PARR 2 Today we will be learning about:

What is Drug Development process? What is Clinical Research? How is Clinical Research relevant in a Drug Development

process? What are the careers involved in Clinical Research? The stability of Clinical Research Industry and rewards

involved.

I am sure you will appreciate the importance of numerous drugs and the role they play in our day-to-day life. All problems require a solution. In the health care-industry, problem means a “disease”, and this problem requires a solution in the form of a medicine. This medicine or drug is developed after a molecule goes through various stages under drug development process.

You being a Clinical Research aspirant, it adds value to know the drug development process and the role of clinical research process in drug development process.

Study the graphical representation of the drug development process:

Pharmaceutical companies produce medicines after an extensive research, which is carried out in various stages. The stages can be broadly termed as Drug Discovery, Pre-Clinical, and Clinical Research processes.

Drug Discovery Process:

In medicine, biotechnology or pharmacology, drug discovery is the process by which drugs are discovered and/or designed.

The process of Drug Development starts with having certainty on the field of medicine that the pharmaceutical company selects. For e.g. Dermatology.

After the selection of the field or area, the right lead compound or target identification from the library (earlier produced for future research by the researchers) is determined.

This results in the synthesis of this lead compound chemically.

Then the chemically synthesized molecules are tested for its potential effects using computers and 3D structure activity relationship.

Hereafter, the potential molecule (also known as Investigational product, or New Chemical Entity) that is determined will go to the pre-clinical testing (which is performed on animal).

Pre-Clinical process:

Pre-Clinical tests are the tests conducted on animals to establish safety and efficacy of the NCE in animals before the clinical testing (testing in humans) is initiated.

Pre-Clinical testing is conducted on various species of rodents and non-rodents.

Testing is carried out for different duration for extended studies on safety and efficacy.

Then toxicity, mutagenicity and carcinogenicity studies are carried out to check if there is any associated impairment with the long-term use of the NCE.

Once the effects are found to be safe and effective in animals, then the NCE is manufactured in small-scale in order to perform clinical trials. This is because the molecule should be used in human beings in a particular dosage form (like tablet, capsule, etc)

Clinical Research process:

What is Clinical Research? Clinical Research can be defined as trials that evaluate new drugs, biologicals, or medical devices on human beings in strictly, scientifically controlled settings, in order to establish the safety and efficacy of the experimental therapy.

After development of the dosage form, the Investigational New Drug (IND) is given as a tablet, capsule, etc for Clinical Research.

Clinical Research is an important part of drug development as all drugs that are discovered should be finally beneficial to human beings. Therefore, this is the stage where efficacy and safety of the molecule should be proved.

To start, the investigational product gets tested on 20-80 healthy human volunteers depending on the type of study, this stage is called Phase I.

Once the regulatory department approves the results from these tests, the investigational product gets into Phase II. The IND is tested on 100-400 patients in this stage.

Again after approval from the regulatory department on Phase II results, the investigational drug goes for Phase III testing, which involves 500-10,000 patients.

The IND is then launched into the market on approval from the regulatory board.

After the launch there is post marketing surveillance performed to ensure that there are no ill affects of the drug in the long run. This stage is called Phase IV.

Insight into Clinical Research:

Clinical Research is an evergreen field, which requires skilled/trained life science personnel. Thus it is here to stay in India.

Apart from the research on new drugs (allopathic) that are developed for the various diseases, the new burst in the ayurvedic, genetic, biotechnology and medical devices related research springs more opportunities. This new extension ensures greater stability both in clinical operations, clinical data management, medical writing and other fields within clinical research.

Apart from the benefits of these developments there is a great demand for the generic drugs that are being brought into the market from various companies.

So there are both innovator drugs and generic drugs that are undergoing various trials all around the world.

About 10%-15 % of the study population for all trials is Indians and due to the pool of patients and the right medical facility, the Indian contribution into clinical research is continuously increasing.

Careers in Clinical Research:

Here, we would go through the various positions available in clinical research industry. We will assist you to decide as to what job profile suits you or you can choose based on your interest. Some of the positions available in the field of clinical research include:

Bioanalytical Positions Business Development

Project Management Quality Control Research Scientist Bioinformatics Clinical Data/Archives Regulatory Affairs Biostatistician Clinical Research Associate Clinical Data management executive Marketing/Public Relation Technician, Skilled Trades Medical Writing Clinical Research Coordinator Clinical Research Investigator and the list continues.

