Challenge–dechallenge–rechallenge (CDR) is a medical testing protocol in which a medicine or drug is administered, withdrawn, then re-administered, while being monitored for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 An adverse effect is an undesired harmful 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. The term compl ...

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 dechallenge (withdrawal) 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 reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...

s. The

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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.

Fluoxetine and suicide

Peter Breggin asserted that there was an association between

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...

(Prozac) use and

suicidal thoughts Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...

. 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 suicidality, statistical testing was considered inappropriate. Other researchers have similarly suggested that the CDR is useful for researching the

adverse effect An adverse effect is an undesired harmful effect resulting from a Pharmaceutical drug, medication or other Surgery#Definitions, intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main ...

of suicidality while taking fluoxetine, and

Eli Lilly Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...

adopted the protocol rather than

randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...

s when testing for increased risk of suicide. In addition to suicidality,

akathisia Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back a ...

is a reaction to medication which is suggested as amenable to a CDR protocol.

Clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s using a CDR protocol are also reported for clinicians attempting to assess the effects of a medication on patients.

References

{{DEFAULTSORT:Challenge-dechallenge-rechallenge Design of experiments Medical tests

Use in drug testing

Fluoxetine and suicide

See also

References