Tuesday, October 23, 2018

INTRODUCTION TO CLINICAL RESEARCH - pharmacovigilance-material


INTRODUCTION TO CLINICAL RESEARCH

Clinical trials have revolutionised the way disease is prevented, detected or treated and early death avoided. They continue to be an expanding area of research. They are central to the work of pharmaceutical companies, which cannot make a claim about a new drug or medical device until there is sufficient evidence on its efficacy. Trials originating from the academic or public sector are more common because they also evaluate existing therapies in different ways or interventions that do not involve a commercial product. Many health care professionals are expected to conduct their own trials or to participate in trials by recruiting subjects. They should have a sufficient understanding of the scientific and administrative aspects, including an awareness of the regulations and guidelines associated with clinical trials, which are now more stringent in many countries, making it more difficult to set up and run trials.
Early construction of a Clinical Trial:
James Lind, a Scottish naval physician, has conducted the first clinical trial. During a sea voyage in 1747, he chose 12 sailors with similarly severe cases of scurvy and examined six treatments, each given to two sailors. They were cider, diluted sulphuric acid, vinegar, seawater, a mixture of several foods including nutmeg and garlic, and oranges and lemons. They were made to live in the same part of the ship and with the same basic diet. Lind felt it was important to standardise their living conditions to ensure that any change in their disease is unlikely to be due to other factors. After about a week, both sailors given fruit had almost completely recovered, compared to little or no improvement in the other sailors. This dramatic effect led Lind to conclude that eating fruit was essential to cure scurvy, without knowing that it was specifically due to vitamin C. The results of his trial were supported by observations made by other seamen and physicians.
Lind had little doubt about the value of fruit. Two important features of his trial were: a comparison between two or more interventions and an attempt to ensure that the subjects had similar characteristics.  The requirement for these two features has not changed and it is an indication that how important they are in conducting good trials that aim to provide reliable answers.
Fundamental concepts:
There are two distinct study designs used in health research: observational and experimental. Observational studies do not intentionally involve intervening in the way individuals live their lives or how they are treated. However, clinical trials are specifically designed to intervene and then evaluate some health-related outcome with one or more of the following:
·          to diagnose or detect disease
·          to treat an existing disorder
·          to prevent disease or early death
·          to change behavior, habits or other lifestyle factors
Some trials evaluate new drugs or medical devices that will later require a licence (or marketing authorisation) for human use from a regulatory authority, if a benefit is shown. This allows the treatment to be marketed and routinely available to the public.
Other trials are based on therapies that are already licensed, but will be used in different ways, such as a different disease group or in combination with other treatments. An intervention could be a single treatment or therapy namely an administered substance that is injected, swallowed, inhaled or absorbed through the skin, an exposure such as radiotherapy, a surgical technique or a medical dental device. A combination of interventions can be referred to as a regimen, such as, chemotherapy plus surgery in treating cancer. Other interventions could be educational or behavioural programmes or dietary changes.
Any administered drug or micronutrient that is examined in a clinical trial with the specific purpose of treating, preventing or diagnosing disease is usually referred to as an Investigational Medicinal Product (IMP) or Investigational New Drug (IND). An IMP could be a newly developed drug or one that is already licensed for human use. Most clinical trial regulations that are part of law in several countries cover studies using an IMP and sometimes medical devices.
What Is a Clinical Study?
A clinical study involves research using human volunteers (also called participants) that is intended to add to medical knowledge. There are two main types of clinical studies: clinical trials and observational studies. Clinical Trials includes both interventional and observational studies.
Clinical Trials
In a clinical trial (also called an interventional study), participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or changes to participants' behavior, for example, diet. Clinical trials may compare a new medical approach to a standard one that is already available or to a placebo that contains no active ingredients or to no intervention. Some clinical trials compare interventions that are already available to each other. When a new product or approach is being studied, it is not usually known whether it will be helpful, harmful, or no different than available alternatives (including no intervention). The investigators try to determine the safety and efficacy of the intervention by measuring certain outcomes in the participants. For example, investigators may give a drug or treatment to participants who have high blood pressure to see whether their blood pressure decreases.
Clinical trials used in drug development are sometimes described by phase. These phases are defined by the Food and Drug Administration (FDA).
Note: Some people who are not eligible to participate in a clinical trial may be able to get experimental drugs or devices outside of a clinical trial through an Expanded Access Program. See more information on expanded access from the National Library of Medicine.
Observational Studies
In an observational study, investigators assess health outcomes in groups of participants according to a protocol or research plan. Participants may receive interventions, which can include medical products, such as drugs or devices, or procedures as part of their routine medical care, but participants are not assigned to specific interventions by the investigator (as in a clinical trial). For example, investigators may observe a group of older adults to learn more about the effects of different lifestyles on cardiac health.
Who Conducts Clinical Studies?
Every clinical study is led by a principal investigator, who is often a medical doctor. Clinical studies also have a research team that may include doctors, nurses, social workers, and other health care professionals. Clinical studies can be sponsored, or funded, by pharmaceutical companies, academic medical centers, voluntary groups, and other organizations, in addition to Federal agencies such as the National Institutes of Health, U.S. Department of Defense, and U.S. Department of Veterans Affairs. Physicians, health care providers, and other individuals can also sponsor clinical research.
Where Are Clinical Studies Conducted?
Clinical studies can take place in many locations, including hospitals, universities, doctors' offices, and community clinics. The location depends on who is conducting the study.
How Long Do Clinical Studies Last?
The length of a clinical study varies, depending on what is being studied. Participants are told how long the study will last before enrolling.
Reasons for Conducting Clinical Studies
In general, clinical studies are designed to add to medical knowledge related to the treatment, diagnosis, and prevention of diseases or conditions. Some common reasons for conducting clinical studies include:
                     Evaluating one or more interventions (for example, drugs, medical devices, approaches to surgery or radiation therapy) for treating a disease, syndrome, or condition
