Introduction to Clinical Research

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Introduction to Clinical Research A clinical trial (also clinical research) is a research study in human volunteers to answer specific health questions. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people and ways to improve health. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings.

Why Participate in Clinical Trials •Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research
Who can participate in Clinical Trials •All clinical trials have guidelines about who can participate. Using inclusion/exclusion criteria is an important principle of medical research that helps to produce reliable results.
•The factors that allow someone to participate in a clinical trial are called "inclusion criteria" and those that disallow someone from participating are called "exclusion criteria".
•These criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions.
•Before joining a clinical trial, a participant must qualify for the study.
•Some research studies seek participants with illnesses or conditions to be studied in the clinical trial, while others need healthy participants.
•It is important to note that inclusion and exclusion criteria are not used to reject people personally.
• Instead, the criteria are used to identify appropriate participants and keep them safe.
•The criteria help ensure that researchers will be able to answer the questions they plan to study.

What are the Different types of Clinical Trials •Treatment trials test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
•Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vitamins, vaccines, minerals, or lifestyle changes.
• •Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.
• •Screening trials test the best way to detect certain diseases or health conditions. • •Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.
Different Phases of Clinical Trial Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions:
•In Phase I trials, researchers test a experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
•In Phase II trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
•In Phase III trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.
•In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
Clinical trials are conducted in phases. The trials at each phase have a different purpose and help scientists answer different questions
Risks of Participating in Clinical Trials There are risks to clinical trials:
•There may be unpleasant, serious or even life-threatening side effects to experimental treatment.
•The experimental treatment may not be effective for the participant.
•The protocol may require more of their time and attention than would a non-protocol treatment, including trips to the study site, more treatments, hospital stays or complex dosage requirements.
Protection of Safety of Participants •The ethical and legal codes that govern medical practice also apply to clinical trials.
•In addition, most clinical research is federally regulated with built in safeguards to protect the participants.
•The trial follows a carefully controlled protocol, a study plan which details what researchers will do in the study.
• As a clinical trial progresses, researchers report the results of the trial at scientific meetings, to medical journals, and to various government agencies.
• Individual participants' names will remain secret and will not be mentioned in these reports.

Structure and function of Drug Regulatory Authorities in India
1. Drugs and Cosmetics Act 1940 regulates the use of drugs in India. The act has been amended intermittently but still requires many changes as recommended by the expert group. Drugs and Cosmetics Rules 1945 are framed under the Act. The Pharmacy Act 1948 and Drugs & Magic Remedies (objectionable Advertisements) Act 1954 are other relevant regulations. The government has issued drug policies in 1986, 1994 and pharmaceutical policy in 2002. Schedule Y of Drugs and Cosmetic Rules, which regulates clinical trials in India has been amended in 2005. This gives the details of the documents required. A copy can be down loaded from internet.
2. The central government is responsible for laying standards, approval of new drugs, quality control of imported drugs and licensing of large volume injectables, vaccines, biotechnology products and operation of blood banks. So clinical trials can only be approved by central government. The state governments are responsible for licensing of manufacturers, distributors and sale outlets. It is also required to have surveillance on products through inspection and sample testing & take follow-up actions.
3. The Drug Controller General of India who works under ministry of health is responsible for the functions of Central Govt. State Drug Controllers exercise the functions of state governments. The regulatory functions of state and Centre suffer due to inadequacy of manpower, testing laboratories, and lengthy legal procedures. An excellent presentation on regulations for clinical trials in India by Dr Bhawana Sharma Consultant ICMR is available on the departmental computer and could be referred to.
Pharmacovigilance in India:
1. Pharmacovigilance principally involves the identification and evaluation of safety signals. Dr Ashwini Kumar DGCI in a recent presentation on pharmacovigilance in India said that the only gain at present is the knowledge how not to do it. Now fresh strategy has been formulated. The approach will be a collaborative and interactive effort of health care professionals reporting adverse drug reactions on forms available on the net. The organizational structure includes National Pharmacovigilance Centre in the office of DGCA (CDSCO) with two zonal centers. One located in AIIMS covers North and East and other located in GS Medical College Mumbai covering South and West. Each has two regional centers. One for North is at lady Harding Medical College and for East at NRS Medical College Kolkata. Regional Centre for South is at Madras Medical College Chennai and one for West is at KEM Hosp & MC Mumbai. I hope the pharmacovigilance in India makes a mark and generates excellent data for ADR.
Code of Federal Regulations (CFR):
Code of Federal Regulations is important trials for approval in USA. CFR are especially important on subjects on which ICH guidelines are not available. 21 CFR 11 is a classical example.
Learning the language of the ‘tools’ used Most of the submissions are on computers using e-forms. Familiarity with these tools is hence essential. This is especially true when data entry and data analysis is required. Regulations for e-submissions have also been formulated and need to be known. While computers and templates make the job easier it also breeds casualness. In the process of ‘cut & paste’ even old dates get copied. Security of information and authentication of e-documents is to be learnt and followed.
List of Forms to be used for permissions from DGCI (as per schedule Y) Application for Form No.
Permission to import or manufacture new drugs for sale or to undertake clinical trials Form 44
Import of drugs for the purpose of examination, test or analysis Form 12
Import license granted for drugs for examination, test or analysis Form 11
Grant of license to manufacture drugs for the purpose of examination, test or analysis Form 30
License granted to manufacture drugs for the purpose of examination, test or analysis Form 29
Information required in respective Appendices to be submitted for permissions from DGCI (as per schedule Y)
Application for Appendices
Permission to import or manufacture new drugs for sale/ undertake clinical trials (Form 44) I & IV & III
New Drug substances discovered in India/ abroad I
Permission to initiate specific phase of clinical trial X, V, VII, VIII
Submission of Clinical trial reports II
Ethics Committee Clearance VIII
Details of Adverse events /Serious AEs XI
Investigator Undertaking VII
Informed consent V
Studies in Special population I
What are the career prospects and scope of clinical research in india?
A fledgling industry till a while back, clinical research is now ready to take off in India. In fact, we are the second most preferred destination for outsourcing clinical trials for the global pharma industry today, which is 90 per cent cheaper than the West.
Global consultancy McKinsey & Co estimates that by 2010, global pharma majors would spend around $1-1.5 billion just for drug trials in the country. According to a Confederation of Indian Industry study, clinical trials in India in 2002 generated $70 million in revenues. It predicts that it would grow to $200 million by 2007 and anywhere between $500 million and $1 billion by 2010.
Almost all top names, including Novo Nordisk, Aventis, Novartis and GlaxoSmithKline, have started running clinical drug trials in India lately, while some, such as Eli Lilly and Pfizer, which started much earlier, conduct tests on a number of their new drugs. Besides, a variety of both India-based and global contract/clinical research organizations that specialize in outsourced clinical trials management are working to expand India's clinical-trials business.
These include Quintiles, Omnicare, PharmaNet and Pharm-Olam (all US-based). There are more than 50,000 jobs in clinical research in India.
Reason? India offers a large native patient base with a truly diverse gene pool on which broad-based clinical trials can be validated. Our climatic conditions also offer a perfect breeding ground for a range of different diseases. The only impediment preventing the industry from expanding is a severe shortage of clinical research associates and chemists familiar with complex chemical synthesis. Globally, more than 2.5 lakh positions are lying vacant.