Cookie policy: This site uses cookies (small files stored on your computer) to simplify and improve your experience of this website. Cookies are small text files stored on the device you are using to access this website. For more information please take a look at our terms and conditions. Some parts of the site may not work properly if you choose not to accept cookies.


Subscribe or Register

Existing user? Login


Adverse drug events

Low risks to volunteers from phase I clinical drug trials, study shows

Researchers find that only 0.31% of volunteers participating in non-cancer phase I clinical trials for new drugs saw serious complications.

Fears over the risk of serious harms to volunteers in non-oncology phase 1 trials are unjustified, according to the results of a meta-analysis published. In the image, three volunteers during a Phase 1 trial

Source: age fotostock / Alamy

Female volunteers were more likely than male volunteers to experience an adverse event in phase I trials, researchers found

Fears over the risk of serious harms to volunteers in non-oncology phase I trials are unjustified, according to the results of a meta-analysis published in The BMJ[1].

Critics of phase I research trials claim that healthy volunteers are exposed to risks of serious harms in the absence of any clinical benefit, but little research has quantified the risks in this cohort. More than 100,000 healthy volunteers have participated in non-oncology phase I investigations annually worldwide.

Bioethicist Ezekiel Emanuel from the University of Pennsylvania wanted to quantify the frequency and seriousness of adverse events in non-oncology phase I studies with healthy volunteers, not patients. His team analysed data from phase I studies conducted between 2004 and 2011 at Pfizer’s phase I clinical testing sites in Belgium, Singapore and the United States.

The researchers found that out of 11,028 healthy volunteers who were given a study drug in 394 non-oncology phase I research studies, 0.31% (or 34) experienced a serious adverse event. The majority — or 84.6% (20,840) — of adverse events were mild, with more than 10% of adverse events occurring after volunteers received placebos. The researchers found no deaths or life-threatening events. The most common adverse events were headache, tiredness or drowsiness, diarrhoea, nausea and dizziness. Of the 34 serious adverse events, half were related to the study, with 11 caused by the study drug itself and seven caused by surgical or medical interventions related to the trial, such as spinal taps. Other serious adverse events unrelated to the drug included dengue haemorrhagic fever and appendicitis.

Certain factors were associated with a greater risk of adverse effects: for example, women were significantly more likely than men to experience an adverse event (80% versus 62%). Researchers found participants with a history of alcohol consumption were more likely to experience an adverse event than those without (69% versus 60%), but this did not apply for those with a smoking history (64% in both groups).

“Because of some high profile cases, such as TeGenero, there is the perception that early phase research is very risky,” says Emanuel. “But there are not a lot of data.” In 2006, German firm TeGenero saw its experimental drug TGN1412 cause multiple organ failure in six men during a clinical trial in England.

“Our study of over 11,000 healthy volunteers in phase I studies suggests these studies have very limited risks,” says Emanuel. “There were no deaths or permanent disabilities. Only 0.3% of volunteers experience serious adverse events as defined by the US Food and Drug Administration and half of these, such as dengue fever, were not related to the experimental drugs or procedures.

“A third of volunteers experienced no adverse events. Society needs to change its perceptions about early stage research with healthy volunteers,” he adds.

Responding to the report, Virginia Acha, executive director research, medical and innovation for the Association of the British Pharmaceutical Industry, says phase I studies for non-oncology drugs in healthy volunteers are an important part of the drug development process for the pharmaceutical industry.

“They do not offer any clinical benefit to trial participants, but are carried out to determine whether a drug is safe in humans, and to determine what the body does to the drug and what the drug does to the body,” says Acha.

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2015.20069008

Have your say

For commenting, please login or register as a user and agree to our Community Guidelines. You will be re-directed back to this page where you will have the ability to comment.

Recommended from Pharmaceutical Press

  • Clinical Pharmacokinetics

    Clinical Pharmacokinetics

    A practical guide to the use of pharmacokinetic principles in clinical practice. Includes case studies with questions and answers.

    £33.00Buy now
  • Drugs of Abuse

    Drugs of Abuse

    A concise, easy-to-read guide for healthcare professionals who encounter drug abuse.

    £38.00Buy now
  • Pharmaceutical Toxicology

    Pharmaceutical Toxicology

    Explains the methodology and requirements of pre-clinical safety assessments of new medicines. Includes registration requirements and pharmacovigilance.

    £40.00Buy now
  • Adverse Drug Reactions

    Adverse Drug Reactions

    A practical guide to the drug reactions that affect particular organ systems, and the management of these reactions.

    £38.00Buy now
  • English Delftware Drug Jars

    English Delftware Drug Jars

    This beautiful book illustrates the art and history of the collection of English delftware drug jars in the Museum of the Royal Pharmaceutical Society of Great Britain.

    £54.00Buy now
  • Print
  • Share
  • Comment
  • Save
  • Print Friendly Version of this pagePrint Get a PDF version of this webpagePDF

Supplementary images

  • Fears over the risk of serious harms to volunteers in non-oncology phase 1 trials are unjustified, according to the results of a meta-analysis published. In the image, three volunteers during a Phase 1 trial

Newsletter Sign-up

Want to keep up with the latest news, comment and CPD articles in pharmacy and science? Subscribe to our free alerts.