LIGHTENING TOWARDS CLINICAL TRIAL A REVIEW

LIGHTENING TOWARDS CLINICAL TRIAL

A REVIEW

K. T. ShameelHH, Rahul Soman

National College of Pharmacy, Manassery, Calicut

Cite this: K. T. Shameel, Rahul Soman, "LIGHTENING TOWARDS CLINICAL TRIAL A REVIEW", B. Pharm Projects and Review Articles, Vol. 1, pp. 1635-1679, 2006. (http://farmacists.blogspot.in/)

 

INTRODUCTION

 

    Clinical trials, also known as clinical studies, are research studies in which scientists and doctors test new drugs and treatments to see if they will improve health. Many of today's treatments for cancer are based on the results of past clinical trials. Because of progress made through clinical trials, many people treated for cancer are now living longer. Clinical trials are divided into four phases.

 

WORLD HEALTH ORGANISATION DEFINITION

    According to the World Health Organisation (WHO), a clinical trial is ' Any research project that prospectively assigns human participants or groups to one or more health-related interventions to evaluate the effects on health outcomes.'

 

CLASSIFICATION OR DIFFERENT TYPE OF CLINICAL TRIAL

There are several types of clinical trials:

• Prevention trials test new approaches, such as medications, vitamins, or other supplements, that doctors believe may lower the risk of developing a certain type of cancer. Most prevention trials are conducted with healthy people who have not had cancer. Some trials are conducted with people who have had cancer and want to prevent recurrence (return of cancer), or reduce the chance of developing a new type of cancer.
• Screening trials study ways to detect cancer earlier. They are often conducted to determine whether finding cancer before it causes symptoms decreases the chance of dying from the disease. These trials involve people who do not have any symptoms of cancer.
• Diagnostic trials
  study tests or procedures that could be used to identify cancer more accurately. Diagnostic trials usually include people who have signs or symptoms of cancer.
• Treatment trials are conducted with people who have cancer. They are designed to answer specific questions about, and evaluate the effectiveness of, a new treatment or a new way of using a standard treatment. These trials test many types of treatments, such as new drugs, vaccines, new approaches to surgery or radiation therapy, or new combinations of treatments.
• Quality-of-life (also called supportive care) trials explore ways to improve the comfort and quality of life of cancer patients and cancer survivors. These trials may study ways to help people who are experiencing nausea, vomiting, sleep disorders, depression, or other effects from cancer or its treatment.
• Genetics studies are sometimes part of another cancer clinical trial. The genetics component of the trial may focus on how genetic makeup can affect detection, diagnosis, or response to cancer treatment.

 

DESIGNING OF CLINICAL TRIAL OBJECTIVES

 

Before going detailing into the other aspects of clinical trial, it is a must to know about the several aspects of clinical trials like

1. protocol and its development with expanded acess protocol
2. role of ethics
3. participants criteria
4. eligibility criteria
5. informed consent
6. placebo
7. control and control group
8. safety of participants
9. sponsors
10. place of clinical trials
11. do consider before participating in a trial

 

Protocol and its development

What is a protocol? Clinical trials use written guidelines called protocols. The protocol explains what the trial hopes to accomplish, how the trial will be carried out, and why each part of the trial is necessary. For example, the protocol includes:

• The reason for doing the trial
• How many people will be in the trial
• Who is eligible to take part in the trial
• What study drugs participants will need to take
• What medical tests participants will have and how often
• What information will be gathered

    Protocols are written by the trial sponsors (those conducting the trial) and must first be reviewed by an Institutional Review Board (IRB) at each participating hospital or medical center before they can begin. IRBs are committees that oversee the safety of people who take part in clinical trials.

 

Protocol and its development

 

    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.

 

Ethics Committees


 

    An ethics committee must approve every survey or experiment a psychologist wishes to run. It is important to obtain ethical approval for each survey to ensure that the questions asked are appropriate and do not cause people offence.

 

    Participants in psychological research should have confidence in the researchers. They should be supplied with all the relevant information about the study, the method of data gathering (e.g. questionnaire, computer test), the sample group (students, children, general public) and the object of the research.

 

    The British Psychological Society has a 'code of conduct' to guide psychologists in their research. The code sets out certain standards which psychologists are required to comply with.

• Researchers must consider the ethical implications and psychological consequences for the participants in their research. Threats to their psychological well-being, health, values or dignity should be removed.
• The researcher should inform all participants of all aspects of the research.
• The withholding of information or the misleading of participants is unacceptable if the participants are likely to object or show unease once debriefed.
• Participants should know their right to withdraw from the research at any time.
• Information obtained about a participant during an investigation is confidential unless otherwise agreed in advance.
• Researchers have a primary responsibility to protect participants from physical and mental harm during the investigation.

