Pre-emptive or reactive testing? Two strategies for pharmacogenetics

Reviewed by Dr. Daniel Wallerstorfer, molecular biologist and founder of Novogenia · Updated: 13 October 2026 · Reading time: 9 min

In short

Reactive means testing when a specific drug is due or problems arise. Pre-emptive means determining a panel of many genes once and using it again for later prescriptions – because genes do not change over a lifetime. The European PREPARE trial with 6,944 people showed that with a 12-gene panel, clinically relevant adverse drug reactions occurred less often (21.0% versus 27.7% among people with an actionable result). Which strategy fits depends on medication, age and the clinical question. Decisions about treatment are made by the treating physician.

6,944 people, twelve genes, one clear signal

What happens when physicians and pharmacies know, at the very first prescription, how a person’s body handles many drugs? The European PREPARE trial put this to the test – in 18 hospitals, nine community health centers and 28 community pharmacies across seven countries: Austria, Greece, Italy, the Netherlands, Slovenia, Spain and the UK.

The trial enrolled 6,944 adults who were starting a drug for which the Dutch DPWG gives a gene-based recommendation. 3,342 of them received genotype-guided treatment: the lab determined an entire panel of 50 variants in twelve genes. If the result showed an actionable gene–drug combination, treatment followed the DPWG recommendations. 3,602 people received standard care. To keep the comparison fair, the participating sites switched between the two approaches according to a fixed schedule. And so that local teams could work with the results, they were trained at the start and given online learning material.

The result after twelve weeks: among people with an actionable result for their drug, a clinically relevant adverse drug reaction occurred in 21.0% of the panel group and 27.7% of the control group. Across all participants, the figures were 21.5% versus 28.6%. In both cases, the odds of such a reaction were 30% lower (odds ratio 0.70). And the approach worked across very different European health care systems (Swen et al., Lancet, 2023).

The logical conclusion: a panel works like a known blood type. Once determined, the information is ready whenever it is needed – at the next prescription, at the pharmacy, in the hospital. Still, not every situation calls for a panel. Here is how the two strategies differ and when each one makes sense.

Two strategies compared

Reactive and pre-emptive testing are not opposites but two tools for different situations:

Feature	Reactive	Pre-emptive (panel)
Timing	when a specific drug is due or problems arise	before any medication is due, or at the first relevant prescription
Scope	one gene or a few genes for the question at hand	many genes at once
Time pressure	The result must be in before treatment starts.	The result is already available.
Value over time	answers the current question	also answers later questions
Typical example	DPYD before chemotherapy with fluoropyrimidines	polypharmacy, foreseeable long-term therapies
What to watch	allow for sample shipping and lab time	document so the result can be found again

Reactive: a targeted look before a therapy

The reactive test is the classic. One clear question, one clear gene: before chemotherapy with fluoropyrimidines, DPYD shows whether the starting dose should be adjusted. Before clopidogrel after acute coronary syndrome or PCI, CYP2C19 shows whether the body activates the prodrug sufficiently. The studies behind this are presented in Pharmacogenetics in medical practice.

A second trigger is surprises: a drug does not work at a normal dose, or it causes strong side effects even at a low dose. A test can then help to understand the cause better – alongside all the other explanations the physician considers.

Two points belong in the planning:

Time: The result should be available before treatment starts. Allow for sample shipping and lab time. Whether a therapy can wait until then is a clinical judgment.
Reach: A single-gene test answers exactly one question. If a drug that depends on a different gene comes up later, another test is needed.

Pre-emptive: test once, look it up again and again

The pre-emptive approach thinks further ahead. An analysis of more than 73 million patient records from the US shows how often people receive drugs for which pharmacogenetic guidelines exist: among people aged 65 and over with Medicare Supplemental coverage and among Medicaid patients aged 40 to 64, about half received at least one such drug within four years, and a quarter to a third received two or more (Samwald et al., PLoS One, 2016).

On top of that, actionable variants are common. In a Dutch pharmacy study, 90% of the 200 people tested carried at least one result with an actionable recommendation – with a panel of just 8 genes (Bank et al., European Journal of Human Genetics, 2019). The follow-up of the same study shows how well a panel, once determined, comes back into play in everyday care. After an average of 2.5 years, 97% of the 200 patients could use their panel result for at least one new prescription with a possible gene link, and 33% for up to four. For 24.2% of these new prescriptions, the result showed that the therapy should be adjusted (van der Wouden et al., Genes, 2019).

