Given the significant expense associated with clinical trials, it is not surprising that pharma companies will look for redress in the event that the clinical trial does not yield sufficiently positive results and the work of clinical research organisations will come under scrutiny.
In the recent case of Cardiorentis AG v IQVIA Limited and another  EWHC 250 (Comm) (available here), the High Court was asked to consider, for the first time in an English Court, the duties of the parties involved in a clinical trial and the standard of care required by clinical research organisations. The case provides a warning that even though breach of an obligation might be established, that breach has to be shown to cause the loss claimed.
Cardiorentis AG, a research-focused pharmaceutical company, engaged IQVIA, a major contract research organisation (“CRO”) to conduct a phase III clinical trial to evaluate the safety of a drug called “Ularitide” in patients with acute heart failure. Unfortunately, the results of the clinical trial did not indicate improved patient outcomes in those receiving Ularitide and Cardiorentis considered that IQVIA were to blame.
Cardiorentis issued proceedings against IQVIA arguing that IQVIA had breached the terms of the General Services Agreement (“GSA”), being the main contractual agreement governing the relationship of the parties. In particular, it was alleged that IQVIA failed to provide the services with the standard of care customary in the contract research organisation industry (under the express term in the GSA) and/or with reasonable care under the implied term pursuant to section 13 of the Supply of Goods and Services Act. More specifically, Cardiorentis alleged that (among other things) IQVIA:
- Failed to provide any adequate training or monitoring by IQVIA medical advisors, particularly with respect to compliance with eligibility and entry criteria;
- Failed to train investigators to ensure that the trial was conducted in accordance with the protocol; and
- Failed to report protocol deviations to Cardiorentis in any appropriate, clear or timely manner (in particular, instances of breach of the eligibility and entry criteria).
As a result of these failures, Cardiorentis argued that a significant number of ineligible subjects were included in the trial, causing the trial data to be unreliable. As to its loss, Cardiorentis pleaded that by virtue of IQVIA’s alleged failures, it was deprived of the opportunity to earn revenue on the development of Ularitide. Alternatively, Cardiorentis sought to recover its wasted expenditure on the clinical trial.
IQVIA denied that it had failed to meet the required standard of care in its performance of the services under the GSA and counterclaimed for its unpaid invoices.
Butcher J, giving the leading judgment, held that the contractual standard to which the services were to be provided in this case (being those customary in the CRO industry) was no lower than the standard of reasonable skill and care implied by the Supply of Goods and Services Act 1982. Notwithstanding this, Butcher J found that Cardiorentis had not succeeded in showing that any identifiable or significant number of eligibility Protocol deviations were the result of IQVIA’s breach of contract. While there were some limited areas in which breach was established, most of Cardiorentis’s allegations of breaches which caused there to have been the enrolment of subjects with eligibility or other protocol deviations were not made out.
As to causation, Butcher J found that even if there were eligibility or other protocol deviations which were IQVIA’s fault, Cardiorentis had not been able to show that these deviations had any adverse affect on the clinical trial. He went on to say 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”.
In coming to his decision on causation, and of real practical relevance to pharma companies, the Judge noted that:
- Cardiorentis had not contracted for the conduct of a study which produced a particular result. It had contracted instead for the conduct of a study which produced a meaningful and interpretable result, positive or negative, as far as the efficacy of the drug was concerned;
- Some eligibility and other protocol deviations were to be expected in any study; and
- There was no recognised threshold or cut off in the number or percentage of eligibility or other protocol deviations which would mean that regulators or the scientific community would consider the study unreliable.
In relation to the wasted expenditure claim, Butcher J emphasised that a claimant cannot show that expenditure has been wasted to the extent that it has received benefit. He noted that the results of the clinical trial were “reliably negative” and amounted to an accurate reflection of the effect of the drug on the population tested. Furthermore, those results were such as to have satisfied the scientific community as to the effectiveness or otherwise of Ularitide in a population such as the one tested. In those circumstances, it was held that the expenditure on the clinical trial was not wasted.
In light of the above, the High Court dismissed Cardiorentis’ claim for damages and wasted expenditure. Butcher J concluded that IQVIA was entitled to succeed in relation to its counterclaim for invoices rendered in an amount of EUR4,509,244.47.
The case shows the difficulties which can arise in challenging the performance of a clinical trial. Even though breaches of contractual obligations were established, those breaches were not held to be causative of the damages and loss claimed. The decision makes it clear that even if protocol deviations and mistakes occur in clinical trials, these will not necessarily amount to a breach of duty/standard of care and that even if they do, the breach may not have any adverse causative effect on the outcome of the trial.