 

    Ethics committees must also be informed of all aspects of the research. They too should be supplied with all the relevant information about the study, the method of data gathering the sample group and the object of the research.

 

    Ethics committees review the research and provide advice to ensure the research meets the required ethical standards. The purpose of an ethics committee is to protect the dignity, rights, safety and well being of the individuals involved.

 
    Research Ethics Committees (RECs) are independent groups, founded and governed by local Health Authorities or the Department of Health. Research cannot be started until the Research Ethics Committees has given its approval.

 

PARTICIPANTS CRITERIA

• Sometimes participating in clinical trials may allow patients
  to receive experimental treatments, especially when they have
  a disease that has not responded to other therapies.
  
  
• All participants
  in clinical trials are volunteers who can withdraw
  from a trial
  if they choose.
  
  
• Participants should have the option to review
  the purpose and
  design of the study and understand whether control
  participants
  will receive standard therapy or placebo.
  
  
• Participants
  should have all their questions answered before
  agreeing to
  participate in a clinical trial.
  
  
• If you are thinking of joining
  a clinical trial, discuss participation
  with your doctor to
  be sure it fits with your ongoing care.
  
  

ELIGIBILITY CRITERIA

    Each study protocol has guidelines for who can or cannot participate in the study. These guidelines, called eligibility criteria, describe characteristics that must be shared by all participants. The criteria differ from study to study. They may include age, gender, medical history, and current health status. Eligibility criteria for treatment studies often require that patients have a particular type and stage of cancer.

 

    Enrolling participants with similar characteristics helps to ensure that the results of the trial will be due to what is under study and not other factors. In this way, eligibility criteria help researchers achieve accurate and meaningful results. These criteria also minimize the risk of a person condition becoming worse by participating in the study.

 

INFORMED CONSENT

    Informed consent is a process by which people learn the important facts about a clinical trial to help them decide whether to participate. This information includes details about what is involved, such as the purpose of the study, the tests and other procedures used in the study, and the possible risks and benefits. In addition to talking with the doctor or nurse, people receive a written consent form explaining the study. People who agree to take part in the study are asked to sign the informed consent form. However, signing the form does not mean people must stay in the study. People can leave the study at any time" either before the study starts or at any time during the study or the follow-up period.

    The informed consent process continues throughout the study. If new benefits, risks, or side effects are discovered during the study, the researchers must inform the participants. They may be asked to sign new consent forms if they want to stay in the study.

 

Placebo

    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 experimental treatment's effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or experimental treatment.

 

Control or Control Group

    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.

 

SAFETY OF PARTICIPANTS

 

    During the trial, review committees such as Institutional Review Boards (IRBs), make sure that the plan is being followed and participants are being protected. Researchers performing studies are required by law to inform patients about a study's treatment and their possible benefits and risks before a patient decides whether to take part in the study. This process is called informed consent

 

    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

SPONSORS

• Government agencies, such as the National Cancer Institute (NCI) and other parts of the National Institutes of Health (NIH), the Department of Defense, and the Department of Veterans Affairs, sponsor and conduct clinical trials. In addition, organizations or individuals, such as physicians, medical institutions, foundations, volunteer groups, and pharmaceutical companies, also sponsor clinical trials.
  
  NCI sponsors a large number of clinical trials and has a number of programs designed to make clinical trials widely available in the United States. These programs include the following:
  • The Cancer Centers Program provides support to research-oriented institutions, including those that have been designated as NCI Comprehensive or Clinical Cancer Centers for their scientific excellence. More information is available in the NCI fact sheet The National Cancer Institute Cancer Centers Program, which is available on the Internet.
  • The Specialized Programs of Research Excellence (SPOREs) bring together scientists and researchers to design and implement research programs that can improve prevention, detection, diagnosis, and treatment of specific types of cancer. More information about SPOREs is available on the Internet.
  • The Clinical Trials Cooperative Group Program brings researchers, cancer centers, and doctors together into cooperative groups. These groups work with the NCI to identify important questions in cancer research, and design and conduct multisite clinical trials to answer these questions. Cooperative groups are located throughout the United States and in Canada and Europe. For more information, refer to the fact sheet NCI’s Clinical Trials Cooperative Group Program on the Internet.
  • The Cancer Trials Support Unit (CTSU) makes NCI-sponsored phase III treatment trials available to doctors and patients in the United States and Canada . Doctors who are not affiliated with an NCI-sponsored Clinical Trials Cooperative Group (see above) must complete an application process, which includes credential verification and site preparedness assessment, to become members of the CTSUs National Network of Investigators. CTSU members can enroll patients in clinical trials through the programs Web site, which is located at on the Internet. General information about the CTSU is also available on the programs Web site, or by calling.
  • The Community Clinical Oncology Program (CCOP) makes clinical trials available in a large number of communities across the United States. Local hospitals throughout the country affiliate with a cancer center or a cooperative group. This affiliation allows doctors to offer people participation in clinical trials more easily, so they do not have to travel long distances or leave their usual caregivers. The Minority-Based Community Clinical Oncology Program focuses on encouraging minority populations to participate in clinical trials. More information about the CCOP can be found in the NCI fact sheet Community Clinical Oncology Program: Questions and Answers, which is available on the Internet.
  • The National Institutes of Health Clinical Center, a research hospital located in Bethesda, Maryland, is part of the NIH. Trials at the Clinical Center are conducted by the components of the NIH, including the NCI. The NCI fact sheet Cancer Clinical Trials at the National Institutes of Health Clinical Center: Questions and Answers has more information about the Clinical Center. This fact sheet is available on the Intern

