The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has launched a public consultation on proposed amendments to the Medicines for Human Use (Clinical Trials) Regulations 2004.
The changes put forward in consultation document MLX 340 address three unrelated topics falling under the remit of the clinical trial regulations, which implemented the Clinical Trials Directive (2001/20/EC) as well as aspects of other European Union directives. They deal with emergency care research in children, the role of the UK’s Gene Therapy Advisory Committee (GTAC) and the membership and operation of UK ethics committees.
In the first case, the amending regulations would allow trials of emergency care medicines in children without initial informed consent. Article 3 of the Clinical Trials Directive includes a general requirement that all trial subjects – or their ‘legal representative’, if they are unable to give informed consent – must consent in advance to participation in a clinical study. Article 4 of the Directive repeats this requirement where it applies to minors, so that consent must be obtained from parents or a legal representative.
Last year, and after wide consultation with representatives of clinical trial sponsors, the UK modified the requirement that informed consent must be obtained from the legal representative of an incapacitated adult prior to participation in a study involving administration of medicines under emergency circumstances, the MHRA noted. The application of the associated information requirements was also modified.
A number of respondents to this consultation argued that the amendments should also apply to clinical trials with minors where urgent action was required. Independent expert groups on paediatrics and medicines have agreed, subject to there being approval by an appropriate ethics committee of the protocol describing the proposed procedure for including trial participants.
In addition, the MHRA pointed out, a new EU guideline on the ethics of children participating in clinical trials, currently being finalised by the European Commission, states under the heading of ‘Informed consent in emergency trials’: “As for non-emergency situations, however, it would be unethical to deny children the benefit of research in these situations. In these situations, consent should be obtained according to national law.”
One of the conditions for the emergency-care research exception for adults introduced by last year’s UK amendments is that is not reasonably practicable to obtain informed consent. As soon as this condition is no longer met, the legislation requires that consent is obtained as the exemption becomes invalid and the normal consent provisions in the regulations apply.
A parallel safeguard is envisaged in the amendments for emergency care research in children, along with the requirement that an independent ethics committee must give prior approval of the detailed circumstances in which the exception is to be used.
The proposed amendments to the role of the Gene Therapy Advisory Committee under the clinical trial regulations would “allow the committee to more effectively focus on novel, challenging approaches, thereby enabling it to continue its important function as a ministerial advisory body for gene therapy research”, the MHRA explained.
This would include clarifying which applications for clinical studies should be submitted for GTAC review by excluding genetically modified (GM) vaccines for infectious disease, as “these could be adequately considered by other recognised Research Ethics Committees (RECs)”. GM vaccines for infectious diseases are not usually understood to be gene therapy products but the EU’s definition is ambiguous in this respect, the MHRA comments.
It proposes that the GTAC should have the power to delegate routine gene therapy applications to another recognised REC. Clinical experience with some gene therapies is becoming routine because of technical advances in the field, the MHRA says.
A number of “practical issues and anomalies” have arisen in the implementation of the clinical trial regulations with respect to the membership and operation of ethics committees, the agency notes.
The amendments proposed in MLX 340 – for example, removing certain restrictions on membership arising from the definitions of expert and lay members in Schedule 2 of the regulations – are intended to address these difficulties while providing more flexibility to ethics committees and their appointing authorities.
The deadline for comments on MLX 340 is 7 December 2007.