Promising scope for Bangladesh to become a leader in clinical research trials
Wednesday, 20 February 2008
Jakey Uddin Ahmed Patwari, MD, CCRC
BECAUSE of several advantages and advancement of clinical trials, pharmaceutical and device companies of many countries in Asia, are sponsoring multi-national, multi-center clinical trials in the USA and EU to obtain Federal Drug Administration (FDA) and EU approval of their new drugs and devices, so they can market their products all over the world, especially in the USA, Canada and EU.
In this context, Bangladesh can also be a superpower in performing clinical research trials. It can use India, China, Singapore, Malayasia, Thailand and Israel as a model for rapid growth in clinical trials industry.
Drug Development Process: Drug Development is a time consuming process. Most of the compounds do not complete the process and is a costly investment.
About 10,000 chemical or biological compounds are screened in the laboratory, of which 25 reach the non-clinical studies (which do not involve human participants), five reach clinical studies, and finally one receives approval for marketing. It takes 10 years for a drug being tested to reach preclinical studies and total 20 years to get it approved.
According to Tufts Center for the Study of Drug Development (TCSDD) in 2003 the average cost of developing a drug was $897 million and in 2006 it has reached $1.2 billion.
This estimate includes the time value of each dollar invested and assigns the cost of failed compounds to drugs that obtain regulatory approval. Only one out of three approved drugs entering the market ever recoups its total Research & Development (R&D) investment.
Clinical Trials: A clinical trial is a research study to find answers to specific questions about vaccines, new drugs, therapies, devices or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in humans. Participants in clinical trials can play a more active role in their own healthcare, gain access to new research treatments before they are widely available, and help others by contributing to medical research.
Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may work.
Clinical trials are sponsored or funded by a variety of organisations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to the US federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA).
A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial -- the schedule of tests, procedures, medications, and dosages, and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.
A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment.
A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo. Treatment trials test new 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. 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
Non-clinical research refers to studies that do not involve human participants. The objectives of non-clinical studies are to provide information on safety and, if possible efficiency, in order to begin clinical studies on humans. The information received from non-clinical studies provides the pharmaceutical company, the FDA, and the IRB with enough evidence to make reasonable decisions about the compound.
The information required for Investigational New Drug (IND) application includes: data on acute toxicity, data for some repeat dose toxicity studies, some genotoxicity studies, the kinetics and metabolism of the drug, organ sensitivity, the starting dose with acceptable range of safety and efficacy for human subjects, route of administration, dosing and duration of Phase I.
In the USA, the FDA becomes involved in the drug development programme at the point when the sponsor has completed sufficient non-clinical work with the compound to determine that it is safe for human usage and is reasonable to start working with humans.
As a result, the molecule changes its legal status under the Federal Food, Drug, and Cosmetic Act. It becomes a new drug and is subject to specific regulatory requirements. In order to start human testing, the sponsor must file an IND with the FDA. INDs are not actively approved by the FDA, but may be disapproved or placed on clinical hold. If the company has not heard from the FDA, clinical testing of the new compound may begin within thirty days after the FDA has received the IND. Even though it is not required, most companies will still contact the FDA if they have not heard within thirty days, just to verify that the FDA is in agreement about starting human studies (Phase I).
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 new drug or treatment in a small group (20-80) of healthy volunteers except cancer and HIV trials, for testing them for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Volunteers are exposed to the drug for a short period of time (few days).
In Phase II trials, the study drug or treatment is given to a larger group of patients (100-300) to see if it is effective and to further evaluate its safety of the compound (drug). Study patients are exposed to the drugs for few weeks.
In Phase III trials, the study drug or treatment is given to large groups of patients (1,000-3,000) to confirm its effectiveness, monitor side-effects, compare the same to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Study patients are exposed to the drugs for few months.
In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use. Study patients are exposed to the drugs for months to years.
Before a clinical trial can be conducted, several events must occur. First and foremost, a drug company must first develop a new drug or treatment option, which is a very extensive process. The authenticity of a clinical trial and its success or failure directly depends on the review of FDA or drug evaluation authority, reviewed by Independent Review Board (IRB), Ethics Committee (EC), and audit by sponsor and regulatory agencies or FDA.
Challenges for Bangladesh: The World Bank says more than 60% of Bangladeshis, about 80 million people, have no access to modern health services other than immunization and family planning.
Bangladesh, however, faces real challenges. Its large treatment-naïve population is extremely desirable. However, healthcare infrastructure in Bangladesh needs to be improved. Massive improvement is required in government and for investigators and study volunteers. The government needs to understand the vulneribility of the population and requires to establish and enforce GCP-ICH regulation, formation and to oversee the Independent Review Board (IRB), Ethics Committee (EC), intellectual property law. In theis industry, physicians and patients steaks are very significant. Physcians and investigators must educate themselves about clinical investigations.
Most of the time they fail to distingusih difference between clinical research and clinical practice. They have have paramount responsibilities such as training of GCP-ICH regulation, local and national regulations, human subject protection, clinical trials in general and specific study protocol. The investigators are also responsible for training and supervising of subinvestigators and all study personnel. For patients and family local social concers, political, cultural and economic motivation is warranted. Language barrier has serious impact in clinical trials, which needs to improve. Overall, there is great deal of potential in this nation.