 

Places of clinical trials

    Depending on the type of trial, patients may be treated at one or hundreds of clinical sites at the same time. Clinical sites can include large specialty treatment centers, university hospitals, local medical centers or a doctor's office. Each patient takes part in the trial under the guidance of a team including his/her own doctor and other health care professionals, who report the patient's experience back to the center responsible for the trials' overall coordination. Experts then use the information from all participants to see if the treatment being tested is safe and effective.

 

Do consider before participating in a trial

    People should know as much as possible about the clinical trial and feel comfortable asking the members of the health care team questions about it, the care expected while in a trial, and the cost of the trial. The following questions might be helpful for the participant to discuss with the health care team. Some of the answers to these questions are found in the informed consent document.

• What is the purpose of the study?
• Who is going to be in the study?
• Why do researchers believe the experimental treatment being tested may be effective? Has it been tested before?
• What kinds of tests and experimental treatments are involved?
• How do the possible risks, side effects, and benefits in the study compare with my current treatment?
• How might this trial affect my daily life?
• How long will the trial last?
• Will hospitalization be required?
• Who will pay for the experimental treatment?
• Will I be reimbursed for other expenses?
• What type of long-term follow up care is part of this study?
• How will I know that the experimental treatment is working? Will results of the trials be provided to me?
• Who will be in charge of my care?

 

DIFFERENT PHASES OF CLINICAL TRIALS

 

Phase I trials: These trials are the first time a new drug or treatment is given to humans. They are normally carried out in a small number of volunteers (typically 6-20 people) who may include healthy volunteers or patients with the disease for which the product is intended as a treatment in order to find out how safe the treatment is. They also look at how a new drug should be given (by mouth, injected into muscle or the bloodstream, etc.), how often and at what dose. Phase I trials can also involve patients for whom standard therapies have failed and for whom no other therapies are available.

 

Phase II trials: These trials involve larger numbers of people (typically 12 - 50). Phase II trials continue to look at safety of the therapy but also test how well the new drug or treatment works in patients with different disease types.

 

Phase III trials: These are large studies (100+ people) that look at how well a new drug or treatment works in comparison to current therapies to see which treatment is better. Those taking part are usually divided into two treatment groups: standard treatment versus new treatment.

 

Phase IV trials: These trials are usually carried out after the drug or treatment has been approved by the FDA and is readily available for use in the general patient population. The purpose of Phase IV trials is to continue to study the effects of the drug or treatment on different populations and to look for side effects associated with long-term use.

 

 
What happens during a clinical trial?
If you decide to participate in a clinical trial, you will work with a research team. Team members may include doctors, nurses, social workers, and other health care professionals. They will provide your care, monitor your health carefully, and give you specific instructions about the study.

Taking part in a trial may mean that you will have more tests and doctor visits than you would if you weren't in the study. Team members also may continue to stay in contact with you after the trial ends. To make the trial results as reliable as possible, it is important for participants to follow the research team's instructions. That means having all doctor visits and tests, taking medicines on time, and completing logs or answering questionnaires.

What happens when a clinical trial is over?
After a Phase I or II trial is completed, the researchers look carefully at the data collected during the trial and decide whether to:

• Move on to the next phase trial with the treatment, or
• Stop testing the treatment because it is not sufficiently safe or effective
  

When a Phase III trial is completed, the results maybe submitted to the FDA to consider whether to approve the new treatment for commercial sale.

