Author: Shabbir Chunawalla

The DCGI is planning to shift the process of approving clinical trial applications online. Each trial will be assigned a unique identity number. Pharma companies, ethics committees, doctors/investigators responsible for trials would regularly update information on the online database. It is expected to put the details of the patients, severe side effects they may suffer and compensation paid to them. A regulator may seek additional details.

The details about the indications for the drug, the disease it seeks to cure will have to be uploaded.

The details of the investigator or doctor conducting the trial, the details of his team, the site of the trial and whether such trials are being conducted in other parts of the world will be given.

The details of the targeted patients group will be given. It is to be informed whether any vulnerable groups such as children,pregnant women, nursing mothers are participating in the trial.

There should be a disclosure regarding the composition of the ethics committee, their meetings and proceedings.

There is a huge amount of packaging waste. Several groups are working on creating wrappers and containers that are edible, soluble and with flavour. You can drink coffee from a cup and then eat the cup itself. A cocoa packet can be put into hot water and its casing dissolves. Edible packaging is inspired by nature  — see how we munch through apples and grapes which are encased in protective layers.

David Edwards, Harvard, has created WikiCells  — a skin that combines small particles of dried fruit, chocolate shavings or other edibles. It is held together by electrostatic force. Monsolo, an Indiana-based company, is making a similar film using polymers. Loliware, NY-based firm has moulded edible biodegradable cups from natural pectins and cane juice, and they are infused with flavour. Eventually, all packaging should be eligible.

A clinical trial is a series of test treatments that are necessary to perform before a drug or chemical can be allowed to enter the market.

The clinical trial has three phases. They are conducted by the principal investigators ( PI ) and sponsored either by a pharmaceutical company or through an academic institution or private group of individuals.

Phase I

A drug is administrated to a small group ( 20-80 ) of healthy individuals to assess its safety. This is done after the substance is tested on animals to examine how humans react to it.

Phase II

Her the group is somewhat larger — 100 to 300 patients. They are given a drug to test its efficacy and examine how it is treating the ailment for which it is intended.

Phase III

It consists of giving the drug to a much larger group of patients ( 1000 — 3000 ) to verify its safety and therapeutic effectiveness and compere these to the result from existing treatments.

Data from patients’ blood tests and other exams is regularly collected  in all phases to corroborate findings.

Contract Research Organisations ( CROs )

Pharmaceutical companies often farm out trials to clinical research organisations, also known as contract research organisations ( CROs ) . The CRO first conducts a feasibility survey of potential doctors who might participate and then determine which ones, how many will be involved, as well as the number of test subjects.

Approval applications are made to the regularly bodies —

• the Drug Controller General of India ( DCGI )
• the Central Drugs Standard Control Organisation ( CDSCO )
• ethics committees of all hospitals involved in the trial.

After getting approval for the trial, all personnel involved are trained in protocols.

The patients are informed of potential risks and their consent is obtained before commencing the procedure.

The Drug and Cosmetics Act , 1945 has been amended to reflect rules that define new drug and clinical trial and outlines the necessary steps to obtain permission to import and manufacture new drugs and fixed dose combination in India.

A drug that has not been developed in India (developed in a foreign country ) cannot be tested on humans for the first time in India. It means Phase I trial needs to be conducted in the country of its origin. Then only permission is given for trial in India. Thus largely only Phase II and Phase III studies are conducted in India. This safeguard is to prevent Indians from becoming guinea pigs.

Compensation of Participants

These rules were framed by the Ministry of Health and Family Welfare on 30th Jan.2013 and were notified in the Gazette. In case of injury to the clinical trial subject, he/she shall be given free medical management as long as required. If the injury is due to the clinical trial itself, the subject is eligible for additional financial compensation. The issue in the industry is who pays and how much.The rules say clinical trial sponsors are liable to pay medical expenses for a subject even if he/she is injured in an accident or a mishap that had nothing to do with the trial itself.

In the West, there is insurance for most trials where the patient files a claim. In case of India, regulators expect sponsors to  ‘procactively’ provide compensation.

Placebo Treatment

Administrating a placebo to show the effectiveness of the actual drug has come under scrutiny. It is considered unethical, and sponsors are compelled to compensate the placebo group for any untoward events.

Serious Adverse Events ( SAEs )

These comprise injuries or adverse reactions that trial subjects experience. They are supposed to be reported to the DGCI within 24 hours of its occurrence. Here the possibility of the subject not informing the PI of the adverse event or his taking treatment at another doctor/hospital has not been taken into account.

Size of the Clinical Research Industry

It is estimated to be $ 250-300 million.

Manpower Employed

It employs up to 15000 people.

Ranjit Roy Choudhury Committee, 2013 Recommondations

• All principal investigators (PI ), hospitals, institutes, ethics, committees associated with clinical trials must receive accreditation.
• Do away with the New Drug Approval Committees ( NDACs ). These 12 committees function under DCGI. Replace these by a single Technical Review Committee.
• Audio-visual recording of every subject’s informed consent.
• Sponsor’s liability to compensation restricted to SAEs that are related to the use of drug or placebo or the drug’s therapeutic inefficiency.

OAI, NAI, VAI

FDA conducts inspections and verifies study data. There may be OAI or Official Action Initiated or NAI — No Action Initiated or VAI — Voluntary  Action Initiated.

ACRO

It is the Association of Contract Research Organisations of India.

Good Clinical Research Practices ( GCPs )

There are formulated so as to make CROs conform to GCPs.

Clinical Trials

India’s share of global trials is only 5-10 per cent, but the share is going up. After China, India is the most preferred destination for clinical trials thanks to its native patient pool, faster enrollment and low cost. The US and Euorpean companies are outsourcing their work to India to curtail their R&D costs. It saves them 30-50 per cent in costs.

The outsourced components are :

• big data management of clinical trials.
• stability studies
• toxicity slide preparation and evaluation.

Manpower Required in Clinical Trials

• Trained medical/dental investigators and co-investigators in charge of administrating new formulations.
• pharmacology, pharmacy, life sciences and biotech graduates to facilitate the studies by managing the clinical sites.
• clinical trial co-ordinators ( CTC ) for procuring patients.
• Clinical research associates ( CRA ) who are essentially data and site monitors.
• clinical data managers.