Brief · Use case · Pharmacovigilance

Drug Class Safety Evidence Review.

LiveEvidence Review

Review the evidence on whether a drug class is associated with an adverse event across trials, cohorts and spontaneous reports, with certainty rated.

QuestionIs a drug class associated with an adverse event?

EvidenceTrials, cohorts and spontaneous reports

ExpertHead of Pharmacovigilance

Not askedA regulatory action

LengthComprehensive

Drug Class Safety Evidence Review is a ready-made use case for Pharmacovigilance. It ships under the Evidence Review template.

For pharmacovigilance and medical safety leads. You get the PICO, the main studies with effect and risk of bias, certainty per outcome with the reason and what the evidence cannot settle. Studies are cited or marked as gaps.

Add it to your library to reuse from New → From template. Edit the saved copy in your library on the service form.

The decision

What does the published evidence show on whether a named drug class is associated with a named adverse event, from randomized trials, cohort studies and spontaneous report analyses?

What is reviewed

Three kinds of evidence answer different questions, and the review keeps them apart. Trials are rarely powered for rare events, cohorts can estimate risk, and spontaneous reports can only signal.

Evidence	What it holds	What the review does with it
Randomized trials	Pooled adverse event counts, which are often underpowered and may not define the event consistently.^{1Sterne, J. A. C. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019;366:l4898.}	Rated with RoB 2.
Cohort and case-control studies	Risk estimates in routine use, with confounding as the main threat.^{2Sterne, J. A. C. et al. ROBINS-I. BMJ, 2016;355:i4919.}	Rated with ROBINS-I.
Spontaneous report analyses	Disproportionality results such as the proportional reporting ratio, published with criteria of three or more cases, a ratio of at least 2 and a chi-squared of at least 4.^{3Evans, S. J. W., Waller, P. C. and Davis, S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiology and Drug Safety, 2001;10(6):483–486.}	Read as signals and never as risk.
Regulatory process	The EU signal management steps in GVP Module IX, which set what happens after a signal is detected.^{4European Medicines Agency. Guideline on good pharmacovigilance practices (GVP): Module IX – Signal management (Rev. 1). EMA/827661/2011 Rev. 1. Legal effective date 22 November 2017.}	Used to say what a finding would trigger.

What the review does

A signal is not a risk. Reports in a spontaneous database depend on who reports and what is already known. The review labels disproportionality findings as signals and does not convert them into rates.^{3Evans, S. J. W., Waller, P. C. and Davis, S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiology and Drug Safety, 2001;10(6):483–486.}

Studies disagree for reasons. At Comprehensive length the review sets out where trials, cohorts and reports point in different directions, and ties each difference to population, dose, comparator, follow-up or bias.^{1Sterne, J. A. C. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019;366:l4898.,2Sterne, J. A. C. et al. ROBINS-I. BMJ, 2016;355:i4919.}

Thin spots are listed. A matrix of drug by event shows where there is one study or none, so the reader sees where the class effect rests on one member.

Recommended length

Comprehensive

The three kinds of evidence disagree by nature, and the reader needs to see where. Comprehensive adds the section on disagreement and the matrix of thin spots.

You can pick another length on the form. The other two stay available.

Assumptions the review checks

The review states the assumptions its question and its rating rest on, and says what each gap limits. Examples for this question:

The adverse event is defined the same way across studies.
The class effect applies to every member of the class.
Reporting patterns in the database have not changed over the period reviewed.

Standards, guidance and sources

Methods

RoB 2 and ROBINS-I for trials and non-randomized studies.^{1Sterne, J. A. C. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019;366:l4898.,2Sterne, J. A. C. et al. ROBINS-I. BMJ, 2016;355:i4919.}
Evans, Waller and Davis, proportional reporting ratios, 2001.^{3Evans, S. J. W., Waller, P. C. and Davis, S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiology and Drug Safety, 2001;10(6):483–486.}
EMA, GVP Module IX: Signal management (Rev. 1).^{4European Medicines Agency. Guideline on good pharmacovigilance practices (GVP): Module IX – Signal management (Rev. 1). EMA/827661/2011 Rev. 1. Legal effective date 22 November 2017.}

The decision practice behind the memo itself is on the template page.

What gets flagged

Any rate computed from spontaneous reports, any class effect that rests on one drug, and any event defined differently across studies.

What arrives

The question and the bottom line
How the evidence was found
The evidence
What it shows
How strong it is
Where studies disagree
Where the evidence is thin
What the evidence does not answer

What it will not do

It is a rapid review, not a systematic one. It reports the effects the studies reported, does not pool them into a new estimate, and labels every certainty rating as analyst judgment.

It does not decide whether a signal is validated or whether action is needed. That is a safety committee decision.

It is not a systematic review. It uses a bounded search, says so, and recommends a full literature review when completeness matters.

It does not pool studies into a new estimate. It reports the effects the studies reported.

It does not compute a missing interval or plot a missing effect as zero. Both are marked as gaps.

References

[1] Sterne, J. A. C. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ, 2019;366:l4898. Not read.
[2] Sterne, J. A. C. et al. ROBINS-I. BMJ, 2016;355:i4919. Not read.
[3] Evans, S. J. W., Waller, P. C. and Davis, S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiology and Drug Safety, 2001;10(6):483–486. Read from the abstract as summarized in search excerpts.
[4] European Medicines Agency. Guideline on good pharmacovigilance practices (GVP): Module IX – Signal management (Rev. 1). EMA/827661/2011 Rev. 1. Legal effective date 22 November 2017. Scope as given in EMA’s listing found by search; not read in full.

Links checked 9 October 2026

These are the sources the template drew on. None of their authors or issuers has reviewed it.

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