Human drug trials are compromised by poor reporting of animal research

Poor animal study design and reporting thwarts the ethical review of proposed human drug trials, according to a study led by researchers at Hannover Medical School, Germany, in cooperation with researchers from McGill University, Canada. The study, publishing 5 April in the open access journal PLOS Biology, analyzed the descriptions of animal studies found in "investigator brochures" - the documents used by regulatory authorities and ethics committees to assess the potential efficacy of drugs that are being tested in patients for the first time.

Independent assessments of animal evidence are key to ensuring that patients are not exposed to undue risk when volunteering in trials. Based on documents obtained from three prominent German medical research centers, the study authors recommend that regulators need to develop standards to ensure the rigorous design and reporting of preclinical animal studies when trials of new drugs are launched.

Strikingly, less than one-fifth of investigator brochures referenced animal studies that had been through a peer-reviewed publication process. Less than 20% of animal studies that tested the efficacy of the new drug described the use of simple techniques, like randomization blinding or sample size calculation, that can reduce the effects of bias. And worryingly, of the more than 700 animal studies that the authors found in the investigator brochures, only 4% did not show positive effects of treatment.

"Our analysis shows that the vast majority of these documents lack the information needed to systematically appraise the strength of evidence supporting trials," said Dr Daniel Strech, professor for bioethics at Hannover Medical School and senior author of the study.

"We were also struck by the rarity of 'negative' animal studies in investigator brochures", said Jonathan Kimmelman, professor for bioethics at McGill University and co-author. "With a median group size of 8 animals, these studies had limited ability to measure treatment effects precisely. Chance alone should have resulted in more studies being negative- the imbalance strongly suggests publication bias" said Susanne Wieschowski, a postdoctoral fellow in Strech's team.

"Why do regulatory agencies and other bodies involved in risk-benefit assessment for early human research accept the current situation?" asks Daniel Strech. "Why do they not complain about the lack of information needed to critically appraise the rigor of the preclinical efficacy studies and about the concerning lack of efficacy studies demonstrating no effects?"

Wieschowski S, Chin WWL, Federico C, Sievers S, Kimmelman J, Strech D.
Preclinical efficacy studies in investigator brochures: Do they enable risk-benefit assessment?
PLoS Biol. 2018 Apr 5;16(4):e2004879. doi: 10.1371/journal.pbio.2004879.

Most Popular Now

Novartis rises to second place in 2018 Access to M…

Novartis ranked second in the 2018 Access to Medicine Index (ATMi), up from 3rd place in 2016, in recognition of its long-standing efforts to improve worldwide access to ...

MSD is looking for a digital health solution to em…

MSD Lebanon is looking for an external partner to co-create a digital solution that helps oncologists to stay updated with relevant clinical content about cancer. The sol...

Sanofi builds focus on rare blood disorders and ca…

Some of the most serious unmet patient needs today are in the field of hematology. Rare blood disorders and blood-related cancers continue to be a major focus of research...

Lilly submits New Drug Application to the FDA for …

Eli Lilly and Company (NYSE: LLY) has announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lasmiditan for the acute...

FDA approves new treatment for patients with acute…

The U.S. Food and Drug Administration today approved Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for t...

New study reveals probiotics do not help children …

Probiotics are a multibillion-dollar industry with marketing claims of being an effective treatment for a multitude of ailments, including diarrhea. However, findings fro...

Merck and Pfizer provide update on avelumab in pla…

Merck and Pfizer Inc. (NYSE: PFE) today announced that the Phase III JAVELIN Ovarian 200 trial evaluating avelumab* alone or in combination with pegylated liposomal doxor...

U.S. FDA approves Larotrectinib, the first TRK inh…

The U.S. Food and Drug Administration (FDA) has approved larotrectinib, the first oral TRK inhibitor, under the brand name Vitrakvi®. The approval is for the treatment of...

Bristol-Myers Squibb awards "Golden Tickets…

Bristol-Myers Squibb Company (NYSE: BMY) and LabCentral, an innovative, shared laboratory space designed as a launchpad for life-sciences and biotech startups, today anno...

FDA approves first treatment for Lambert-Eaton mya…

The U.S. Food and Drug Administration today approved Firdapse (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in adults. LEMS is a r...

Alcon to highlight its vision, strategy and benefi…

Alcon, the eye care division of Novartis, will today hold its first Capital Markets Day for investors and analysts in relation to the previously-announced intention of No...

Scorpion venom to shuttle drugs into the brain

The Peptides and Proteins lab at the Institute for Research in Biomedicine (IRB Barcelona) has published a paper in Chemical Communications describing the capacity of a s...