CBC News Online |
A large and growing industry has sprung up around clinical
trials. When the lab mice have done their bit, when the computers have crunched
the data, when the last test tube has been emptied the only way to be
reasonably sure a new drug works safely in people is to have humans try it.
Every year, thousands of Canadians volunteer to be human guinea pigs by
participating in clinical trials. The vast majority pass through the process
unscathed, but in rare cases a trial can go wrong, with serious consequences.
Clinical trials are studies conducted on humans and their
interaction with new drugs, treatments and vaccines. The trials are carefully
crafted to answer specific questions about the effectiveness of new therapies,
or to find out more about specific diseases and ailments.
QUICK FACT
Montreal has the largest number of clinical trial
organizations of any city in North America. With large pharmaceutical companies
scrambling to be the first to market with the latest concoction to cure or treat
society's ills and pains, it's no surprise that new, experimental drugs have
quickly become the mainstay of the clinical trial industry.
Before a company can put a new drug on the shelves, it is
required to conduct a roster of studies to ensure the medication is safe and
effective for patients. The results of those studies are then handed over to
Health Canada as part of the company's application to have the drug approved for
sale.
And while the pushing of pills is inarguably big business for big pharma, a
large and growing industry has also sprung up around clinical trials.
Just a couple of decades ago, most drug trials were publicly funded. Now,
companies that conduct drug studies are popping up, paid by pharma giants to
conduct the studies and help navigate the regulatory process.
According to Industry Canada, spending on research and development by the
biopharmaceutical industry, estimated at $33 billion worldwide in 2001, is
growing by 15 per cent per year. Approximately 40 per cent of that goes towards
clinical trials.
Of that, an estimated $1.3 billion is spent per year on recruitment for the
trials ($1 billion on patient and $300 million on physician recruitment.)
All told, the cost of developing and launching a new drug is estimated to be
between $659 million and $800 million US.
If you're interested in participating in a clinical trial, your first stop is
your doctor's office. Talk with your doctor about the treatments you're
interested in. Ask your doctor whether he or she has a list of scientifically
sound and ethical trials currently taking place in your city.
There are both benefits and risks associated with clinical trials. By
participating in a clinical trial, you can:
Take an active role in your own health care.
Possibly gain access to new treatments that are not available to the public. This may be especially useful if you have not responded well to existing treatments.
Obtain expert medical care at leading health care facilities during the trial. Typically, a volunteer in a clinical trial receives more medical attention, more lab tests, and will be closely monitored by researchers, who are often leading specialists in their field.
Help others by helping to further medical research.
Clinical trials also have risks:
There may be unintended and possibly dangerous adverse reactions and side effects to medications or treatments.
The new drug/treatment may not be any more effective than the previous drug/treatment.
The protocol may require a lot of your time for trips to the study site, treatments, hospital stays, or complex dosage requirements.
You may be placed in the "control group," meaning that instead of receiving the new drug, you may get a placebo.
Do your own
research
After discussing the matter with your doctor, if you're still interested in
participating in a particular trial you'll need to meet with the doctor or nurse
managing the trial for a screening interview.
You should know as much as possible about the research study before you meet
with the trial representative. You should feel comfortable asking questions and
the staff should answer them in a way you can understand.
Plan ahead and write down the questions you want to ask.
Ask a friend or relative to come with you for support and to hear the responses to your questions.
Take notes, or bring a tape recorder so you can replay the discussion after you get home.
Some questions you might ask about the research include:
Why is this research being done?
What is the purpose of the study?
Who is sponsoring/paying for the trial?
Who has reviewed and approved this study?
Why does the research team think the treatment, drug, or medical device will work?
Some questions about your participation in the study include:
Where is the trial being conducted?
What kinds of therapies, procedures, and/or tests will I have during the trial?
Will they hurt? If so, for how long?
How will the tests in the study compare to tests I would have outside the study?
How long will the trial last?
How often will I have to go to the study site?
Who will provide my medical care after the study ends?
Will I be able to take my regular medications during the trial?
What medications, procedures, or treatments must I avoid while in the study?
What are my responsibilities during the study?
Will I have to be in the hospital during the study?
Will the study researchers work with my doctor while I am in the study?
Can anyone find out that I am participating in a study?
Can I talk to other people in the study?
Will I be able to find out the results of the trial?
Can I opt to remain on this treatment,
even after termination of the trial?
Questions about risks and benefits include:
How do the possible risks and benefits of the study compare with approved treatments for me?
What are the possible immediate and long-term side effects?
How will patient safety be monitored?
What happens if I am harmed by the trial?
Other questions include:
What are the alternative treatments besides the one being tested in the trial?
Will I have to pay anything to participate in the study?
What are the charges likely to be?
Is my insurance likely to cover those expenses?
How much does a trial pay?