What are the potential risks and benefits of clinical trials?
Potential benefits include:

• Access to investigational new drugs and therapies before they are available on the market
  
• A more active role in your own health care
  
• Close monitoring of your health care and any side effects
  
• An opportunity to make a valuable contribution to medical research
  

Potential risks include:

• Investigational new drugs and therapies may have unknown side effects
  
• Side effects may be worse than with standard therapies
  
• Even if the approach has benefits, it may not work for you
  

What is informed consent?
Informed consent is a process in which a patient learns all the key facts about the clinical trial before deciding whether to take part. A doctor or research nurse may explain all that is involved. In addition, these facts will be given to you in a written consent form that you may take home to read and discuss. The consent form will included details about:

• The study approach
  
• The possible risks and benefits
  
• The tests and procedures you will have if you take part
  

Patients interested in taking part are encouraged to ask questions until they have all the information needed. Informed consent continues as long as you are in the study. You may change your mind at any time and leave the study whenever you want. Should you wish to stop participating in the study, standard therapy will remain available to you.

Who pays for the patient costs on a clinical trial?
Even if you have health insurance, your coverage may not include some or all of the costs associated with a clinical trial. This is because some health care plans view clinical trials as 'experimental' or 'investigational' procedures. The National Cancer Institute (NCI) is working with major health care providers to find a solution to this coverage problem.

For Vical studies, Vical will be responsible for providing the study drug and for all evaluations, scans, and treatments required by your participation in the study. Either you or your insurance company will be billed for any routine medical care for problems or complications of your disease unrelated to the administration of the study drug. This includes routine blood tests, x-rays, scans, medications and physician charges.

You will not be paid for participation in any study. Your doctor will make available or arrange for appropriate care and treatment for any physical injury resulting directly from participating in the study.

Who is eligible to take part in a clinical trial?
Each study has guidelines for who can take part. These are called eligibility criteria. Generally those who take part in the study are alike in certain aspects such as type and stage of disease, age, gender or previous treatments. The eligibility criteria are included in the study plan (also called a protocol).

What are your rights if you take part in a clinical trial?
Taking part in a study is voluntary. You may choose not to take part or may leave the study at any time. Leaving the study will not result in any penalty or loss of benefits to which you are entitled.

The study sponsor (those running the trial) will tell you about new information that may affect your health, welfare, or willingness to stay in the study.

 

