On 30 October 2006 the Department of Health, in partnership with the NHS, the Association of British Pharmaceuticals Industry (ABPI) and the BioIndustry Association (BIA), released a revised model Clinical Trials Agreement (mCTA). The revised mCTA is designed to speed up the contracting process and ensure early initialisation of research.
The mCTA was originally launched in 2003 by the DofH and the ABPI. It was intended for use in industry sponsored clinical trials in patients in NHS hospitals throughout the UK. The mCTA is not intended to cover collaborative research between industry and academia. It also specifically excludes research involving healthy volunteers.
The revised model contains modified provisions relating to trust liabilities, industry arrangements, intellectual property and dispute resolution and includes updates to reflect:
- Lessons learnt from the implementation of the older version;
- NHS organisational changes;
- Updates to legislation and research governance obligations; and
- Undertakings by industry to register trials and publish results.
The revised mCTA also includes a number of additional and revised definitions of commonly used terms within the agreement.
We have set out below some of the key changes made to the revised mCTA.
The revised mCTA makes a marked departure from its earlier stance in relation to the protocol outlining arrangements for trials across all countries and sites. Previously where any provisions of the mCTA conflicted with the protocol, the terms of the protocol would prevail. However under the new mCTA, the position has changed slightly. Now, where there is a conflict in relation to clauses dealing with liabilities/indemnities, confidentiality, data protection, freedom of information, publication or intellectual property, the terms of the mCTA will prevail.
The revised mCTA no longer makes any reference to foreign laws. This change means that sponsors must notify hospitals of any specific requirements related to performance of trials that arise under foreign laws.
Obligations of the parties
The mCTA is designed to facilitate trial initiation, however delays often occur in getting the necessary regulatory approval for these trials. It has previously been noted that there are advantages to signing off mCTA agreements before such approval is obtained however these advantages need to be balanced with the danger of beginning the actual trials before authorisation is secured. Therefore under the new mCTA, the sponsor may not supply the Investigational Medicinal Product (IMP) to the trial site until it has all the necessary approvals, allowing the correct balance to be achieved.
Due to the removal of reference to foreign laws, the sponsor must, under the revised mCTA, specify to the investigator exactly what financial disclosures are necessary (i.e. where disclosures are required under the FDA rules).
In respect of the trial subjects, previously, issues have arisen in obtaining the required number. Under the new mCTA, hospitals are required to use their ‘best endeavours” to fulfil the recruitment target, however the new mCTA now provides some flexibility in the number of subjects to be obtained. If it does not appear that the required number is going to be met, then the revised mCTA permits the trial to be scaled back. Conversely, the trial may be expanded where participants are recruited more easily than anticipated.
In addition to the above, the revised mCTA outlines various provisions relating to access, research misconduct and regulatory authorities, including various reporting requirements. Most notably the revised agreement does not require the sponsor to report to the hospital on trial progress, nor does it require them or the hospital’s R&D director to review the site’s performance at the end of the trial.
Liabilities and Indemnities
The revised mCTA has imposed caps on a hospital’s liability to the sponsor. The caps are set at two levels depending on the nature of the breach. Liability for wilful and/or deliberate breaches of the agreement or breaches related to confidentiality, data protection and freedom of information, publication and/or intellectual property will be capped at twice the value of the contract. Liability for all other breaches committed by the hospital will be capped at contract value.
Freedom of information
The revised mCTA includes provisions relating to the disclosure of information related to contract clinical trials. Newly negotiated obligations ensure that hospitals will take timely actions to inform the sponsor of any requests for information, consult with the sponsors about disclosing such information and inform them of any plans to disclose such information against the sponsor’s wishes.
The revised mCTA has included newly agreed IP clauses designed to protect the sponsor’s IP and give them ownership of any trial derived IP and know how, whilst allowing the site to exploit clinical procedures or related improvements attained during the course of the trial. The new provisions set out the following main principles:
- That each party is to retain ownership of any IP or know how owned or licensed before the agreement came into effect;
- Any IP or know how generated at the trial site that is related to the clinical trial, the IMP or the protocol (excluding any clinical procedures or related improvements) is the property of the sponsor;
- Such clinical procedures or related improvements at the trial site can be protected and exploited (depending on the inventor’s employer (i.e. hospital or university);
- The site of the trial has the right to use any know how obtained during the trials in it normal clinical work.
As per the original mCTA, the parties are required, in the first instance, to attempt to solve any dispute through mediation. The revised mCTA has gone further by setting out a local procedure for mediation, increasing in formality where necessary. If the parties fail to mediate, the revised mCTA provides that either party may take the dispute to the courts in the jurisdiction in which the trial site is located.
It is important to note that the mCTA only applies to investigational medicinal products and biologicals and does not apply to medical devices. The same working group is preparing a separate model agreement in respect of investigations involving medical devices, which is expected to be published early in 2007.