Some clinical trials will pay you for
participating, while others will not. In some programs, researchers will
reimburse you for expenses associated with participating in the research. Such
expenses may include transportation costs, childcare, meals and accommodations.
Other points to consider:
Drug companies hire for-profit companies to find patients and conduct the study
on time and on budget. Physicians are increasingly being offered payment for
enrolling patients in clinical trials. This creates a conflict; a physician's
role should be to advise their patients about what is in their best interest
without regard for personal profit. To speed up the approval process, drug
companies often employ for-profit ethical review committees rather than
volunteer committees that have no vested interest in the study.
Never feel pressured into joining a clinical trial. If your questions are not
fully answered by the research nurse or doctor at the outset, discuss the
benefits and risks of participating with your family doctor before signing a
consent form.
If you have any concerns during the trial, contact the clinician in charge or
the head of the institution's ethics committee that approved the trial. (You
should have been given the committee's telephone number). If the ethical
approval was by a for-profit company, seek advice from your family physician as
to whether it's advisable to continue in the trial.
You can withdraw from the study at any time for whatever reason. If you plan to
stop participating, you might let the research team know why you are leaving the
study, although you are not required to explain your decision for withdrawing to
anyone.
[Sources: CBC News: Marketplace, Health Canada, myhealthCANADA, U.S. National
Institute of Allergy and Infectious Diseases, Medbroadcast]
Adverse Drug Reaction (ADR)
An unintended reaction to a drug taken at doses normally used in
humans for prophylaxis, diagnosis, or therapy of disease, or for the
modification of physiological function. In clinical trials, an ADR would include
any injuries by overdosing, abuse/dependence, and unintended interactions with
other medicinal products.
Adverse Event (AE)
A negative experience encountered by an individual during the course
of a clinical trial, that is associated with the drug. An AE can include
previously undetected symptoms, or the exacerbation of a pre-existing condition.
When an AE has been determined to be related to the product on trial, it is
considered an Adverse Drug Reaction.
Adverse Event Reports
Investigator reports of all serious and adverse events, injury and
deaths given to the sponsor, the REB and Health Canada.
Biologic
A virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood
component or derivative, allergenic product, or analogous product applicable to
the prevention, treatment or cure of diseases or injuries of humans.
Biotechnology
Any technique that uses living organisms, or substances from
organisms, biological systems, or processes to make or modify a product or
process, to change plants or animals, or to develop micro-organisms for specific
uses.
Blinding
The process through which one or more parties to a clinical trial are
unaware of the treatment assignments. In a single-blinded study, usually the
subjects are unaware of the treatment assignments. In a double-blinded study,
both the subjects and the investigators are unaware of the treatment
assignments. Also, in a double-blinded study, the monitors and sometimes the
data analysts are unaware. "Blinded" studies are conducted to prevent the
unintentional biases that can affect subject data when treatment assignments are
known.
Clinical Investigation
A systematic study designed to evaluate a product (drug, device, or
biologic) using human subjects, in the treatment, prevention, or diagnosis of a
disease or condition, as determined by the product's benefits relative to its
risks. Clinical investigations can only be conducted with the approval of Health
Canada.
Clinical Research
Study of drug, biologic or device in human subjects with the intent
to discover potential beneficial effects and/or determine its safety and
efficacy. Also called clinical study and clinical investigation. It does not
encompass all the research that is carried out in the clinical setting (e.g.,
health services research).
Clinical Study Materials
Study supplies (i.e., study test article, laboratory supplies, case
report forms) provided by the study sponsor to the investigator.
Clinical Trial
Any investigation in human subjects intended to determine the
clinical pharmacological, pharmacokinetic, and/or other pharmacodynamic effects
of an investigational agent, and/or to identify any adverse reactions to an
investigational agent to assess the agent's safety and efficacy.
Consent Form
A document explaining all relevant study information to assist the
study volunteer in understanding the expectations and requirements of
participation in a clinical trial. This document is presented to and signed by
the study subject.
Contract Research Organization (CRO)
A person or an organization (commercial, academic or other)
contracted by the sponsor to perform one or more of a sponsor's study-related
duties and functions.
Control Group
A comparison group of study subjects who are not treated with the
investigational agent. The subjects in this group may receive no therapy, a
different therapy, or a placebo.
Data
This term is legally defined according to the institution. It
generally refers to recorded information regardless of form. Most institutions
hold title to data while researchers have rights to access the data.
Data Management
The process of handling the data gathered during a clinical trial.
May also refer to the department responsible for managing data entry and
database generation and/or maintenance.
Deception
Intentionally misleading or withholding information about the nature
of an experiment.
Declaration of Helsinki
A series of guidelines adopted by the 18th World Medical Assembly in
Helsinki, Finland, in 1964. The declaration addresses ethical issues for
physicians conducting biomedical research involving human subjects.
