An adverse drug reaction case report describes one patient's suspected reaction to a medicine and argues how likely it is that the drug caused it. Beyond the CARE items, it names the drug generically, dates every exposure against the reaction, reports dechallenge and rechallenge, assesses causality with a named tool and cites the regulatory report.
CARE still sets the structure, and consent for publication is still required: see how to write a case report using the CARE checklist and patient consent for case reports. The two causality tools covered here are the Naranjo scale and the system of the World Health Organization (WHO) and the Uppsala Monitoring Centre (UMC), known as WHO-UMC.
What an adverse drug reaction case report adds to CARE
The CARE checklist already asks for each intervention's dosage, strength and duration, and for adverse and unanticipated events. The drug-specific items come from the 2007 Guidelines for submitting adverse event reports for publication, listed by the EQUATOR Network. Two societies endorse it: the International Society of Pharmacovigilance (ISoP) and the International Society for Pharmacoepidemiology (ISPE). ISPE hosts a free full text of the guideline, whose table marks each item Required, Highly desirable or If relevant.
| What to report | Column in the 2007 guideline | Where to put it |
|---|---|---|
| The suspected drug, by its generic name | Required | Case presentation, at first mention |
| The brand name, with strength and dosage unit | Highly desirable | Case presentation, once |
| Presence or absence of evidence for a causal link, including timing, dechallenge and rechallenge, or why these were not possible | Required | Discussion |
| Earlier reports of the reaction in journals and in the product labelling | Required | Discussion |
| Competing explanations and biological plausibility | Highly desirable | Discussion |
| Earlier reports of the reaction to regulatory agencies | Highly desirable | Discussion |
If a recommended item is missing, the guideline asks you to say whether it was unavailable or available but not reported.
Build the exposure timeline in days, with every medicine on it
A causality argument rests on sequence, so the timeline carries the report. Set day 0 as the first dose of the suspected drug and count every other event from it. Relative days also keep calendar dates, which can help identify a patient, out of the paper. List every medicine taken in the period, including non-prescription and herbal products, with each start, change, stop and restart.
The case below is invented to illustrate the structure; its details are not real data. A real report adds each medicine's dose, route and formulation, omitted here because this guide gives no dosing information.
| Day | What happened | Suspected drug (Drug A) | Other medicines |
|---|---|---|---|
| Before day 0 | Long-standing condition treated with Drug B for over a year | Not taken | Drug B, unchanged |
| Day 0 | Drug A started for a new condition | Started | Drug B |
| Day 9 | Itchy widespread rash; no new medicines, foods or skin products; no signs of infection | Taken | Drug B |
| Day 10 | Drug A stopped | Stopped (dechallenge) | Drug B |
| Day 11 | Reaction reported to the national scheme; report number recorded | Not taken | Drug B |
| Day 16 | Rash resolved | Not restarted | Drug B |
| Day 70 | Follow-up: no recurrence | Not restarted (no rechallenge) | Drug B |
Three intervals belong in the text: onset 9 days after Drug A was started, withdrawal 1 day after onset, and resolution 6 days after withdrawal. Drug B had been taken unchanged for over a year before the rash, which argues against it without excluding it.
Report dechallenge and rechallenge, or say why there was none
Dechallenge means withdrawing the suspected drug to see whether the reaction continues; rechallenge means giving it again after it was stopped. The Council for International Organizations of Medical Sciences (CIOMS) defines both in its pharmacovigilance glossary, and the 2007 guideline makes reporting them, or why they were not possible, a Required item.
| Term | What happened | What the report should say |
|---|---|---|
| Positive dechallenge | Reaction lessened or disappeared | When it improved, and any treatment given for it at the same time |
| Negative dechallenge | Reaction continued | How long you observed, and what else might sustain it |
| Partial dechallenge | Dose reduced, not stopped | That the drug was only reduced |
| Positive rechallenge | Reaction reappeared when the drug was given again | The full sequence: stopped, improved, restarted, reappeared |
| Negative rechallenge | Reaction did not reappear | That this suggests, but does not prove, no causal link |
A later exposure counts as a rechallenge only if the drug had been stopped first. Do not restart a drug to strengthen a paper. CIOMS, quoting its Working Group V report, says a deliberate rechallenge should happen only when the treating physician judges the expected result directly relevant to the patient's treatment and well-being. The WHO-UMC document adds that rechallenge is rarely ethically justified. When there was none, say so and give the reason.