Ethics Committees

An ethics committee must approve every survey or experiment a psychologist wishes to run.   It is important to obtain ethical approval for each survey to ensure that the questions asked are appropriate and do not cause people offence.   Participants in psychological research should have confidence in the researchers. They should be supplied with all the relevant information about the study, the method of data gathering (e.g. questionnaire, computer test), the sample group (students, children, general public) and the object of the research.   The British Psychological Society has a 'code of conduct' to guide psychologists in their research. The code sets out certain standards which psychologists are required to comply with.   Researchers must consider the ethical implications and psychological consequences for the participants in their research. Threats to their psychological well-being, health, values or dignity should be removed. The researcher should inform all participants of all aspects of the research. The withholding of information or the misleading of participants is unacceptable if the participants are likely to object or show unease once debriefed. Participants should know their right to withdraw from the research at any time. Information obtained about a participant during an investigation is confidential unless otherwise agreed in advance. Researchers have a primary responsibility to protect participants from physical and mental harm during the investigation.   Ethics committees must also be informed of all aspects of the research. They too should be supplied with all the relevant information about the study, the method of data gathering the sample group and the object of the research.   What are ethics committees? Ethics committees review the research and provide advice to ensure the research meets the required ethical standards. The purpose of an ethics committee is to protect the dignity, rights, safety and well being of the individuals involved. Research Ethics Committees (RECs) are independent groups, founded and governed by local Health Authorities or the Department of Health. Research cannot be started until the Research Ethics Committees has given its approval. The Central Office for Research Ethics Committees (COREC) acts on behalf of the Department of Health in England to provide help and leadership for RECs and the REC system by co-ordinating the development of operational and infrastructure arrangements in support of their work. http://www.corec.org.uk/ The Department of Health has created a 'Research Governance Framework for Health and Social Care'. This document provides a framework to ensure research is conducted to high scientific and ethical standards. Follow this link to find out more.   Clinical Trials Research Pharmacist™ The Clinical Trials Research Pharmacist (CTRP™) is a licensed pharmacist who has received his or her Doctor of Pharmacy, and has been trained in providing pharmaceutical care to patients enrolled in clinical trials. The advantages of utilizing this service in clinical trials are tremendous. The initial benefits include increased patient compliance and patient retention. The CTRP™ is able to provide continued positive reinforcement for patients participating in clinical studies through one-on-one contact. This positive reinforcement, coupled with the relationship the patients develop with the CTRP™, helps improve patient satisfaction and will likely impart a positive outlook for participation in future studies. Long-term benefits include improved quality of the data collected, which may improve the statistical power and quicker approval of the study medication. The benefits of utilizing the services of the CTRP™ are accomplished through patient education and monitoring. Study patients need to be informed and knowledgeable about their drug therapies and Informed Consent. Pharmacists have the ability to reinforce and augment such education and compliance in the clinical setting, very much as they currently do in the commercial setting. To date, the role of the pharmacist in providing pharmaceutical care has not been fully utilized in the research setting. We believe that this under utilization of the pharmacist is detrimental to patient care and to the drug approval process. In providing pharmacy counseling services to patients enrolled in clinical trials, we know that study participants are not only more compliant with their medication, but also feel as though they have an advocate with whom they can discuss issues regarding their medication, compliance, and the trial in general. During the trial, the CTRP™ works with clinical investigators, site personnel, and individual study participants to improve drug therapy evaluations, ensure the proper use and administration of study and concomitant medications, and to assist with identifying and documenting adverse events and drug interactions. The patients enrolling in today's clinical trials likely have an understanding and appreciation for the services a pharmacist provides. They may already have a well-established relation with their local pharmacist, and trust them with issues regarding the approved medications they may already be taking. We believe that these patients relate this same trust to the Clinical Trials Research Pharmacist™. With CTRP™, the patients participating in your trial will have access to a Pharm.D. able to answer any and all questions he or she may have regarding their clinical trial medication. The pharmacist will also discuss with the patient the proper use of their study medication, completion of patient diaries, or any medication related issues. Pharmacist intervention has been proven to increase patient compliance, thus improving the success of your trial. CTRP™ pharmacists are there to not only respond to the queries of your patients, but also to proactively contact them. The CTRP™ pharmacist is available 24 hours a day, 7 days a week…on call for your patient! The CTRP™ can provide an array of services based upon the unique needs for each individual trial. In the past, the services provided by the CTRP™ have included: Protocol reviews from a pharmacist and patient consultation perspective Patient and site counseling videos Site training detailing dosing of the study medication Weight-based dosing schedules Telephone consultations with each patient enrolled in the trial IVRS monitoring and follow-up with patients 24/7 availability to the pharmacist   Clinical research in the emergency setting: the role of ethics committees It is important that discussions and decision-making processes be free, open and transparent Probably because of its mixed history of triumph and abuse, medical research has always been regarded with a combination of awe and suspicion. Not surprisingly, research into innovative technologies and dangerous illnesses arouses particular anxieties, and sometimes public controversy. The complexities associated with clinical research in the emergency setting are illustrated by the story recounted in this issue of the Journal of the trial proposed by investigators at Sydney's Royal North Shore Hospital (RNSH) to compare two models of care for patients with acute myocardial infarction (AMI).1 While fibrinolysis has been standard treatment for AMI since the mid-1980s, evidence has suggested that coronary artery angioplasty with stenting produces better outcomes. However, the latter treatment requires advanced technology and skills, limiting its availability. Accordingly, it was proposed to conduct a randomised trial to compare outcomes for patients with AMI of transport to the nearest regional hospital for "conventional" treatment versus transport to RNSH for possible angioplasty.   Two major issues were recognised from the outset: Patients assigned to RNSH would often experience increased transport times to hospital; and It would be difficult to obtain patients' fully informed consent. The first issue is important because delays in initiating treatment after AMI increase the risk of death. The second issue of difficulty obtaining informed consent is encountered in research involving interventions for acute, life-threatening illness, because of shortness of time and the inevitable stress associated with the life-threatening circumstances. Both these issues were taken up by the RNSH ethics committee that meticulously examined the study. After examination of preliminary data, the committee accepted the arguments of the investigators that the benefits of stenting would exceed any increased risk associated with transport delays. It was also decided that it was acceptable to delay provision of detailed information about the trial until the patients arrived at RNSH, even though, in reality, this would often exclude alternatives. Despite complaints provoked by concern within the medical community, approval was eventually granted, but before the trial could begin the Sydney Morning Herald published an article questioning this decision.2 A storm of publicity followed and, months later, the trial has still not commenced. There are several points raised by this case on which there is widespread agreement. In the emergency setting, as elsewhere, rigorous testing is important to identify the most effective treatments and to exclude ineffective, risky or unnecessarily expensive ones. However, the gravity and urgency of the circumstances will often limit the extent to which patients can make carefully considered judgements about whether to participate. Often compromises need to be found. It is the sometimes unenviable job of the responsible ethics committee to attempt to find such a compromise, after considering all the issues and balancing possible risks and benefits. In this case, the scientific questions are well founded and the answers are likely to carry significant implications for medical practice around the world. However, whatever decision is ultimately reached it is unlikely to find acceptance by all protagonists. The complexity of the issues emphasises the importance of the ethics committee process. As with the courts, public confidence in the outcome of ethics committee deliberations depends on a belief that it is fair, free from interference and takes into account all relevant issues. The RNSH ethics committee appears to have acted with propriety and professionalism, but, like other ethics committees, its deliberations are not open to public scrutiny. In addition, it is possible that it did not consider issues affecting other hospitals within the region — for example, the interests of private providers of angioplasty and their patients who could be disadvantaged by the study. The absence of the need to justify decisions in contentious cases, and of a defined appeals process for most committees, creates an appearance of arbitrariness and peremptoriness. The role of the media, which the investigators found so disturbing here, also raises important issues. Medical research is a matter of public interest, and ethics review is not a mere technical function, but a means by which the community ensures that research proposals are adequately evaluated and supervised. Press coverage may be of variable quality, and may itself represent undeclared vested interests. However, as cumbersome and inconvenient as the process may be, if a study has sufficient merit and the review process has been sufficiently robust it is unlikely that public debate and critical reflection will ultimately prevent it from proceeding. This imbroglio provides several important lessons. There are no short cuts to the solution of difficult ethical problems and complete consensus may never be possible. What is most important is that discussions and decision-making processes be free, open and transparent. For these reasons, the tendency for ethics committees to keep their deliberations secret, in the mistaken belief that this is necessary to protect intellectual property, should be reassessed. Promising new models for ensuring public accountability and sharing of experience of committee processes should be examined, such as open access to meetings, chat rooms and the concept of the health ethics archive.3,4 In addition, care must be taken to ensure that current efforts to streamline ethics review processes in the interests of cost and efficiency do not erode the democratic, decentralised nature of the system. In the case of the RNSH trial of treatment for AMI, the investigators should be encouraged to continue dialogue with their interlocutors until the best possible compromise can be reached.