Recommendations include the procedures required to ensure subject safety in
clinical trials, including informed consent and ethics committee reviews.
Demographic Data
Refers to the characteristics of study participants, including sex,
age, family medical history, and other characteristics relevant to the study in
which they are enrolled.
Device
An instrument, apparatus, implement, machine, contrivance, implant,
in vitro reagent, or other similar or related article, including any component,
part or accessory, which is intended for use in the diagnosis, cure, treatment
or prevention of disease. A device does not achieve its intended purpose through
chemical action in the body and is not dependent upon being metabolized to
achieve its purpose.
Documentation
All forms of records that describe or document study methods, conduct
and results, including any adverse events and actions taken.
Double blind
The design of a study in which neither the investigator or the
subject knows which medication (or placebo) the subject is receiving.
Drug
As defined by the Food and Drugs Act, a drug "includes any substance
or mixture of substances manufactured, sold or represented for use in a) the
diagnosis, treatment, mitigation or prevention of a disease, disorder or
abnormal physical state, or its symptoms, in human beings or animals, b)
restoring, correcting or modifying organic functions in human beings or animals,
or c) disinfection in premises in which food is manufactured, prepared or kept."
Drug product
A finished dosage form (e.g. tablet, capsule, or solution) that
contains the active drug ingredient usually combined with inactive ingredients.
Effective dose
The dose of an investigational agent that produces the outcome
considered "effective," as defined in the study protocol. This could mean a cure
of the disease in question or simply the mitigation of symptoms.
Efficacy
A product's ability to produce beneficial effects on the duration or
course of a disease. Efficacy is measured by evaluating the clinical and
statistical results of clinical tests.
Ethics committee
An independent group of both medical and non-medical professionals
who are responsible for verifying the integrity of a study and ensuring the
safety, integrity, and human rights of the study participants.
Exclusion criteria
Refers to the characteristics that would prevent a subject from
participating in a clinical trial, as outlined in the study protocol.
Food and Drug Administration (FDA)
The U.S. Department of Health and Human Services agency that enforces
the U.S. Food, Drug and Cosmetics Act and related federal public health laws,
and grants investigational and new drug approvals.
Formulation
The mixture of chemicals and/or biological substances and excipients
used to prepare dosage forms.
Generic drug
A medicinal product with the same active ingredient, but not
necessarily the same inactive ingredients as a brand-name drug. A generic drug
may only be marketed after the original drug's patent has expired.
Good clinical practice (GCP)
International ethical and scientific quality standard for designing,
conducting, monitoring, recording, auditing, analyzing and reporting studies.
Insures that the data reported is credible and accurate, and that the subject's
rights and confidentiality are protected.
Human subject
A patient or healthy individual participating in a research study. A
living individual about whom an investigator obtains private information or data
through intervention or interaction.
Inclusion criteria
A list of criteria that must be met by all study subjects.
Informed consent
The voluntary verification of a patient's willingness to participate
in a clinical trial, along with the documentation thereof. This verification is
requested only after complete, objective information has been given about the
trial, including an explanation of the study's objectives, potential benefits,
risks and inconveniences, alternative therapies available, and of the subject's
rights and responsibilities in accordance with the current revision of the
Declaration of Helsinki.
Institution
Location of research. Retains ultimate responsibility for human
subject regulation compliance.
Investigator
A medical professional, usually a physician but may also be a nurse,
pharmacist or other health-care professional, under whose direction an
investigational drug is administered or dispensed. A principal investigator is
responsible for the overall conduct of the clinical trial at his/her site.
Investigator's brochure
Relevant clinical and non-clinical data compiled on the
investigational drug, biologic or device being studied.
In vitro testing
Non-clinical testing conducted in an artificial environment such as a
test tube or culture medium.
In vivo testing
Testing conducted in living animal and human systems.
Longitudinal study
A study conducted over a long period of time.
Monitor
Person employed by the sponsor or CRO who reviews study records to
determine that a study is being conducted in accordance with the protocol. A
monitor's duties may include, but are not limited to, helping to plan and
initiate a study, and assessing the conduct of studies. Monitors work with the
clinical research co-ordinator to check all data and documentation from the
study. See also CRA.
Monitoring
Reviewing a clinical study, ensuring conduct, proper records and
reports are performed as stated in the clinical protocol, standard operating
procedures, GCP and by regulatory requirements.
Nuremberg code
As a result of the medical experimentation conducted by Nazis during
the Second World War, the U.S. Military Tribunal in Nuremberg in 1947 set forth
a code of medical ethics for researchers conducting clinical trials. The code is
designed to protect the safety and integrity of study participants.
Off label
The use of a drug for a purpose other than that approved of by Health
Canada.
Open-label study
A study in which all parties, (patient, physician and study
coordinator) are informed of the drug and dose being administered. In an
open-label study, none of the participants are given placebos. These are usually
conducted with Phase I & II studies.