As the phases of Clinical Research progresses from one phase to another, there is a requirement for skilled professionals for trials and documentation. The industry is open to provide lots of opportunities for trained/ certified professionals in various areas such as, Clinical Operations, Site Operations, Clinical Data Management Operations, Medical Writing and much more.

The employers of the industry are looking for trained professionals who have the overall knowledge of industry process.

Additionally, students are trained on the following topics in CliniLead I of Certified Clinical Research Professional (CCRP) course:

1. History of Clinical Research: Takes you through how clinical research started and emerged through to the present standards.

2. Drug Development Process: Explains how a molecule gets isolated from a source, purification process till it reaches the market.

3. Pre-clinical Development: Explains how the drug gets tested on animals. The various stages of pre-clinical development that are mutagenicity, toxicity testing, etc. is discussed in detail.

4. Bioavailability and Bioequivalence (BA-BE): Elaborates on BA-BE studies, which forms a major share of the Clinical Research business in India.

5. Essential clinical trial documents: Provides you with a list of mandatory documents like protocol, investigator brochure (IB), informed consent document,

Investigational product Accountability … etc for a Clinical Research study.

6. Clinical Development: You will learn about all the phases of clinical research in detail.

Today we will be discussing regarding:

Why are ethics necessary in Clinical Research? How the knowledge on ethics in Clinical Research helps

you throughout your career in the industry? What are the regulations followed in Clinical Research? Why is it mandatory for a professional in Clinical

Research to understand the ethics and regulations?

Now let us start with understanding the first question and thereon with history behind each statement/question:

It is mandatory that all the Clinical Research professionals should understand the rules; regulations, and guidelines that govern clinical research internationally. Please go through the trial carried out in USA before specific guidelines (Good Clinical Practice) was set in place and decide for yourself if what happened was ethical or not!

The Tuskegee Syphilis Experiment:

(Reference: http://www.infoplease.com/spot/bhmtuskegee1.html)

Syphilis (sif' u lis) contagious sexually transmitted disease caused by the spirochete Treponema pallidum

For forty years between 1932 and 1972, the U.S. Public Health Service (PHS) conducted an experiment on 399 black men who were in the late stage of syphilis. This study became abusive because it was conducted without any care to its subjects, and led to major changes in how patients are protected in clinical studies. Individuals enrolled in the Tuskegee Syphilis Study were not asked to give informed consent and were not informed of their diagnosis; instead were told they had "bad blood" and could receive “free treatment, a free ride to the clinic, one hot meal per day”, and, in the event of death, $35 (later raised to $50) for the funeral. They were informed that they were being treated for “bad blood,” their doctors had no intention of curing them of syphilis at all.

The data for the experiment was to be collected from autopsies of the men, and the subjects were thus deliberately left to degenerate under the ravages of tertiary syphilis— which can include tumors, heart disease, paralysis, blindness, insanity, and death. “As I see it,” one of the doctors involved explained, “we have no further interest in these patients until they die.”

One of the most chilling fact of this experiment was how zealously the PHS kept these men from receiving treatment. When several nationwide campaigns to eradicate venereal disease came to Macon County, the men were prevented from participating in it. Even when penicillin—the first actual cure for syphilis—was discovered in the 1940s, the Tuskegee men were deliberately denied the medication.

The aftershocks of this study led directly to the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and the National Research Act. This act requires the establishment of Institutional Review Boards (IRBs) at institutions receiving federal grants. Special consideration must be given to ethnic minorities and vulnerable groups in the design of clinical studies.

There were many more studies conducted that were unethical and unregulated, which resulted in human exploitation.

Hence, in other words,

Clinical Trials + Human Beings = Potential for human exploitation

Thus it is mandatory to set ethical standards added with a central body which regulates clinical research carefully.

Q ) Which is important? Is it Regulatory body or ethical body?

Ans ) It is clearly evident that both the ethical bodies and regulatory bodies are important in order to run proper clinical research trails. The ethical parameters set by an ethical body provides ethical guidelines, which is common to all the trials. The regulatory bodies can avoid unethical practices as well as take legal action on personnel involved in improper trials.

It is mandatory that all the Clinical Research professionals should understand the rules; regulations and guidelines that govern clinical research internationally and in their respective countries.

