Some serious risks in boxed warnings went undisclosed in patient consent forms
by Sarah Wickline Wallan
Staff Writer, MedPage Today 7-28-15
Not all postmarketing drug trials conducted at one major research institution gave patients consent forms that disclosed important risks, including those contained in boxed warnings, researchers found.
Over the course of 2 years, 63% of patient consent forms for projects approved by an institutional review board (IRB), involving 57 projects testing 17 different drugs, did not disclose one or more relevant boxed warning label risks to trial participants, reported Steven M. Belknap, MD, of Northwestern University in Chicago, and colleagues, who wrote in a research letter in JAMA Internal Medicine.
"Considerable time and effort are invested by these IRBs, as well as by investigators and research staff, to ensure compliance with the aforementioned principles and guidelines [respect for persons, beneficence, and justice]," pointed out Joseph S. Ross, MD, MHS, of Yale School of Medicine in New Haven, Conn., in an accompanying editor's note. "But how effective have we been?"
The research letter authors "should be applauded for publicly examining and reporting on this problem identified at their IRB, but there is no reason to think the problem is an isolated one," Ross added.
Belknap and colleagues looked at their institution's IRB database, and found 4,780 human biomedical research projects that were active from 2010 through 2012. The researchers then found 44 boxed warning labels with risks that were applicable to 57 protocols involving 17 different drugs, including epoetin alfa, everolimus (Afinitor), estradiol, ciprofloxacin, methadone, hydrocodone-acetaminophen, clopidogrel (Plavix), sunitinib (Sutent), telaprevir (Incivek), and salmeterol.
Of these 57 studies, 75% involved patients with life-threatening diseases, and 63% did not disclose boxed warning risks to those patients. Among those 36 trials, 19 were conducted across multiple centers.
Next, Belknap's team looked at how the projects were funded. "Sponsors and investigators have inherent conflicts of interest, as clinical trials may generate income or enhance reputation," they explained.
For research that was not sponsored by industry or a government agency, which accounted for 21 of the 57 studies, 81% did not disclose boxed warnings to participants. Among the 16 industry-sponsored research studies, 56% did not provide disclosures. And of the 20 government-agency sponsored research, half did not disclose boxed warning label risks.
The differences in nondisclosure rates between unsponsored research versus government-agency sponsored research was steeper at 81% versus 50% compared with other pairings (P<0.05). None of the other pair comparisons reached statistical significance (P>0.16).
"The higher nondisclosure rate of boxed warnings in nonsponsored research compared with government agency-sponsored research may reflect procedural variability, as sponsored research projects typically involve multiple levels of internal and external review," Belknap and colleagues wrote.
Belknap's team noted that IRBs have vital roles in patient safety that include "mitigation of misaligned motives, blurred roles, and asymmetries in information and power." Their findings that some serious risks in boxed warnings went undisclosed in the patient consent forms "is an impediment to medical progress."
Furthermore, the distrust created by lack of disclosure has the potential to scare patients away from participating in medical research "if they fear that there may be undisclosed risks."
"Studies of these higher-risk medications were infrequent," Ross noted. "However, because these studies lacked disclosure of the safety risk, they can neither have ensured true informed consent nor provided a full assessment of the risks and benefits of study participation."
Belknap and co-authors disclosed no relevant relationships with industry.
Ross is an associate editor at JAMA Internal Medicine. He disclosed no relevant relationships with industry.
by Sarah Wickline Wallan
Staff Writer, MedPage Today 7-28-15
Not all postmarketing drug trials conducted at one major research institution gave patients consent forms that disclosed important risks, including those contained in boxed warnings, researchers found.
Over the course of 2 years, 63% of patient consent forms for projects approved by an institutional review board (IRB), involving 57 projects testing 17 different drugs, did not disclose one or more relevant boxed warning label risks to trial participants, reported Steven M. Belknap, MD, of Northwestern University in Chicago, and colleagues, who wrote in a research letter in JAMA Internal Medicine.
"Considerable time and effort are invested by these IRBs, as well as by investigators and research staff, to ensure compliance with the aforementioned principles and guidelines [respect for persons, beneficence, and justice]," pointed out Joseph S. Ross, MD, MHS, of Yale School of Medicine in New Haven, Conn., in an accompanying editor's note. "But how effective have we been?"
The research letter authors "should be applauded for publicly examining and reporting on this problem identified at their IRB, but there is no reason to think the problem is an isolated one," Ross added.
Belknap and colleagues looked at their institution's IRB database, and found 4,780 human biomedical research projects that were active from 2010 through 2012. The researchers then found 44 boxed warning labels with risks that were applicable to 57 protocols involving 17 different drugs, including epoetin alfa, everolimus (Afinitor), estradiol, ciprofloxacin, methadone, hydrocodone-acetaminophen, clopidogrel (Plavix), sunitinib (Sutent), telaprevir (Incivek), and salmeterol.
Of these 57 studies, 75% involved patients with life-threatening diseases, and 63% did not disclose boxed warning risks to those patients. Among those 36 trials, 19 were conducted across multiple centers.
Next, Belknap's team looked at how the projects were funded. "Sponsors and investigators have inherent conflicts of interest, as clinical trials may generate income or enhance reputation," they explained.
For research that was not sponsored by industry or a government agency, which accounted for 21 of the 57 studies, 81% did not disclose boxed warnings to participants. Among the 16 industry-sponsored research studies, 56% did not provide disclosures. And of the 20 government-agency sponsored research, half did not disclose boxed warning label risks.
The differences in nondisclosure rates between unsponsored research versus government-agency sponsored research was steeper at 81% versus 50% compared with other pairings (P<0.05). None of the other pair comparisons reached statistical significance (P>0.16).
"The higher nondisclosure rate of boxed warnings in nonsponsored research compared with government agency-sponsored research may reflect procedural variability, as sponsored research projects typically involve multiple levels of internal and external review," Belknap and colleagues wrote.
Belknap's team noted that IRBs have vital roles in patient safety that include "mitigation of misaligned motives, blurred roles, and asymmetries in information and power." Their findings that some serious risks in boxed warnings went undisclosed in the patient consent forms "is an impediment to medical progress."
Furthermore, the distrust created by lack of disclosure has the potential to scare patients away from participating in medical research "if they fear that there may be undisclosed risks."
"Studies of these higher-risk medications were infrequent," Ross noted. "However, because these studies lacked disclosure of the safety risk, they can neither have ensured true informed consent nor provided a full assessment of the risks and benefits of study participation."
Belknap and co-authors disclosed no relevant relationships with industry.
Ross is an associate editor at JAMA Internal Medicine. He disclosed no relevant relationships with industry.