Michael McGuinness left TMQA last week to start his career at the MHRA. We are delighted that the experience Michael has gained with TMQA over the last 5 years has enabled him to take up this prestigious position. We all miss working with Michael and wish him all the best in his new role.
HRA Announces Start Date for Phased Roll-out of HRA Approval
The Health Research Authority (HRA) will begin the roll-out of the new HRA Approval process on 11 May 2015. HRA Approval is the new process that will be required before research can commence in the NHS in England. It will replace the current local Research & Development (R&D) approval process and will remove the need for NHS permission to be granted by each participating organisation. The new HRA Approval process will comprise a review by a Research Ethics Committee as well as an assessment of regulatory compliance and related matters undertaken by dedicated HRA staff. The new system will simplify the approval process for research, making it easier for research studies to be set-up. It will eliminate duplicate application routes and will remove duplication of reviews of research by NHS support teams. There will be a phased roll out of this new HRA Approval process by study type, starting with studies that fall into Cohort 1 (details of the different types of studies that fall into each cohort can be found on the HRA website). The timing of the next roll out phase will be announced once the HRA has reviewed the implementation of the first phase.
Mandatory Use of eCTD for Decentralised Procedures
From 01 July 2015, new marketing authorisation applications for decentralised procedures must be submitted in electronic common technical document (eCTD) format. Marketing authorisation applications submitted to the MHRA in non-eCTD format will be rejected. Around 90% of new applications for decentralised procedures received by MHRA are already submitted in eCTD format. New marketing authorisation applications in mutually recognised procedures will still be accepted in both non-eCTD and eCTD formats, however applicants are encouraged to use eCTD format wherever possible as the use of the non-eCTD submission formats for these applications is planned to be phased out by 1 Jan 2017.
The decentralised and mutual recognition procedures are European marketing authorisation procedures which are based on the principle of recognition of the assessment by a Reference Member State. The decentralised procedure is used to obtain a marketing authorisation in several EU Member States when the applicant does not yet have a marketing authorisation in any country. The applicant requests one country to be the Reference Member State (RMS). The RMS circulates its draft assessment report to the other concerned Member States and the applicant for comment. In the mutual recognition procedure, a marketing authorisation has already been issued by the RMS and the RMS’s assessment report forms the basis for requesting other Member States’ mutual recognition of the marketing authorisation, unless they have objections on the grounds of a potentially serious risk to public health, in which case further discussions would be held in the Coordination group for Mutual recognition and Decentralised procedures (CMDh).
WHO Calls for Increased Transparency in Clinical Research
The World Health Organisation (WHO) issued a public statement this month calling for the disclosure of results of clinical trials of medicinal products, whatever the result. Dr Marie-Paule Kieny, WHO Assistant Director General for Health Systems and Innovation stated “It underpins the principal goal of medical research: to serve the betterment of humanity. Failure to publicly disclose trial results engenders misinformation, leading to skewed priorities for both R&D and public health interventions”. In a study that analysed reporting from large clinical trials (more than 500 participants) registered on clinicaltrials.gov and completed by 2009, 23% had no results reported. These unreported trials included nearly 300,000 participants. In 2005, the WHO called for all clinical trials to be registered and this led to the establishment of the International Clinical Trials Registry Platform, which collates information on clinical trials that have been notified in a network of clinical trial registries such as the EU Clinical Trials Register.
The new EU Clinical Trials Regulation No. 536/2014, which was passed in April 2014, requires drug makers to publish clinical trial results. The European Medicines Agency (EMA) already hosts a trial database – the EU Clinical Trials Register – however, it has not yet decided how the additional information required by the new Clinical Trials Regulation will be made public.
Draft FDA Guidance on Acceptance of Foreign Medical Device Clinical Data
The US Food and Drug Administration (FDA) issued a draft guidance for industry this month entitled ‘Acceptance of Medical Device Clinical Data from Studies Conducted Outside the United States’. The draft guidance expresses the FDA’s policy of accepting scientifically valid clinical data from foreign clinical studies in support of premarket submissions for devices. The guidance describes special considerations that apply when relying on clinical data from foreign studies. These include:
- Differences in clinical conditions – countries outside of the US may have different standards of care which may affect the analysis of the benefits and risks of the studied device relative to standard practice. Differences in clinical facilities and levels of clinical skill can also affect study data from outside the US to the extent that such data may not be generalised to US clinical practice and the differences could impact the data’s usefulness in supporting the safety and/or effectiveness of the device.
- Differences in study populations – differences in the race, ethnicity, age and gender of a foreign population can affect the applicability of the study to the intended US population. The foreign studied population and the intended US patient populations may also differ in the prevalence of confounding clinical factors that can affect risks of an intervention as well as clinical response. For example, populations vary widely in the prevalence of smoking, diabetes and obesity, and rare or regionalised co-morbidities occur in certain populations that can confound study results.
- Differences in regulatory requirements – when studies conducted outside the US are initiated to satisfy the requirements of foreign countries, rather than, or in addition to FDA the studies may not be designed to address the questions necessary to satisfy FDA requirements.
Valid scientific evidence is only one factor in determining whether FDA can use the data to support a decision on premarket submission but does not generally address ethical considerations. In 2013, FDA proposed a rule – ‘Human Subject Protection: Acceptance of Data from Clinical Studies for Medical Devices’ – which requires that clinical studies conducted outside the US in support for premarket submissions be conducted in accordance with good clinical practice. The proposed rule, when finalised, is intended to help ensure the protection of human subjects and the quality and integrity of the data obtained from these studies.