The International Conference of Harmonization (ICH) is a unique international body that's entrusted with making and updating guidelines that bring together the regulatory authorities of Europe, Japan, Canada and the United States. The purpose of this regulation is to achieve greater harmonization in the interpretation and application of technical guidelines and requirements for product registration in order to reduce or eliminate the need to duplicate testing carried out during the research and development of new medicines. The objective of such harmonization is a more ethical and economical use of human, animal and material resources and the elimination of unnecessary delay in launching the same molecule globally while maintaining the safety, efficacy, quality and regulatory obligations of all countries.

What is GCP?

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve human subjects.

Compliance with GCP ensures that the rights, safety and well being of the subjects are protected and that the clinical trial data are credible. These principles have their origin in the Declaration of Helsinki.

The Declaration of Helsinki gives a strong directive on how medical research should be conducted in human beings. This declaration binds all medical researchers to the ethical principles mentioned in the declaration.

Thus following ICH-GCP guidelines (which is an unified standard for US, EU, Japan and Canada) the data generated from the GCP compliant clinical trial will be accepted by the regulatory bodies of all countries that are members of the ICH-GCP council.

Any Clinical Research aspirant who has good knowledge of the ICH-GCP and Schedule Y will be a strong contender to Clinical Research Industry. With this requisite knowledge in Regulations and GCP all aspirants will have a very bright

future in Clinical Research and can be a part of international Clinical Trials (CT).

Given below are the 13 The Principles of ICH-GCP for your reference:

CT - Clinical Trials; QA - Quality Assurance; QC - Quality Control; IEC - Institutional Ethics Committee; IRB - Institutional Review Board; ICH-GCP - International Committee of Harmonization- Good Clinical Practice

DCGI (Drug Control General of India) controls all the aspects of Clinical Trials and approvals of the medicines in India.

Schedule Y:

Schedule Y deals with regulations relating to clinical trial requirements for import, manufacture and obtaining marketing approval for a new drug in India.

Schedule Y contains the forms that need to be used and the data that needs to be collected, as the Investigational product moves from one phase to the other. It also contains the essential clinical trial documents for the trial conducted in India., etc.

You will be learning in detail about the International ethical standards (GCP), Schedule Y, and other ethical and regulatory aspects in Clinilead – II of CCRP

The other topics that you will be learning in CliniLead II are:

Essential Clinical Research Terminology Pre-requisites of the study Ethical and Safety considerations Responsibilities of EC Responsibilities of Sponsor Responsibilities of Monitor Responsibilities of Investigator Record keeping and data handling Documentation process Special concerns Clinical trial of vaccines and phases Clinical trial of contraceptives Clinical trial of medical devices Clinical trial of diagnostic agents Clinical trial of herbal remedies Formats for CT submissions to DCGI Schedule Y Regulations in US, Europe and Australia

Today we will be learning:

What is an organization? How did it come into being?

Services provided by CRO's. Organizational structure - Clinical Operation and Data

Management An insight into the organizational skills, which

accelerates your career growth.

What is an Organization?

The word “organization” is derived from the Greek word organon, which means ‘a tool'. The term is used in both daily and scientific English in multiple ways.

Meaning: The very basic meaning of organization is 'Arrangement'. Organization in terms of career is a group of people intentionally organized to accomplish an overall, common goal or set of goals.

( Carter McNamara, MBA, PhD, Authenticity Consulting, LLC )

As a famous author, John Donne, has written, ‘No man is an Island'. It is difficult for a single person to function at the optimum when alone. He is at his best when around people. Increased manpower means increased business, and vice versa. This is the main reason for the formation of organizations.

For optimal functioning in the field of medical research, Contract Research Organizations (CRO) came into existence.

GCP defines the Contract Research Organization (CRO) as an organization to which the sponsor may transfer or delegate some or all of the tasks, duties and / or obligations regarding a Clinical Study.

Stan W. Woollen, Associate Director for Bioresearch Monitoring from the Office for Good Clinical Practice defines a Site Management Organization (SMO) as a person/ organization that assumes, as an independent contractor with the clinical investigator, one or more of the regulatory obligations of a clinical investigator, e.g., preparation and maintenance of case histories, ensuring compliance with IRB review.

There are a number of positions that are available in a CRO and SMO. Take a look at the diagram given below. This shows

the various departments in the CRO or the departments that the CRO interacts with at regular intervals.

Various departments in CRO industry are as follows:

Medical Writing Quality control and assurance Regulatory affairs Medical monitoring Pharmacovigilance Diagnostic imaging services Data management Analytical department Final report writing

They are constantly in touch with the following bodies:

Data and Safety Management Board Regulatory Body (US FDA, DCGI, etc)

Central laboratory for biological samples.