 

Randomized Controlled Trials

Medical research answers many questions about health, illness,
and treatment options. Evaluating new medicines and other treatments
may involve research using randomized controlled trials. In
such trials the participants who receive the treatment under
study are assigned at random (by chance, like the flip of a
coin). This is necessary to ensure that the outcomes are determined
only by the treatment under study and not by other factors that
could otherwise influence treatment assignment. Other participants
who, by the randomization process, serve as controls receive
a standard treatment or placebo treatment (a pill or procedure
that does not include active ingredients). The June 21, 2006,
issue of JAMA includes an article about clinical trials. This
Patient Page is based on one previously published in the November
2, 2005, issue of JAMA.

CLINICAL TRIALS

Clinical trials are designed to answer a specific question about
a treatment, usually the safety and efficacy (how well it works
under optimal conditions) of the treatment. Volunteers who meet
specific criteria, including having the condition being studied,
receive an explanation and, if they choose, join the trial.
This informed consent process should include explaining the
random treatment assignment as well as the risks and possible
benefits of the trial and often includes a written form to document
those issues and the volunteer's consent. In a double-blind
trial, neither the clinicians caring for the patients nor the
participating volunteers know who has been assigned to the active
treatment until the trial is concluded (unless a medical problem
requires that the information be released before that). In a
single-blind trial, the investigators know the treatment assignments
but the participants do not. Blinding procedures protect against
the influence of bias (prejudice) for or against the treatment
being studied.

RESEARCH ETHICS

Before any persons can be enrolled in a clinical trial, the
study must receive approval by an ethics committee (called an
institutional review board in the United States). This is a
panel of individuals, including doctors and community members,
who discuss all of the proposed research studies at a specific
institution (university, medical center, or hospital). The ethics
committee reviews the purpose of the study and its design, the
risks and possible benefits to the participants, and the adequacy
of the informed consent process.

FOR MORE INFORMATION

• National Institutes of Health
  
  http://www.clinicaltrials.gov
  
  http://www.nih.gov
  
  
• National Cancer Institute
  
  800/4-CANCER
  
  http://www.cancer.gov
  
  
• Centers for Disease Control and Prevention
  
  800/311-3435
  http://www.cdc.gov
  
  

INFORM YOURSELF

To find this and previous JAMA Patient Pages, go to the Patient
Page link on JAMA's Web site at http://www.jama.com. A Patient
Page on cancer clinical trials was published in the June 4,
2004, issue; and one on supporting medical research was published
in the September 21, 2005, issue.

