The trial was conducted at the Texas Back Institute in Plano, Texas, on 304 patients, and was led by a team of surgeons that included Dr Scott Blumenthal, Dr Barton Sachs, and Dr Stephen Hochschuler, who are considered to be among the best spine surgeons in the field. Dr Blumenthal presented the results of the trial at a hearing before an FDA advisory panel.
A transcript of the June 2, 2004, hearing, reveals the agency's own reviewer found the study to be biased in favor of Charite, and that important data about patients had been excluded. A voting member of the panel, Brent Blumenstein, complained about omitted patients during the hearing, but went on to vote for approval anyways.
In a nutshell, the study basically showed no significant differences in complications between the Charite group and the spinal fusion group.
According to Sergio del Castillo, a biochemical engineer, and the FDA's lead reviewer of the Charite approval application, the "purpose of the study was to evaluate the safety and effectiveness of the Charite and compare it to the BAK Interbody Fusion device."
The study was to show that the Charite would be at least as good as the BAK within a non-inferiority margin of 15%, Mr del Castillo explained, and was not designed to demonstrate superiority of one group over the other.
The first five subjects at each investigational site were treated with the Charite as part of the training of the surgeons and they were not included in the final assessment of effectiveness of the devices.
The success rates for the Charite and the BAK groups were 64% and 58 percent, respectively. Considering the overall success rate is within a non-inferiority margin of 10% of the BAK success rate, "it appears the study has demonstrated the non-inferiority of the Charite compared to the BAK," Mr del Castillo told the panel.
Adverse events in the study, he explained, were categorized as typical or unusual, severe or life threatening, device related or not device related, severe and device related occurring within two days of surgery and by date of onset.
The percentage of Charite and BAK subjects experiencing at least one adverse event, he said, was essentially equal. However, Mr del Castillo said some adverse events were reported in a higher percentage of Charite subjects compared to the BAK group, and included infection, abdominal events, device related events and severe life threatening events.
He noted that 7.3% of Charite subjects experienced adverse events compared to 4% of BAK subjects. A greater percentage of Charite patients experienced: (1) back or lower extremity pain; (2) neurological events, such as numbness, motor deficit or nerve root injury; and (3) additional surgery at the index level.
It should be noted, he advised, that the rate of adverse events was higher in the training group compared to the randomized subjects in the study and pointed out that training subjects were not included in the assessment of safety.
Safety and effectiveness in the study were evaluated in terms of the complications that arose during implantation and post-operatively including infection, thrombosis, migration and subsidence, re-operation, the incidence of adverse events, the level of the subject's disability and assessment of the subject's neurological status.
The primary endpoint for effectiveness consisted of four components: (1) pain in function as measured by the ODI; (2) any device failures requiring revision, re-operation or removal; (3) any major complications; and (4) neurological status.
A surgery was determined to be a success if the subjects: (1) ODI score increased by at least 25% at 24 months compared to the subject's baseline score; (2) experienced no device failures requiring revision, re-operation or removal; (3) did not experience any major complications defined as major blood vessel injury, neurological damage or nerve root injury; and (4) the subject's neurological status was maintained or improved at 24 months with no new permanent neurological deficits compared to baseline.
An individual subject was considered a success only if he or she was a success in all four components, Mr del Castillo advised the panel.
The study was defined as a success if the success rate of the Charite group was found to be non-inferior to the overall success rate of the BAK group, and safety was assessed by comparing the rate of incidence of all adverse events observed in the two groups.
A transcript of the June 2, 2004, hearing, reveals the agency's own reviewer found the study to be biased in favor of Charite, and that important data about patients had been excluded. A voting member of the panel, Brent Blumenstein, complained about omitted patients during the hearing, but went on to vote for approval anyways.
In a nutshell, the study basically showed no significant differences in complications between the Charite group and the spinal fusion group.
According to Sergio del Castillo, a biochemical engineer, and the FDA's lead reviewer of the Charite approval application, the "purpose of the study was to evaluate the safety and effectiveness of the Charite and compare it to the BAK Interbody Fusion device."
The first five subjects at each investigational site were treated with the Charite as part of the training of the surgeons and they were not included in the final assessment of effectiveness of the devices.
The success rates for the Charite and the BAK groups were 64% and 58 percent, respectively. Considering the overall success rate is within a non-inferiority margin of 10% of the BAK success rate, "it appears the study has demonstrated the non-inferiority of the Charite compared to the BAK," Mr del Castillo told the panel.
Adverse events in the study, he explained, were categorized as typical or unusual, severe or life threatening, device related or not device related, severe and device related occurring within two days of surgery and by date of onset.
The percentage of Charite and BAK subjects experiencing at least one adverse event, he said, was essentially equal. However, Mr del Castillo said some adverse events were reported in a higher percentage of Charite subjects compared to the BAK group, and included infection, abdominal events, device related events and severe life threatening events.
He noted that 7.3% of Charite subjects experienced adverse events compared to 4% of BAK subjects. A greater percentage of Charite patients experienced: (1) back or lower extremity pain; (2) neurological events, such as numbness, motor deficit or nerve root injury; and (3) additional surgery at the index level.
It should be noted, he advised, that the rate of adverse events was higher in the training group compared to the randomized subjects in the study and pointed out that training subjects were not included in the assessment of safety.
Safety and effectiveness in the study were evaluated in terms of the complications that arose during implantation and post-operatively including infection, thrombosis, migration and subsidence, re-operation, the incidence of adverse events, the level of the subject's disability and assessment of the subject's neurological status.
The primary endpoint for effectiveness consisted of four components: (1) pain in function as measured by the ODI; (2) any device failures requiring revision, re-operation or removal; (3) any major complications; and (4) neurological status.
A surgery was determined to be a success if the subjects: (1) ODI score increased by at least 25% at 24 months compared to the subject's baseline score; (2) experienced no device failures requiring revision, re-operation or removal; (3) did not experience any major complications defined as major blood vessel injury, neurological damage or nerve root injury; and (4) the subject's neurological status was maintained or improved at 24 months with no new permanent neurological deficits compared to baseline.
An individual subject was considered a success only if he or she was a success in all four components, Mr del Castillo advised the panel.
The study was defined as a success if the success rate of the Charite group was found to be non-inferior to the overall success rate of the BAK group, and safety was assessed by comparing the rate of incidence of all adverse events observed in the two groups.
(Note: You can view every article as one long page if you sign up as an Advocate Member, or higher).