The writer is a Bangladeshi physician working in clinical research industry in the USA and have been serving many famous organisations there for the last 15 years. Concluded
BECAUSE of several advantages and advancement of clinical trials, pharmaceutical and device companies of many countries in Asia, are sponsoring multi-national, multi-center clinical trials in the USA and EU to obtain Federal Drug Administration (FDA) and EU approval of their new drugs and devices, so they can market their products all over the world, especially in the USA, Canada and EU.
In this context, Bangladesh can also be a superpower in performing clinical research trials. It can use India, China, Singapore, Malayasia, Thailand and Israel as a model for rapid growth in clinical trials industry.
Drug Development Process: Drug Development is a time consuming process. Most of the compounds do not complete the process and is a costly investment.
About 10,000 chemical or biological compounds are screened in the laboratory, of which 25 reach the non-clinical studies (which do not involve human participants), five reach clinical studies, and finally one receives approval for marketing. It takes 10 years for a drug being tested to reach preclinical studies and total 20 years to get it approved.
According to Tufts Center for the Study of Drug Development (TCSDD) in 2003 the average cost of developing a drug was $897 million and in 2006 it has reached $1.2 billion.
This estimate includes the time value of each dollar invested and assigns the cost of failed compounds to drugs that obtain regulatory approval. Only one out of three approved drugs entering the market ever recoups its total Research & Development (R&D) investment.
Clinical Trials: A clinical trial is a research study to find answers to specific questions about vaccines, new drugs, therapies, devices or new ways of using known treatments. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in humans. Participants in clinical trials can play a more active role in their own healthcare, gain access to new research treatments before they are widely available, and help others by contributing to medical research.
Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may work.
Clinical trials are sponsored or funded by a variety of organisations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to the US federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA).
A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial -- the schedule of tests, procedures, medications, and dosages, and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.
A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment.
A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo. Treatment trials test new 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. 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
Non-clinical research refers to studies that do not involve human participants. The objectives of non-clinical studies are to provide information on safety and, if possible efficiency, in order to begin clinical studies on humans. The information received from non-clinical studies provides the pharmaceutical company, the FDA, and the IRB with enough evidence to make reasonable decisions about the compound.
The information required for Investigational New Drug (IND) application includes: data on acute toxicity, data for some repeat dose toxicity studies, some genotoxicity studies, the kinetics and metabolism of the drug, organ sensitivity, the starting dose with acceptable range of safety and efficacy for human subjects, route of administration, dosing and duration of Phase I.
In the USA, the FDA becomes involved in the drug development programme at the point when the sponsor has completed sufficient non-clinical work with the compound to determine that it is safe for human usage and is reasonable to start working with humans.
As a result, the molecule changes its legal status under the Federal Food, Drug, and Cosmetic Act. It becomes a new drug and is subject to specific regulatory requirements. In order to start human testing, the sponsor must file an IND with the FDA. INDs are not actively approved by the FDA, but may be disapproved or placed on clinical hold. If the company has not heard from the FDA, clinical testing of the new compound may begin within thirty days after the FDA has received the IND. Even though it is not required, most companies will still contact the FDA if they have not heard within thirty days, just to verify that the FDA is in agreement about starting human studies (Phase I).
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 new drug or treatment in a small group (20-80) of healthy volunteers except cancer and HIV trials, for testing them for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. Volunteers are exposed to the drug for a short period of time (few days).
In Phase II trials, the study drug or treatment is given to a larger group of patients (100-300) to see if it is effective and to further evaluate its safety of the compound (drug). Study patients are exposed to the drugs for few weeks.
In Phase III trials, the study drug or treatment is given to large groups of patients (1,000-3,000) to confirm its effectiveness, monitor side-effects, compare the same to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Study patients are exposed to the drugs for few months.
In Phase IV trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use. Study patients are exposed to the drugs for months to years.
Before a clinical trial can be conducted, several events must occur. First and foremost, a drug company must first develop a new drug or treatment option, which is a very extensive process. The authenticity of a clinical trial and its success or failure directly depends on the review of FDA or drug evaluation authority, reviewed by Independent Review Board (IRB), Ethics Committee (EC), and audit by sponsor and regulatory agencies or FDA.
Challenges for Bangladesh: The World Bank says more than 60% of Bangladeshis, about 80 million people, have no access to modern health services other than immunization and family planning.
Bangladesh, however, faces real challenges. Its large treatment-naïve population is extremely desirable. However, healthcare infrastructure in Bangladesh needs to be improved. Massive improvement is required in government and for investigators and study volunteers. The government needs to understand the vulneribility of the population and requires to establish and enforce GCP-ICH regulation, formation and to oversee the Independent Review Board (IRB), Ethics Committee (EC), intellectual property law. In theis industry, physicians and patients steaks are very significant. Physcians and investigators must educate themselves about clinical investigations.
Most of the time they fail to distingusih difference between clinical research and clinical practice. They have have paramount responsibilities such as training of GCP-ICH regulation, local and national regulations, human subject protection, clinical trials in general and specific study protocol. The investigators are also responsible for training and supervising of subinvestigators and all study personnel. For patients and family local social concers, political, cultural and economic motivation is warranted. Language barrier has serious impact in clinical trials, which needs to improve. Overall, there is great deal of potential in this nation.
The writer is a Bangladeshi physician working in clinical research industry in the USA and have been serving many famous organisations there for the last 15 years. Concluded