Sources: National Cancer Institute, National Institutes of Health,
Centers for Disease Control and Prevention

The JAMA Patient Page is a public service of JAMA. The information
and recommendations appearing on this page are appropriate in
most instances, but they are not a substitute for medical diagnosis.
For specific information concerning your personal medical condition,
JAMA suggests that you consult your physician. This page may
be photocopied noncommercially by physicians and other health
care professionals to share with patients. To purchase bulk
reprints, call 203/259-8724.

TOPIC: MEDICAL RESEARCH

Janet M. Torpy, MD, Writer; Cassio Lynm, MA, Illustrator; Richard M. Glass, MD, Editor

JAMA. 2006;295:2812.

 

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JAMA. 2006;295:2693.
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An Introduction to Clinical Trials

Choosing to participate in a clinical trial is an important personal decision. The following frequently asked questions provide introductory information about clinical trials. In addition, it is often helpful to talk to a physician, family members, or friends about deciding to join a trial. After identifying some trial options, the next step is to contact the study research staff and ask questions about specific trials.

Participation in Clinical Trials

For those considering participation in a clinical trial, the following frequently asked questions are important in understanding the role of the participant and the unique process of clinical trials.

An Introduction to Clinical Trials

Choosing to participate in a clinical trial is an important personal decision. The following frequently asked questions provide detailed information about clinical trials. In addition, it is often helpful to talk to a physician, family members, or friends about deciding to join a trial. After identifying some trial options, the next step is to contact the study research staff and ask questions about specific trials.

What is a clinical trial?

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 a clinical trial?

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 a clinical trial?

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 happens during a clinical trial?

The clinical trial process depends on the kind of trial being conducted (See What are the different types of clinical trials?) The clinical trial team includes doctors and nurses as well as social workers and other health care professionals. They check the health of the participant at the beginning of the trial, give specific instructions for participating in the trial, monitor the participant carefully during the trial, and stay in touch after the trial is completed.

Some clinical trials involve more tests and doctor visits than the participant would normally have for an illness or condition. For all types of trials, the participant works with a research team. Clinical trial participation is most successful when the protocol is carefully followed and there is frequent contact with the research staff.

What is informed consent?

Informed consent is the process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the study to provide information for participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study. If the participant's native language is not English, translation assistance can be provided. Then the research team provides an informed consent document that includes details about the study, such as its purpose, duration, required procedures, and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract, and the participant may withdraw from the trial at any time.

What are the benefits and risks of participating in a clinical trial?

Benefits

Clinical trials that are well-designed and well-executed are the best approach for eligible participants to:

• Play an active role in their own health care.
• Gain access to new research treatments before they are widely available.
• Obtain expert medical care at leading health care facilities during the trial.
• Help others by contributing to medical research.

Risks

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.

What are side effects and adverse reactions?

Side effects are any undesired actions or effects of the experimental drug or treatment. Negative or adverse effects may include headache, nausea, hair loss, skin irritation, or other physical problems. Experimental treatments must be evaluated for both immediate and long-term side effects.

What kind of preparation should a potential participant make for the meeting with the research coordinator or doctor?

• Plan ahead and write down possible questions to ask.
• Ask a friend or relative to come along for support and to hear the responses to the questions.
• Bring a tape recorder to record the discussion to replay later.

Every clinical trial in the U.S. must be approved and monitored by an Institutional Review Board (IRB) to make sure the risks are as low as possible and are worth any potential benefits. An IRB is an independent committee of physicians, statisticians, community advocates, and others that ensures that a clinical trial is ethical and the rights of study participants are protected. All institutions that conduct or support biomedical research involving people must, by federal regulation, have an IRB that initially approves and periodically reviews the research.

Does a participant continue to work with a primary health care provider while in a trial?

Yes. Most clinical trials provide short-term treatments related to a designated illness or condition, but do not provide extended or complete primary health care. In addition, by having the health care provider work with the research team, the participant can ensure that other medications or treatments will not conflict with the protocol.

Can a participant leave a clinical trial after it has begun?

Yes. A participant can leave a clinical trial, at any time. When withdrawing from the trial, the participant should let the research team know about it, and the reasons for leaving the study.

Where do the ideas for trials come from?

Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and in animal studies, the experimental treatments with the most promising laboratory results are moved into clinical trials. During a trial, more and more information is gained about a experimental treatment, its risks and how well it may or may not work.

