Clinical trial mandate not being followed

Preparing for a clinical trial

Photo by Esther Dyson

A study published in NEJM suggests that results from most trials on ClinicalTrials.gov are not posted on the site within a year of trial completion or termination, even though this violates the Food and Drug Administration Amendments Act (FDAAA) mandate.

Among all the trials analyzed, those funded by industry were the most likely to be publicly disclosed in a timely fashion, researchers found.

Even so, industry compliance with the FDAAA mandate was poor.

And compliance was worse for research funded by the National Institutes of Health (NIH) and other government and academic institutions.

Study authors said this lack of transparency has created a critical information gap about investigational drugs, devices, and biologic therapies that hampers progress and violates obligations to patients.

“Patients who participate in clinical research have the expectation that the risk of participation will be offset by the creation of generalizable knowledge and the advancement of science, and that is achieved through the availability of clinical trial results,” said study author Monique Anderson, MD, of the Duke Clinical Research Institute in Durham, North Carolina.

“Sponsors who lead clinical trials have an ethical and legal obligation to publically report their findings, whether the results are positive or negative.”

In 2000, the US Congress authorized the creation of the ClinicalTrials.gov registry to provide information about clinical trials. Seven years later, the FDAAA mandated that sponsors of most trials begin registering and reporting basic summary results on the registry so the American public could have access to the resulting data.

The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.

To gauge compliance with this mandate, Dr Anderson and her colleagues searched trials posted on ClinicalTrials.gov. They identified 13,327 trials that were likely to be subject to FDAAA provisions and were terminated or completed from January 1, 2008, through August 31, 2012.

Most trials were industry-funded (65.6%), 14.2% were funded by the NIH, and the remaining 20.2% were funded by other government or academic institutions.

In all, 13.4% of trials had results posted on ClinicalTrials.gov within 12 months of trial completion/termination, and 6.1% of trials did not have results reported but had a legally acceptable delay because of a certification or an exemption request.

A higher percentage of trials—38.3%—had results posted on ClinicalTrials.gov at any time during the 5-year study period.

By September 27, 2013, sponsors for 15.8% of all the trials analyzed had submitted a certification or extension request to delay reporting to ClinicalTrials.gov. Of these, 23.0% had results reported during the study period.

At 12 months, 17% of industry-funded trials had results posted on ClinicalTrials.gov, as did 8.1% of trials funded by the NIH, and 5.7% of trials funded by other government or academic institutions. At 5 years, those percentages had increased to 41.5%, 38.9%, and 27.7%, respectively.

“The law requiring public disclosure was enacted amid concerns that sponsors and investigators were selectively publishing trials that favored sponsors’ interests,” Dr Anderson said. “Industry sponsors in particular were criticized for selective reporting.”

“Since the law’s enactment, many companies have developed disclosure policies and have actively pursued expanded public disclosure of data, but there may be a lack of knowledge about the law in academia, or a lack of resources to ensure timely reporting.”

Dr Anderson said penalties for failing to submit data within the 1-year reporting period could be as high as $10,000 a day and/or the loss of NIH funding, but enforcement has not occurred, pending a rule approval.

Preparing for a clinical trial

Photo by Esther Dyson

A study published in NEJM suggests that results from most trials on ClinicalTrials.gov are not posted on the site within a year of trial completion or termination, even though this violates the Food and Drug Administration Amendments Act (FDAAA) mandate.

Among all the trials analyzed, those funded by industry were the most likely to be publicly disclosed in a timely fashion, researchers found.

Even so, industry compliance with the FDAAA mandate was poor.

And compliance was worse for research funded by the National Institutes of Health (NIH) and other government and academic institutions.

Study authors said this lack of transparency has created a critical information gap about investigational drugs, devices, and biologic therapies that hampers progress and violates obligations to patients.

“Patients who participate in clinical research have the expectation that the risk of participation will be offset by the creation of generalizable knowledge and the advancement of science, and that is achieved through the availability of clinical trial results,” said study author Monique Anderson, MD, of the Duke Clinical Research Institute in Durham, North Carolina.

“Sponsors who lead clinical trials have an ethical and legal obligation to publically report their findings, whether the results are positive or negative.”

In 2000, the US Congress authorized the creation of the ClinicalTrials.gov registry to provide information about clinical trials. Seven years later, the FDAAA mandated that sponsors of most trials begin registering and reporting basic summary results on the registry so the American public could have access to the resulting data.

The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.

To gauge compliance with this mandate, Dr Anderson and her colleagues searched trials posted on ClinicalTrials.gov. They identified 13,327 trials that were likely to be subject to FDAAA provisions and were terminated or completed from January 1, 2008, through August 31, 2012.