                     Finding ways to prevent the initial development or recurrence of a disease or condition. These can include medicines, vaccines, or lifestyle changes, among other approaches.
                     Evaluating one or more interventions aimed at identifying or diagnosing a particular disease or condition
                     Examining methods for identifying a condition or risk factors for that condition
                     Exploring and measuring ways to improve the comfort and quality of life of people with a chronic illness through supportive care
Participating in Clinical Studies
A clinical study is conducted according to a research plan known as the protocol. The protocol is designed to answer specific research questions as well as safeguard the health of participants. It contains the following information:
           The reason for conducting the study
           Who may participate in the study (the eligibility criteria?)
           The number of participants needed
           The schedule of tests, procedures, or drugs and their dosages
           The length of the study
           What information will be gathered about the participants?
Who Can Participate in a Clinical Study?
Clinical studies have standards outlining who can participate, called eligibility criteria, which are listed in the protocol. Some research studies seek participants who have the illnesses or conditions that will be studied. Other studies are looking for healthy participants. And some studies are limited to a predetermined group of people who are asked by researchers to enroll.
Eligibility. The factors that allow someone to participate in a clinical study are called inclusion criteria, and the factors that disqualify someone from participating are called exclusion criteria. These are based on things such as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions.
How Are Participants Protected?
Informed consent is a process in which researchers provide potential and enrolled participants with information about a clinical study. This information helps people decide whether they want to enroll, or continue to participate, in the study. The informed consent process is intended to protect participants and should provide enough information for a person to understand the risks of, potential benefits of, and alternatives to the study. In addition to the informed consent document, the process may involve recruitment materials, verbal instructions, question-and- answer sessions, and activities to measure participant understanding. In general, a person must sign an informed consent document before entering a study to show that he or she was given information on risks, potential benefits, and alternatives and understands it. Signing the document and providing consent is not a contract. Participants may withdraw from a study at any time, even if the study is not over. See Questions to Ask a health care provider or researcher about participating in a clinical study.
Institutional review boards. Each federally supported or conducted clinical study and each study of a drug, biological product, or medical device regulated by FDA must be reviewed, approved, and monitored by an institutional review board (IRB). An IRB is made up of physicians, researchers, and members of the community. Its role is to make sure that the study is ethical and the rights and welfare of participants are protected. This includes making sure that research risks are minimized and are reasonable in relation to any potential benefits, among other things. The IRB also reviews the informed consent document.
In addition to being monitored by an IRB, some clinical studies are also monitored by data monitoring committees (also called data safety and monitoring boards).
Various Federal agencies, including the Office of Human Subjects Research Protection (OHRP) and FDA, have the authority to determine whether sponsors of certain clinical studies are adequately protecting research participants.
Relationship to Usual Health Care
Typically participants continue to see their usual health care providers while enrolled in a clinical study. While most clinical studies provide participants with medical products or interventions related to the illness or condition being studied, they do not provide extended or complete health care. By having the participant's usual health care provider work with the research team, the participant can make sure that the study protocol will not conflict with other medications or treatments being received.
Considerations for Participation
Participating in a clinical study contributes to medical knowledge. The results of these studies can make a difference in the care of future patients by providing information about the benefits and risks of therapeutic, preventative, or diagnostic products or interventions.
Clinical trials provide the basis for the development and marketing of new drugs, biological products, and medical devices. Sometimes, the safety and the effectiveness of the experimental approach or use may not be fully known at the time of the trial. Some trials may provide participants with the prospect of receiving direct medical benefits, while others do not. Most trials involve some risk of harm or injury to the participant, although it may not be more than the risks related to routine medical care or disease progression. (For trials approved by IRBs, the IRB has decided that the risks of participation have been minimized and are reasonable in relation to anticipated benefits.) Many trials require participants to undergo additional procedures, tests, and assessments based on the study protocol. These will be described in the informed consent document for a particular trial. A potential participant should also discuss these issues with members of the research team and with his or her usual health care provider.
Questions to Ask
Anyone interested in participating in a clinical study should know as much as possible about the study and feel comfortable asking the research team questions about the study, the related procedures, and any expenses. The following questions might be helpful during such a discussion. Answers to some of these questions are provided in the informed consent document. Many of these questions are specific to clinical trials, but some also apply to observational studies.
                     What is being studied?
                     Why do researchers believe the intervention being tested might be effective? Why might it not be effective? Has it been tested before?
                     What are the possible interventions that I might receive during the trial?
                     How will it be determined which interventions I receive (for example, by chance)?
                     Who will know which intervention I receive during the trial? Will I know? Will members of the research team know?
                     How do the possible risks, side effects, and benefits of this trial compare with those of my current treatment?
                     What will I have to do?
                     What tests and procedures are involved?
                     How often will I have to visit the hospital or clinic?
                     Will hospitalization be required?
                     How long will the study last?
                     Who will pay for my participation?
                     Will I be reimbursed for other expenses?
                     What type of long-term follow-up care is part of this trial?
                     If I benefit from the intervention, will I be allowed to continue receiving it after the trial ends?
                     Will results of the study be provided to me?
                     Who will oversee my medical care while I am in the trial?
                     What are my options if I am injured during the study?

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INTRODUCTION TO CLINICAL RESEARCH - pharmacovigilance-material

INTRODUCTION TO CLINICAL RESEARCH Clinical trials have revolutionised the way disease is prevented, detected or treated and early deat...