The basic organizational model of a CRO is as given below:

Basic operational model for Data Management is as given below.

The higher the position you are in, the better you need to be at your organizational skills.

Therefore with right organizational skills, you will be what you want to be in an organization. Gaining the organizational skills not only improves your performance in your designated role, but also triggers a progressive career path.

For instance, let's learn about email writing.

Email Etiquette: - the very basics are to convey a message in clear and concise tone. This is the basic thing that one should know to convey information in an organization setup.

The fist question you need to know before write an email is WHY are you writing. The answer becomes the very first sentence. The reader gets the message in the very first line. The reader is no more searching for the context! A little more in detail:

Correspondence often has a 3-part structure. A simple way to signal this structure to the reader is to use 3 paragraphs, one for each part of the structure.

This 3-part structure will encourage you to write short, concise letters. For example:

Paragraph 1: - Introduction.

It usually deals with the past. It says why the letter has been written.

Paragraph 2: - Development phase.

Updates the reader on the matter and explains the current status of matter. In complex letters this section may be 2 or 3 paragraphs.

Paragraph 3 is the conclusion or outcome.

It foresees a problem or the solution to the existing problem and focuses on action.

Take a look at the example provided below:

Through the Certified Clinical Research Professional course (CCRP), you would also be learning:

Problem Solving Skills Communication skills Email communication Art of questioning Attention to Details Minutes of the meeting Time Management Skills Telephone Etiquettes Presentation Skills Interpersonal Skills - Being a team Player Documentation skills Participating in the meetings Career skills

The above skills are handpicked after consulting the leaders in the industry for the desired skills they are looking at. Learn them and you have an edge – Guaranteed!

Next, in the final part-5 of this online course brings to you a recap of the previous four parts followed by a pre-test which qualifies you to take up CCRP certification.

Do remember that the CCRP course is designed for the industry needs. The goal of InLeaD is to train you to the industry standards. Be prepared to get certified. Our placement cell supports you until you succeed.

Overview of Clinical Research and Careers - Part 5

Thank you for taking this online training course

Greetings from InLeaD (Institute for Learning and Development).

Part 5 takes you back to the history - a recap about the previous 4 parts followed by a simple pre-test which qualifies you to take up CCRP certification.

Just a re-visit to understand the demand of the industry and the need to be trained now:

An estimated 100,000+ clinical trials are carried out throughout the world. Thousands of trials are conducted in India.

CRO's, Pharmaceutical companies, Hospitals and biotech companies need trained professionals to monitor and manage clinical trials.

You will learn the core skills through CCRP course. This can enable you to contribute to the research and allied services teams finding medicals solutions for problems faced by the mankind.

What you have achieved till now:Congratulations you are on the verge of completing the step 1 (this course which you have studied over a week)

Now you have studied regarding the various processes involved in Clinical Trials and drug development process.

You have understood the fundamentals of GCP, principles of GCP and regulatory bodies.

You can appreciate the importance of Organizational skills and the role it can play in your career.

It is now the time to build on the knowledge you have gained. You are one among the special few to enroll and learn the online course. Answer a simple pretest and you become eligible to the full course- the CCRP. CCRP course is offered only to the select few who have the urge to study and gain the industry knowledge. Enroll now and complete the CCRP full course.

That's exactly what the industry needs!

Now is the right time! Yes, the Clinical Research Industry is booming. This growing stage of the industry always provides great career opportunities and growth at a good pace.

Now that you have completed the free short course in clinical research, Please open the pretest(word.doc), answer and send the soft copy to ccrp@crocareers.in

** Download the Pre-test here. Click here.

CCRP is an intensive, industry-recognized course, which enables you as a potential candidate for the Clinical Research Industry and assists you in the selection process.

Once you have completed the course, you get certified and your CCRP qualified resume is uploaded on to our

web site www.crocareers.in. The list of Clinical Research Employers seeking CCRP's is growing day by day!

Additionally, we strongly promote your profile through our network of placement consultants and assist you in choosing the right career.

All you need now is a good training. Once you get recognized as a Certified Clinical Research Professional (CCRP), you are just not trained but also viewed by top employers.CCRP course training is flexible and suits your day-to day activities. Be a better contender for an exciting Clinical Research position in just 6 weeks!

All you have to do is follow the steps below:

First: Please mail the answered pretest to Mail-id: ccrp@crocareers.in

Second: Join the CCRP course.