Most trials were industry-funded (65.6%), 14.2% were funded by the NIH, and the remaining 20.2% were funded by other government or academic institutions.

In all, 13.4% of trials had results posted on ClinicalTrials.gov within 12 months of trial completion/termination, and 6.1% of trials did not have results reported but had a legally acceptable delay because of a certification or an exemption request.

A higher percentage of trials—38.3%—had results posted on ClinicalTrials.gov at any time during the 5-year study period.

By September 27, 2013, sponsors for 15.8% of all the trials analyzed had submitted a certification or extension request to delay reporting to ClinicalTrials.gov. Of these, 23.0% had results reported during the study period.

At 12 months, 17% of industry-funded trials had results posted on ClinicalTrials.gov, as did 8.1% of trials funded by the NIH, and 5.7% of trials funded by other government or academic institutions. At 5 years, those percentages had increased to 41.5%, 38.9%, and 27.7%, respectively.

“The law requiring public disclosure was enacted amid concerns that sponsors and investigators were selectively publishing trials that favored sponsors’ interests,” Dr Anderson said. “Industry sponsors in particular were criticized for selective reporting.”

“Since the law’s enactment, many companies have developed disclosure policies and have actively pursued expanded public disclosure of data, but there may be a lack of knowledge about the law in academia, or a lack of resources to ensure timely reporting.”

Dr Anderson said penalties for failing to submit data within the 1-year reporting period could be as high as $10,000 a day and/or the loss of NIH funding, but enforcement has not occurred, pending a rule approval.

Preparing for a clinical trial

Photo by Esther Dyson

A study published in NEJM suggests that results from most trials on ClinicalTrials.gov are not posted on the site within a year of trial completion or termination, even though this violates the Food and Drug Administration Amendments Act (FDAAA) mandate.

Among all the trials analyzed, those funded by industry were the most likely to be publicly disclosed in a timely fashion, researchers found.

Even so, industry compliance with the FDAAA mandate was poor.

And compliance was worse for research funded by the National Institutes of Health (NIH) and other government and academic institutions.

Study authors said this lack of transparency has created a critical information gap about investigational drugs, devices, and biologic therapies that hampers progress and violates obligations to patients.

“Patients who participate in clinical research have the expectation that the risk of participation will be offset by the creation of generalizable knowledge and the advancement of science, and that is achieved through the availability of clinical trial results,” said study author Monique Anderson, MD, of the Duke Clinical Research Institute in Durham, North Carolina.

“Sponsors who lead clinical trials have an ethical and legal obligation to publically report their findings, whether the results are positive or negative.”

In 2000, the US Congress authorized the creation of the ClinicalTrials.gov registry to provide information about clinical trials. Seven years later, the FDAAA mandated that sponsors of most trials begin registering and reporting basic summary results on the registry so the American public could have access to the resulting data.

The requirement covers non-phase-1 trials of drugs, medical devices, or biologics that had at least 1 US research site. Trial results are to be reported by the sponsor within a year of completing data collection.

To gauge compliance with this mandate, Dr Anderson and her colleagues searched trials posted on ClinicalTrials.gov. They identified 13,327 trials that were likely to be subject to FDAAA provisions and were terminated or completed from January 1, 2008, through August 31, 2012.

Most trials were industry-funded (65.6%), 14.2% were funded by the NIH, and the remaining 20.2% were funded by other government or academic institutions.

In all, 13.4% of trials had results posted on ClinicalTrials.gov within 12 months of trial completion/termination, and 6.1% of trials did not have results reported but had a legally acceptable delay because of a certification or an exemption request.

A higher percentage of trials—38.3%—had results posted on ClinicalTrials.gov at any time during the 5-year study period.

By September 27, 2013, sponsors for 15.8% of all the trials analyzed had submitted a certification or extension request to delay reporting to ClinicalTrials.gov. Of these, 23.0% had results reported during the study period.

At 12 months, 17% of industry-funded trials had results posted on ClinicalTrials.gov, as did 8.1% of trials funded by the NIH, and 5.7% of trials funded by other government or academic institutions. At 5 years, those percentages had increased to 41.5%, 38.9%, and 27.7%, respectively.

“The law requiring public disclosure was enacted amid concerns that sponsors and investigators were selectively publishing trials that favored sponsors’ interests,” Dr Anderson said. “Industry sponsors in particular were criticized for selective reporting.”

“Since the law’s enactment, many companies have developed disclosure policies and have actively pursued expanded public disclosure of data, but there may be a lack of knowledge about the law in academia, or a lack of resources to ensure timely reporting.”

Dr Anderson said penalties for failing to submit data within the 1-year reporting period could be as high as $10,000 a day and/or the loss of NIH funding, but enforcement has not occurred, pending a rule approval.