For practice, this means: genes do not change over a lifetime. A panel therefore answers not just today’s question but many of tomorrow’s – with no new sample and no waiting. And PREPARE showed that exactly this approach can be implemented in hospitals, health centers and pharmacies across Europe.

Which strategy fits? A decision aid

The studies suggest some practical rules of thumb – logical conclusions, not rigid requirements:

Lean toward reactive: a single drug with a clear gene-based recommendation is about to start, and no further long-term therapies are foreseeable.
Lean toward pre-emptive: several drugs are already being taken, age or chronic conditions make further prescriptions likely, or therapies are coming up in which several genes play a role.
Combine both: as in PREPARE, the first prescription of a drug with a gene-based recommendation can be the trigger to determine a whole panel right away. That way, one test answers the current question and lays the groundwork for later ones.

You make the decision together with your patient. Who may order a test differs from country to country – in Switzerland, pharmacists may too, under certain conditions. The short version is in Pharmacogenetics in the pharmacy, the details in Law: who may offer pharmacogenetics?

What a panel does not replace

As useful as a panel is, it is a tool for the physician’s decision, not a substitute for it. Three things remain important even with the best result:

The overall clinical picture: Age, kidney and liver function, and other drugs that slow down the same enzyme change the effect as well. Genes are one factor among many.
The reach of the test: A panel only tells you about the genes and variants it actually examines. What was not read remains an open question.
Follow-up: You keep monitoring effect and tolerability as usual. Recommendations from a genetic profile are logical conclusions that should be confirmed over the course of treatment.

Making a panel pay off: documentation

A panel is only as valuable as it is easy to find. A result that disappears into a folder helps no one at the next prescription. These steps make sure it is there when it is needed:

Plan consent with the future in mind: In Germany, consent also covers whether, and to what extent, the result is disclosed or destroyed (Section 8(1) GenDG). So bring up later use at that point. More in Data protection and consent.
Permanently in the record: gene, genotype, phenotype and date, visible with every new prescription.
With the patient: a short summary they can show at the pharmacy and to other physicians.
At the pharmacy: recorded with consent, so that prescriptions from other practices are checked too.
Read with current knowledge: The genotype stays; the guidelines evolve. Interpret the result according to current knowledge with every new prescription – Understanding and communicating results shows how.

Checklist: choosing the right strategy

The current question is clear: which drug, which gene, how urgent.
Foreseeable future therapies are taken into account: polypharmacy, age, chronic conditions.
The choice between a single-gene test and a panel has been discussed with the patient.
For a reactive test, sample shipping and lab time are planned before treatment starts.
Consent also covers what happens to the result later.
The result is documented permanently and shared with the pharmacy with consent.
With every new prescription, the result is interpreted according to current guidelines.
Every change to medication is decided by the treating physician.

Frequently asked questions

What is the difference between pre-emptive and reactive pharmacogenetic testing?

Reactive testing happens when a specific question comes up: a particular drug, an unexpected side effect or a lack of effect. It usually involves one gene or a few. Pre-emptive testing determines a panel of many genes before the questions arise. The result is then already available for later prescriptions.

What did the PREPARE trial show?

In the European PREPARE trial, 6,944 people starting a drug with a DPWG recommendation were treated either with the help of a 12-gene panel or as usual. Among people with an actionable result, clinically relevant adverse drug reactions occurred in 21.0% of the panel group and 27.7% of the control group; the odds ratio was 0.70 (Swen et al., Lancet, 2023).

Does a panel make sense for people who take no medication today?

That is a case-by-case decision. Genes do not change, so a panel can still answer questions years later. Data from the US show that older people in particular often receive drugs for which pharmacogenetic guidelines exist. Whether a test makes sense is something you decide together with your patient.

Does a panel have to be repeated after a few years?

For the variants tested, usually not, because genes stay the same. What changes are the guidelines: the same genotype can be interpreted according to current knowledge with each new prescription. A new test can make sense if important genes or variants were not covered at the time.

How do I make sure a panel result is taken into account later?

Enter the gene, genotype and phenotype as a permanent entry in the record, give your patient a short summary, and share the result with their pharmacy with consent. In Germany, consent already covers whether, and to what extent, the result is to be disclosed or destroyed (Section 8(1) GenDG).

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Note: This guide is general information for businesses and professionals and does not replace medical or legal advice. The genetic traits determined in a genetic analysis are well documented (each gene included is backed by at least three independent studies); recommendations derived from them are logical conclusions, not scientifically proven. Pharmacogenetic results do not replace a medical decision: any change to medication is made only by the treating physician. Regulations can change; errors and changes excepted.