Challenge-dechallenge-rechallenge
Encyclopedia
Challenge-dechallenge-rechallenge (CDR) is a medical testing protocol
in which a medicine
or drug
is administered, withdrawn, then re-administered, while being monitored for adverse effects
at each stage. The protocol is used when statistical testing
is inappropriate due to an idiosyncratic reaction by a specific individual, or a lack of sufficient test subjects and unit of analysis is the individual. During the withdraw phase, the medication is allowed to wash out of the system in order to determine what effect the medication is having on an individual.
s. The Food and Drug Administration
of the United States
lists positive dechallenge reactions (an adverse event which disappears on withdrawal of the medication) as well as negative (an adverse event which continues after withdrawal), as well as positive rechallenge (symptoms re-occurring on re-administration) and negative rechallenge (failure of a symptom to re-occur after re-administration). It is one of the standard means of assessing adverse drug reactions in France
.
asserted that there was an association between fluoxetine
(Prozac) use and suicidal ideation
. While his research group were investigating the effectiveness and side effects of the medication, Breggin noticed that only certain individuals responded to the medication with increased thoughts of suicide
, and used the challenge-dechallenge-rechallenge protocol in an effort to verify the link. Given the low occurrence rate of sucidality, statistical testing was considered inappropriate. Other researchers have similarly suggested that the CDR is useful for researching the adverse effect
of suicidality while taking fluoxetine, and Eli Lilly
adopted the protocol rather than randomized controlled trial
s when testing for increased risk of suicide. In addition to suicidality, akathisia
is a reaction to medication which is suggested as amendable to a CDR protocol.
Clinical trial
s using a CDR protocol are also reported for clinicians attempting to assess the effects of a medication on patients.
Protocol (natural sciences)
In the natural sciences a protocol is a predefined written procedural method in the design and implementation of experiments. Protocols are written whenever it is desirable to standardize a laboratory method to ensure successful replication of results by others in the same laboratory or by other...
in which a medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
or drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
is administered, withdrawn, then re-administered, while being monitored for adverse effects
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
at each stage. The protocol is used when statistical testing
Statistics
Statistics is the study of the collection, organization, analysis, and interpretation of data. It deals with all aspects of this, including the planning of data collection in terms of the design of surveys and experiments....
is inappropriate due to an idiosyncratic reaction by a specific individual, or a lack of sufficient test subjects and unit of analysis is the individual. During the withdraw phase, the medication is allowed to wash out of the system in order to determine what effect the medication is having on an individual.
Use in drug testing
CDR is one means of establishing the validity and benefits of medication in treating specific conditions as well as any adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s. The Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
of the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
lists positive dechallenge reactions (an adverse event which disappears on withdrawal of the medication) as well as negative (an adverse event which continues after withdrawal), as well as positive rechallenge (symptoms re-occurring on re-administration) and negative rechallenge (failure of a symptom to re-occur after re-administration). It is one of the standard means of assessing adverse drug reactions in France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
.
Fluoxetine and suicide
Peter BregginPeter Breggin
Peter Roger Breggin is an American psychiatrist and critic of biological psychiatry and psychiatric medication. In his books, he advocates replacing psychiatry's use of drugs and electroconvulsive therapy with humanistic approaches, such as psychotherapy, education, and broader human...
asserted that there was an association between fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
(Prozac) use and suicidal ideation
Suicidal ideation
Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts...
. While his research group were investigating the effectiveness and side effects of the medication, Breggin noticed that only certain individuals responded to the medication with increased thoughts of suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
, and used the challenge-dechallenge-rechallenge protocol in an effort to verify the link. Given the low occurrence rate of sucidality, statistical testing was considered inappropriate. Other researchers have similarly suggested that the CDR is useful for researching the adverse effect
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
of suicidality while taking fluoxetine, and Eli Lilly
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
adopted the protocol rather than randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s when testing for increased risk of suicide. In addition to suicidality, akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
is a reaction to medication which is suggested as amendable to a CDR protocol.
Clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s using a CDR protocol are also reported for clinicians attempting to assess the effects of a medication on patients.