Most life sciences organisations will utilise a CRO (contract research organisation) at some stage of their product development lifecycle, whether for a new drug or a medical device. This ruling shines some light on how contractual documentation and industry standards of practice will be interpreted by the English courts.
The case also importantly clarifies the sponsor’s ownership of clinical trial data and the documents within the electronic trial master file (eTMF), and whether a CRO can withhold access to data or the eTMF in a dispute over payment.
In this article, partner Dr Lisa Page, a former project manager of clinical trials for Quintiles (now IQVIA), evaluates how the English High Court analysed these contracts and determined the standard of care required between a CRO and the sponsor for the provision of clinical trial management services, and provides practical tips on how to address the issues raised.
Cardiorentis AG, a pharmaceutical company, instructed a well-known CRO, IQVIA, to carry out a clinical trial evaluating the safety of a drug called ‘Ularitide’ in patients who had acute heart failure. The trial results showed that this drug did not improve the patients’ medical condition, and it was the position of Cardiorentis that this was the fault of IQVIA’s management of the trial.
Cardiorentis issued proceedings against IQVIA, arguing that:
- IQVIA breached the terms of the general services agreement (GSA), alleging that IQVIA failed to meet the required standard of care expected of a CRO;
- IQVIA did not provide adequate training to trial staff, specifically in terms of compliance with eligibility and entry criteria; and
- IQVIA did not report deviations in entry and eligibility criteria to Cardiorentis appropriately, clearly or in a timely manner.
In light of the above, Cardiorentis argued that the large number of ineligible patients enrolled (358 of the 2157 patients) was due to IQVIA’s failings, and therefore the trial data was unreliable.
Cardiorentis went on to plead that its outgoings on the clinical trial were wasted costs as the failure of the trial was due to breaches by IQVIA.
IQVIA counterclaimed for unpaid invoices, denying it had failed to meet the required standard of care under the GSA.
Cardiorentis also claimed an injunction for delivery up of the trial data and the eTMF, stating that the contractual documents made it clear that it owned the trial data and the information in the eTMF, and regulatory requirements meant that, as the sponsor, it should at all times have access to that data to fulfil its regulatory responsibilities.
The case was heard in the High Court by Mr Justice Butcher, who held that:
- Cardiorentis failed to demonstrate any significant breaches on behalf of IQVIA in terms of eligibility of trial participants. While there were some limited breaches by IQVIA, Cardiorentis had failed to demonstrate that these deviations had any adverse effect on the negative results of the trial; and
- the results provided sufficient evidence to satisfy the scientific community as to the effectiveness and/or safety of the drug in question. The judge stated that: “the study was still a robust and interpretable study, albeit one which was negative as far as the efficacy of the drug was concerned”, and therefore the claim for wasted costs failed.
The judge then made the following points on the function of CRO contracts:
- the parties had not entered into a contract where the clinical trial was to produce a specific result, but had entered into a contract for IQVIA to conduct a study producing a ‘meaningful and interpretable result’ in relation to the efficacy of the drug, whatever that result may be;
- eligibility and other protocol deviations are to be expected in any clinical trial and do not necessarily mean that there were issues with the CRO’s management of the trial;
- the standard of care required by IQVIA as set out in the contractual documents was that which is ‘customary in the contract research industry’. The judge held that the associated documents such as the quality management plan, the protocol deviation management plan and the monitoring guidelines served to illustrate the standard of care but were not contractually binding; and
- The GSA had not specified any contractual timeframe for 100% source data verification which meant that issues with eligibility of patients may not have been identified quickly.
In relation to Cardiorentis’ outgoings or ‘wasted expenditure’ claim, the judge noted that a claimant cannot show that expenditure has been wasted to the extent that it has received benefit. As the results of the clinical trial were ‘reliably negative’, giving an accurate reflection of the drug’s efficacy on the trial participants, the trial was successful despite the negative result. Therefore, it was held that Cardiorentis’ outgoings on the clinical trial were not wasted.
Importantly for sponsors, the judge found in Cardiorentis’ favour in granting an injunction for IQVIA to allow Cardiorentis access to the clinical trial data and the eTMF irrespective of payment of invoices.
IQVIA’s counterclaim was successful, with Cardiorentis being ordered to pay IQVIA €4.5 million in respect of unpaid invoices for its services in relation to the clinical trial.
Clinical trials are hugely expensive, and sponsors often contract CROs to manage their clinical trials with many obligations delegated. It comes as no surprise that sponsors may try to seek compensation when a clinical trial does not produce positive results and the services provided by the CRO in question will be examined.
This case highlights how difficult it can be to challenge the performance of a clinical trial, as even where contractual breaches by a CRO are established, those breaches may not be the cause of any failure of the trial and therefore the CRO will not have any liability for damages and losses claimed by a sponsor.
To try to address this issue we recommend that all sponsors ensure that the following issues are addressed in their CRO contracts:
- The standard of care expected from the CRO is dealt with more specifically in contracts with the contract referencing, for example, the CRO’s standard operating procedures.
- The terms and obligations of the CRO under the quality management plan or protocol deviation management plan are expressly incorporated as contractual obligations rather than standards of care.
- Requirements for source data verification (SDV), especially with regards to checking patient eligibility criteria, are set out in detail including the percentage level of SDV as well as the timeframe for its completion.