Assess causality with Naranjo or WHO-UMC, and show the working
| Feature | Naranjo scale | WHO-UMC system |
|---|---|---|
| Source | Clinical Pharmacology and Therapeutics, 1981 | WHO document dated June 2013 |
| Method | 10 questions, each answered Yes, No or Do not know, scoring -1, 0, +1 or +2 | Six categories, each with criteria that should all be reasonably met; no points |
| Result | A total from -4 to +13 | One category |
| Categories | Definite (9 or more), probable (5 to 8), possible (1 to 4), doubtful (0 or less) | Certain; Probable/Likely; Possible; Unlikely; Conditional/Unclassified; Unassessable/Unclassifiable |
| Rechallenge | Per LiverTox, scores +2 only if the drug was stopped, the reaction resolved or improved, and it clearly returned or worsened on restarting at a similar dose by the same route | Not required for Probable/Likely; even a positive one cannot make an event Certain unless it is pharmacologically or phenomenologically definitive |
Name the tool and give its result in that tool's own words: a Naranjo total of 6 is probable, not likely, and WHO-UMC has no definite category. Show the working by listing each Naranjo question with its answer and score. Use the wording on the Naranjo scale page of LiverTox, a US National Institutes of Health resource on drug-induced liver injury. When more than one drug is suspected, LiverTox advises scoring each separately and considering an interaction.
Write out the alternatives, too. WHO-UMC's Probable/Likely category requires an event unlikely to be attributed to disease or other drugs. A reader can check that only if you list each alternative with the evidence against it.
Causality was assessed by [roles of the assessors] using [the Naranjo scale / the WHO-UMC system]. The reaction began [n] days after [generic drug name] was started. The drug was [stopped / reduced] on day [n], and the reaction [resolved / improved / persisted] by day [n]. [Any treatment given for the reaction.]
The drug was not restarted, because [reason]. Or: it was restarted on day [n] for [clinical reason], and the reaction [recurred / did not recur].
Alternative explanations considered were [list], each judged unlikely because [evidence]. The Naranjo total was [score] ([band]), with each answer in [table]. Or: the WHO-UMC category was [category]. The reaction was reported to [scheme], report number [number].
Report the reaction to your medicines regulator and cite the number
The 2007 guideline says authors should have reported the case to the appropriate regulatory authority and, if possible, give the report number so duplicates can be identified.
| Where the reaction occurred | Reporting route |
|---|---|
| United States | MedWatch, run by the US Food and Drug Administration (FDA), open to health professionals, patients and consumers |
| United Kingdom | Yellow Card, run by the Medicines and Healthcare products Regulatory Agency (MHRA), open to anyone |
| European Economic Area | Your national medicines regulator; the European Medicines Agency operates EudraVigilance |
| Elsewhere | Your national pharmacovigilance centre or medicines regulator |
If your Discussion quotes counts from VigiBase, the WHO global database of adverse event reports that UMC maintains, give the date of each count and do not present them as a frequency. The UMC caveat document says VigiBase holds no information on how many people were exposed. A disproportionality analysis of such a database is a different paper, with its own reporting guideline.
Word the conclusion as a signal, not as proof
Causality tools classify likelihood; they do not prove cause, and the WHO-UMC document says so. The FDA's non-binding 2005 pharmacovigilance guidance says even a single well-documented case report can be a signal, particularly one with a positive rechallenge. It adds that a signal may or may not lead to the conclusion that the product caused the event.
| Wording that overclaims | Wording one case supports |
|---|---|
| Drug A causes rash. | A rash began 9 days after Drug A was started and resolved 6 days after it was stopped; causality was assessed as Probable/Likely under WHO-UMC. |
| This confirms the association. | This case adds to [n] previously published reports found by the search described above. |
| The first reported case of this reaction. | A dated search statement naming the databases searched. |
| A severe reaction, so clearly drug-related. | Severity and causality, reported separately. |
A novelty claim is a statement about your search: see how to search before calling a case the first reported. For why a severity grade says nothing about cause, see RECIST and CTCAE reporting. Carry the generic name, latency, dechallenge result and causality category into the abstract, using how to write a case report abstract.
A pre-submission checklist for a drug-reaction case report
- Suspected drug named generically; any brand name given once.
- Every medicine listed with its start, change, stop and restart days.
- Day 0 defined; onset, withdrawal and resolution intervals stated.
- Dechallenge result given: stopped or only reduced, and any treatment of the reaction.
- Rechallenge reported with its full sequence, or its absence explained.
- Alternative explanations listed with the evidence against each.
- Earlier reports in journals and in the product labelling discussed.
- Causality tool named, result in its own terms, working shown.
- Regulator report made; number quoted where available.
- No database count presented as a frequency.
- Missing items explained as unavailable or not reported.
- CARE checklist complete; consent for publication stated.
Our author guidelines ask you to match the manuscript to the relevant EQUATOR checklist. For a suspected drug reaction, EQUATOR lists CARE for case reports and the 2007 guideline for adverse event reports; use them together. If you spot an error in this guide, see how to report a problem to us.