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What is Dechallenge, Rechallenge and Prechallenge in Clinical trials?

“Challenge – Challenge refers to the giving of the drug to the patient during the AE or treatment in question. 

That is, a patient is started today on, say, ampicillin orally.  This is the “challenge”.

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Dechallenge (DC) and Rechallenge (RC) terminology often used in clinical trial to determine action taken for medical product.

It specifically refers to suspect drug but not for event as whole.

Dechallenge : 

Dechallenge : This term is use when the suspect drug was discontinued or withdrawn or dose reduced due to adverse event (AE).

Dechallenge (DC) can be classified into

  1. Positive Dechallenge: When the suspect drug was stopped or withdrawn, or the dose was reduced, and the adverse event was improved or resolved.

For example, the AE (which could actually be an adverse reaction – AR) of diarrhoea went away a day after the patient stopped taking ampicillin.

  • Negative Dechallenge: When the suspect drug was discontinued or withdrawn, or the dose was reduced, but the adverse event did not improve or resolve. For instance, the diarrhoea persisted even after the ampicillin was discontinued.

It’s important to note that these can be a little confusing because a “positive” dechallenge refers to the problem disappearing.

  • Unknown: When suspect drug was discontinued or withdrawn or dose reduced but the result of dechallange was unknown.
  • Dechallenge not applicable: This term is used in the following situations: treatment for an adverse event, death, drug discontinuation prior to the AE, medication error, drug overdose, and drug exposure during pregnancy.

Rechallenge (RC):

Rechallenge (RC): This term is use when the suspect drug wasrestarted after dechallenge and it only applicable after positive dechallenge.

Rechallenge (RC) can be classified into:

  1. Positive Rechallenge: When the suspect drug was re-introduced and event reappeared.
  2. Negative Rechallenge: when the suspect drug re-introduced and event did not reappear.
  3. Unknown: when the suspect drug re-introduced but result of rechallange was unknown.
  4. Rechallenge not applicable: when the drug was not re-introduced.


Prechallenge: This is a relatively new term that refers to the use of the same drug in the past. For example, the patient may have taken Ampicillin for an infection two years ago. If the patient previously took the drug and no adverse events occurred, this argues against the drug causing the AE in the current instance.

Moreover, this has a number of flaws, including forgetting what happened if it happened years ago.

In the case of an allergic reaction, the first use “primes the pump,” so to speak, and the allergic reaction manifests itself only on subsequent uses. This is a flimsy concept.

So, the general principles around these concepts run as follows:

If a patient takes a drug and experiences an adverse effect (AE), the question is whether the AE is due to the drug (thus an AR or Adverse Drug Reaction ADR) or not.

Obviously, this is a critical point in determining the drug’s safety and whether or not it can or should be continued in the specific patient.

As the FDA has stated, it is typically difficult to determine causality in a single individual experiencing an AE.

However, we must do so in clinical trials as well as in post-marketing signalling cases. After the AE occurs, it is common for the physician to discontinue the drug to see if the AE resolves.

If it does disappear, this is a positive dechallenge and suggests that, at least in terms of the temporal aspects of the case, the drug may be the source of the AE.

If it does not disappear, it may be less likely that drug was the cause of the event, unless the drug caused an irreversible change that cannot be reversed (e.g. blindness).

If the AE disappears and the patient really needs the drug and there are no adequate substitutes, the doctor may consider restarting drug if the AE was not serious or severe (one would avoid restarting if the AE was, say, laryngospasm or ventricular tachycardia).

This is the rechallenge.

If the drug is used again and the same AE occurs, this is considered a positive rechallenge and is regarded by many as a fairly strong indicator of causality: the drug is a likely suspect cause of the AE.

If the AE does not reoccur, many people believe that the drug did not cause it, and causality is less likely.

Finally, a second dechallenge is possible. The same scenario as before.”





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