Who sponsors clinical trials?

Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary groups, and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health (NIH), the Department of Defense (DOD), and the Department of Veteran's Affairs (VA). Trials can take place in a variety of locations, such as hospitals, universities, doctors' offices, or community clinics.

What is a protocol?

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.

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.

What are the phases of clinical trials?

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.

What is an "expanded access" protocol?

Most human use of investigational new drugs takes place in controlled clinical trials conducted to assess safety and efficacy of new drugs. Data from the trials can serve as the basis for the drug marketing application. Sometimes, patients do not qualify for these carefully-controlled trials because of other health problems, age, or other factors. For patients who may benefit from the drug use but don't qualify for the trials, FDA regulations enable manufacturers of investigational new drugs to provide for "expanded access" use of the drug. For example, a treatment IND (Investigational New Drug application) or treatment protocol is a relatively unrestricted study. The primary intent of a treatment IND/protocol is to provide for access to the new drug for people with a life-threatening or serious disease for which there is no good alternative treatment. A secondary purpose for a treatment IND/protocol is to generate additional information about the drug, especially its safety. Expanded access protocols can be undertaken only if clinical investigators are actively studying the experimental treatment in well-controlled studies, or all studies have been completed. There must be evidence that the drug may be an effective treatment in patients like those to be treated under the protocol. The drug cannot expose patients to unreasonable risks given the severity of the disease to be treated.

Some investigational drugs are available from pharmaceutical manufacturers through expanded access programs listed in ClinicalTrials.gov. Expanded access protocols are generally managed by the manufacturer, with the investigational treatment administered by researchers or doctors in office-based practice. If you or a loved one are interested in treatment with an investigational drug under an expanded access protocol listed in ClinicalTrials.gov, review the protocol eligibility criteria and location information and inquire at the Contact Information number.

See "FDA Finds New Ways to Speed Treatments to Patients" for more details. Link to: http://www.fda.gov/fdac/special/newdrug/speeding.html

 

als

 
Assessing the effectiveness of a new drug or new presentation of an established one is an essential part if the development of a medicine. Trials in humans normally involve four phases; assessment in healthy human volunteers, controlled clinical trials in small numbers of patients, large scale safety and efficacy studies prior to registration and controlled post-marketing studies in patients.
Phase I trials are usually undertaken either in 'in house' clinics or in specialist contract facilities using small numbers of healthy volunteers to assess the optimum does and dosage interval. Many parameters are monitored is too monitored (physiological, chemical and pharmacokinetic) as well as possible side effect.
Phase II studies are carried out in small numbers suffering from the condition to be treated. The object of such studies is to assess whether the drug treats the condition to check the dosage in real patients.
Phase III studies assess the safety and effectiveness of a new product in large numbers of patients and are designed to ensure statistical confidence. Trials are undertaken to compare new medicines with both placebo and competing agents. The main objective of these trials is to provide statistically valid safety and efficacy data for registration and market support purposes. Such studies are often undertaken in different centres within a country and in different countries.
Phase IV trials occur after a product has been marketed, when larger numbers of patients may be monitored, both in hospital and in general practice, often to increase knowledge of the safety profit. Smaller scale trials are also used to broaden the company's knowledge of the drug, for example, on aspects such as kinetics in elderly patents, drug interactions and adverse events, comparative efficacy with competing agents and increasingly on cost-benefit.
The preparation and presentation of clinical trial materials must ensure blindness of the test materials and compliance with study protocols. Packaging, labelling and distribution activities must be performed to established good manufacturing practice and good clinical practice standards and must satisfy regulatory requirements. Multinational studies may also need to comply with local regulatory and cultural requirements.

Opportunities

It is easy to make the connection between pharmacy training and employment of a pharmacist in the manufacture and supply of clinical trial materials. However, the pharmacist is also ideally qualified to be a clinical research associate
the pharmacist is also ideally qualified to be a clinical research associate...
involved in the planning, monitoring and reporting of clinical trials. This role involves liaison with scientists and clinicians at all levels with the company and at the clinical trial sites. It also involves frequent travel to the study centres which could be located anywhere in Europe, or the World! A progression from the roles in the clinical trial area can be Quality Assurance, either of the supply process or of the conduct of the clinical trials which gives the pharmacists a chance to use both technical and interpersonal skills to the full.

Cite this: K. T. Shameel, Rahul Soman, "LIGHTENING TOWARDS CLINICAL TRIAL A REVIEW", B. Pharm Projects and Review Articles, Vol. 1, pp. 1635-1679, 2006. (http://farmacists.blogspot.in/)