose and with less patient population.

Another significant development which took place is modified study design. The designs which are more or less in use are Accelerated Titration Designs and simulation study designs. Current phase I trials often take a long time to complete and provide little information about inter-patient variability or cumulative toxicity. These designs are developed to get the necessary information by reducing the number of patients and duration in non-therapeutic Oncology clinical trials (http://linus.nci.nih.gov/~brb/AcceleratedTitration.pdf).

Still these developments will not eliminate the suffering a patient volunteer may endure in non-therapeutic trials. Although these study designs promise that the duration of risk will be less or the number of patient volunteers involved in such studies will be less, it can not be eliminated. The main problem in drug discovery & development of oncology drug is unavailability of laboratory methods which can accurately predict which entity will be effective against a particular class of human cancer.

The patients who are suffering from such a painful disease get involved in clinical trials for a variety of reasons, which I believe is unethical. However, the conduct of non-therapeutic Oncology clinical trials is necessary for the advancement of healthcare in society. Hence I believe that the conduct of non-therapeutic clinical trials is a necessary sin, which Pharma companies & CRO have to indulge in for the benefit of society.

Dhirendra V. Singh,

Business Development Manager,

Vedic Lifesciences Pvt Ltd

bizdev@vediclifesciences.com

Oncology Clinical Trial: Long Timeline and Breakthrough

Millions of dollars are spent on creating new treatment methods for cancer. The main reason for high cost of cancer treatment method is long time, complication and cost involved in Drug Discovery and Development process. Considering the timeline and cost involved in Clinical Trial, we developed a model. This model is based a disease surveillance on cancer and studying the trends of Cancer studies. This model is developed to reduce the timeline without compromising quality and by reducing the cost.

The major area’s which we have covered in this model are Long & Unethical early stages, failure at early stages, Study design related problem like end point & study criterion, General acceptance of report and Reasons for long time line like low recruitment rate, IND complications, multiple effects, low survival rate of patients etc.

V – Onco© model has been developed to identify exact input, process and output parameters, in order to bring an effective mechanism in place. Most important aspect of any mechanism is inputs. One cannot expect perfect results without accurate inputs. According to this model, the inputs have to be provided by CRO and Sponsor. Before looking for a CRO the sponsor should have definite plan to introduce modern models for conducting trial like Phase 0, New Phase I designs for reducing the timeline and getting early indication of investigational products. Considering the complications involved in study the sponsor should ease the inclusion exclusion criterion. While selecting a CRO the sponsor must consider the knowledge base, their patent & investigators database, regulatory environment and ability to absorb the SOP.

Once selected, CRO has to play role of partner and select a site not only with high disease prevalence, experienced investigator & favorable regulatory environment but also with clinical research supportive environment. If they are lacking in some area, they help the CRO as a guide or knowledge partner and help the sponsor in selection of right partners with high patient base and knowledge base with current industry patterns. CRO can provide their best inputs through accurate and innovative research methodologies (like translational research), site selection and site feasibility.

With accurate inputs, process becomes easier with boundaries of well defined SOPs and well trained monitor. It is the responsibility of CRO to empathize with the site personnel and patient volunteers for fulfilling their needs related to clinical study. There should be a system of patient follow-up by creating validating and updating the database. There should also be a system of IP administration if patient is unable to visit. Site effectiveness should be highest in order to conduct qualitative trials with 100% source data verification.

CRO support is most crucial aspect of this process which includes complete site based support and recruitment of ICH – GCP trained physicians.

Creating awareness and marketing of suitable clinical trial is also part of the process. All these process parameters are focused on faster subject recruitment with quality data, favorable regulatory environment & understanding of clinical trials among physicians and patients. This can not be done overnight rather a continuous effort is required to achieve this goal. CRO has to conduct a disease prevalence study to know the extent of disease spread. CRO should also maintain database of Primary health centers & general physicians and create awareness about Clinical research to get their support for Volunteer recruitment, which is very vital for Cancer Studies.

Last stage of this system is a suitable output which is directly dependent on above two steps. As per V – Onco© model, with precise inputs and efficient process, one tends to get desired output in terms of faster regulatory approval, quality data, shorter timelines and better return on investment.

As industry demands quality data in most cost effective manner, we have designed V – Onco© model. Industry trends and patterns have changed due to economic slowdown which suggests cost effective research and CRO can be best partner to achieve the same.Below is model for reducing the timeline of Oncology Clinical Trials:


V – Onco© Model:







Business Development Manager

Above V – Onco^© is copyrighted and property of Vedic Lifesciences Pvt Ltd. It shall not be used without written consent of Vedic Lifesciences Pvt Ltd.