Over the counter (OTC)
Drugs available for purchase without a physician's prescription.
Patient
Individual seeking medical care.
Pharmacoeconomics
The study of cost-benefit ratios of drugs with other therapies
or with similar drugs. Pharmacoeconomic studies compare various treatment
options in terms of their cost, both financial and quality of life. Also
referred to as "outcomes research."
Phase I study
The first of four phases of clinical trials, Phase I studies are designed to
establish the effects of a new drug in humans. These studies are usually
conducted on small populations of healthy humans to specifically determine a
drug's toxicity, absorption, distribution and metabolism.
Phase II study
After the successful completion of phase I trials, a drug is then tested for
safety and efficacy in a slightly larger population of individuals who are
afflicted with the disease or condition for which the drug was developed.
Phase III study
The third and last pre-approval round of testing of a drug is
conducted on large populations of afflicted patients. Phase III studies usually
test the new drug in comparison with the standard therapy currently being used
for the disease in question. The results of these trials usually provide the
information that is included in the package insert and labeling.
Phase IV study
After a drug has been approved by Health Canada, phase IV studies are
conducted to compare the drug to a competitor, explore additional patient
populations, or to further study any adverse events.
Pivotal study
Usually a phase III study which presents the data that Health Canada
uses to decide whether or not to approve a drug. A pivotal study will generally
be well-controlled, randomized, of adequate size, and whenever possible, double
blind.
Placebo
An inactive substance designed to resemble the drug being tested. It
is used as a control to rule out any psychological effects testing may present.
Most well-designed studies include a control group which is unwittingly taking a
placebo.
Pre-clinical testing
Before a drug may be tested on humans, pre-clinical studies must be
conducted either in vitro but usually in vivo on animals to determine that the
drug is safe.
Protocol
A detailed plan that sets forth the objectives, study design, and
methodology for a clinical trial. A study protocol must be approved by an REB
before investigational drugs may be administered to humans.
Protocol amendment
Changes or clarifications made in writing to the original protocol.
Quality assurance
Systems and procedures designed to ensure that a study is being
performed in compliance with Good Clinical Practice (GCP) guidelines and that
the data being generated is accurate.
Randomization
Study participants are usually assigned to groups in such a way that
each participant has an equal chance of being assigned to each treatment (or
control) group. Since randomization ensures that no specific criteria are used
to assign any patients to a particular group, all the groups will be equally
comparable.
Recruitment
Act of enrolling subjects with the proper inclusion criteria.
Recruitment period
Time allowed to recruit all subjects for a study.
Regulatory affairs
In clinical trials, the department or function that is responsible
for ensuring compliance with government regulations and interacts with the
regulatory agencies. Each drug sponsor has a regulatory affairs department that
manages the entire drug approval process.
Research
Systematic investigation designed to develop or contribute to
generalizable knowledge. Includes Clinical Research.
Review Ethics Board (REB)
An independent group of professionals designated to review and
approve the clinical protocol, informed consent forms, study advertisements, and
patient brochures, to ensure that the study is safe and effective for human
participation. It is also the REB's responsibility to ensure that the study
adheres to Health Canada's regulations.
Research team
Investigator, sub-investigator and clinical research co-ordinator
involved with study.
Risk benefit ratio
Risk to individual subject vs. potential benefits. Also called
Risk-Benefit Analysis.
Serious adverse event (SAE)
Any adverse event (AE) that is fatal, life-threatening, permanently
disabling, or which results in hospitalization, initial or prolonged.
Source data
All information contained in original records and certified copies of
results, observations or other facets required for the reconstruction and
evaluation of the study that is contained in source documents.
Source documentation
Location where information is first recorded including original
documents, data and records.
Sponsor
Individual, company, institution or organization taking
responsibility for initiation, management and financing of study.
Standard operating procedure (SOP)
Official, detailed, written instructions for the management of
clinical trials. SOPs ensure that all the functions and activities of a clinical
trial are carried out in a consistent and efficient manner.
Standard treatment
The currently accepted treatment or intervention considered to be
effective in the treatment of a specific disease or condition.
Sub-investigator
Helps design and conduct investigation at a study site.
Subject/study subject
Participant in a study. See "Human Subject."
Telephone report
Notification via telephone to Health Canada of unexpected fatal or
life threatening advent associated with a clinical study.
Unexpected adverse drug reaction
A reaction that is not consistent in nature or severity with study
application.
Vulnerable subjects
Group/individual that cannot give informed consent because of limited
autonomy (e.g., children, mentally ill and prisoners). Also refers to subjects
who may be unduly influenced to participate (e.g., students, subordinates and
patients).
Well being
Subject's physical and mental soundness.
He who slings mud generally loses ground. Adlai Stevenson
MGM
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