Trials Data - Part V: Answer

Matthew writes exclusively for Seroxat Sufferers

Read part IV before you do anything else.

Advanced Bromide Consumption plc do not exist... this is merely an exercise (in the essay sense)



Trials Data - Part V: Answer

Advanced Bromide Consumption plc is a large pharmaceutical company with a product portfolio covering a wide range of medicines, amongst other things...

...Discuss the criminal liability, if any, of Advanced Bromide Consumption, Dave, Edwina, Fatima, Good Healthy Information and Jake and his colleagues.




We are not provided detail of the trials' authorization process, including the location of said trials, which would impact on any liability under Regulations 33 and 34. Nor are we told when the trials were carried out. As such, the writer humbly proceeds on the assumption that the Regulations were in force when the trials were authorized; that applications have been properly submitted and authorized, under Regulation 12; that the trials were properly terminated, under Regulation 27; conducted in accordance with the protocol, under Regulation 29; conducted in accordance with good clinical practice, under Regulation 28; that any breaches have been properly notified under Regulation 29A; that qualified person(s) were in place to carry out the duties specified by Art 13(3) and (4) of the Clinical Trials Directive, under Regulation 43; and that proper labelling of the product was carried out under Regulation 49.

The first question, then, that presents itself, concerns that of whether Advanced Bromide, as sponsor, has made proper notification and report of any SAEs that came to its attention, during the course of the trials that it conducted. Under the Regulations, the investigators would be obliged to report the Serious Adverse Events ("SAEs") to the sponsor promptly. Again, this detail is not provided, but the writer assumes that this has been done. If it has not been done, then the investigators may be liable, under Regulation 32, and they may also be liable for not submitting a written report to the sponsor.

If the investigators have reported the serious adverse events properly, then we have to speculate as to whether or not the sponsor has advised the regulator (which may be done by entering the incidents on the European database) under Regulation 33. However, the Regulations state that a SAE has to be fatal or life-threatening for Regulation 33 to apply. And unless one conceives that suicidal ideations will lead eventually to suicide, then merely thinking about suicide will not qualify, under this Regulation. In the absence of guiding precedent, the writer would err on the side of caution, and suggest that any form of suicidality should be regarded as a SAE, and should be reported, as such.

On this basis, the sponsor should have informed the regulator of those SAEs, and would be liable, had it failed to do so. Assuming that the trials have been conducted outside the EU, liability would accrue to the sponsor, where it had failed to enter SAEs on the European database, under Regulation 34. It would also be liable under Regulation 35, in the event that it had failed to submit an annual SAE report, and/or a safety report for all trialists affected.

Next, there appears to be an issue over the application of Regulation 50, which concerns the provision of false, or misleading information, where such provision impacts upon the assessment of safety and efficacy. It is unclear from the facts, as presented, to establish whether or not the sponsor, or any of its agents, provided the UK regulator with false information. There appears to be a question as to how the information that was given was interpreted, at least publicly, with Advanced Bromide initially accepting the unsatisfactory nature of the trials and deciding against a licence application, although it then appears to change its mind, and by some mechanism, which is unclear from the facts, Dave, Edwina, Fatima and Jake arrive at a conclusion that appears to be very nearly diametrically opposed to that that Advanced Bromide reached.

Nevertheless, it is not clear from this that Advanced Bromide did other than interpret the statistics at its disposal in its favour, whereas an alternative reading would permit a disinterested party to reach the same conclusion that the Company did, originally. As such, unless the Company not only provided Jake's publication to the regulator, but also provided raw data (or statistical summary) that had been edited to exclude or diminish evidence of SAEs, then it is difficult to establish liability under Regulation 50, on the basis of the publication, alone.

However, the writer respectfully observes that he believes there to be a grey area, here. And this is that the Regulations do not provide for data withheld, which might impact on the assessment of safety and/or efficacy in a drug. According to the facts of the case, Advanced Bromide carried out more than one trial, and yet it seems that the results of only one trial were published. We are not advised as to whether the data from these other trial(s) were provided to the regulator, and it is not clear that it is an offence even if they were not.

In the absence of caselaw, the writer is obliged to argue that a failure to communicate adverse data from a "failed" trial amounts to providing false or misleading information, although it is by no means the natural meaning of those words. It is evidently the intention of Parliament to establish a system of legislation, which permits the regulator with the best possible opportunity to properly assess a drug for licensing. Any conduct that undermines that effort is going against the spirit of the legislation, I would argue. Moreover, given that withholding trials data is viewed as both unscientific and potentially detrimental to the public, it cannot have been Parliament's intention to permit this loophole to remain, even for the purpose of protecting information proprietary to pharmaceutical companies. Viewed from a wider perspective, then, the provision to the regulator of no more than half of the available data amounts to an attempt to mislead, in the writer's opinion. The trial that was published, then, should not be viewed in isolation, and should be seen merely as part of the information, which Regulation 50 requires to be made available. As such, if Advanced Bromide has withheld the (even) less favourable data from its other trial(s) it is suggested that this amounts to an offence under Regulation 50.

Furthermore, given that there seems to be a suggestion that the Company chose to represent the data other than in accordance with its belief that the trial had not been successful, there may be liability for fraud, here. Given that the mechanism is missing from the facts set down, which led to the Company deciding to press ahead with a licence for minors in the face of its initial judgement, it is difficult to come to a definitive conclusion on this, particularly if Dave, Edwina, Fatima and Jake are determined that their interpretation of the data was good, despite the side effects. The facts, as presented, do not indicate either way whether there was an instruction to Dave from a superior. As such, one might deduce that he was acting on his own volition, but even this is unclear.

Without the benefit of the raw data, it is not possible to establish whether Edwina misrepresented this, when rendering those data into the "manageable format" that it is assumed was presented to Fatima. Nor, from the facts, is it clear that Fatima has done other than write up a report in accordance with the data that was presented to her, although there remains a question over the instructions that Dave gave to Fatima, as to the form that those instructions took. If Dave was deliberately attempting to mislead, then it is not clear what his motive was for doing this: there is certainly no mention of any financial advantage accruing to him, which would be a requirement of any liability for fraud.

If Fatima has acted in bone fide, then Good Healthy will presumably avoid vicarious liability for any civil action. There is no evidence presented in the facts to suggest that Good Healthy was involved in any attempt to mislead the regulator, and as such it appears not to have any liability under Regulation 50. Finally, Jake and his colleagues, one step further removed from the process, may not have acted with complete propriety, given that they put their names to a piece of work that was not theirs, solely for the purpose of increasing the profile of the report, when it was published. However, there is no evidence that Jake's actions misled the regulator.

Matthew Holford (c) 2007