A few weeks ago, I was contacted by a journalist writing up a news item for Nature Medicine on the drift in the UK’s competitiveness in clinical research, and the measures being taken to address it. I wrote a response, which I knew was far too long.
This morning, I read the news item as it made it to print in the February issue of Nature Medicine (http://www.nature.com/nm/journal/v16/n2/full/nm0210-134b.html). I knew that my comment was far too long for its subtleties to make it through into the printed version, but it might be useful to publish here the full text of what I said…
It is undeniable that the UK now provides a smaller proportion of patients to clinical trials than was the case a decade ago. To ascribe this to internal changes, though, oversimplifies the issue. The efforts to streamline clinical trial authorisation, start-up etc. have been successful, in that without them the impact of external factors would have been even greater.
Over the past decade, many additional countries (particularly the BRIC countries, Brazil, Russia, India and China) have entered the marketplace as locations for clinical trials, offering access to patients at a numerical scale, rate of randomisation and cost-per-patient that mature markets could not hope to match. Cost advantages are decreasing as these countries develop, but demographic advantages remain.
At the same time, standards of conduct have been raised, with the aim of increasing protection of clinical trial participants. Key developments have included the ICH Good Clinical Practice guideline (1997), the EU Clinical Trials Directive (2001, implemented 2004) and the various versions of the Declaration of Helsinki (most recently in 2008). In the UK, public concern following scandals such as Alder Hay also raised the priority of research governance for the Department of Health and NHS Trusts. These developments have made it much harder to conduct poor quality research, a publicly desirable outcome, albeit with increased administrative costs and (more importantly for clinical trials of patented products) timelines.
These factors, one an inevitable consequence of globalisation and the other clearly desirable, have impaired competitiveness in the UK and indeed throughout the developed world.
There is also a demographic aspect: clinical trials collect evidence that is hoped to demonstrate that a product will be effective in a given patient population, but also in the specific healthcare delivery regimen and socio-economic setting of its intended market. Drugs entering clinical development now could hope to receive regulatory approval in the early 2020s, by which time the increasingly numerous and affluent middle classes in the BRIC countries and beyond could comprise a market of equal or greater value to traditional markets in the “developed world”. If their economic development continues, conducting clinical research in these countries there will become more important regardless of any improvement in productivity in the UK, other EU countries etc.
All of these issues are having an impact on inward investment to conduct clinical research in the UK. With investigational sites in all countries competing to recruit the total number of participants required for a study, slow sites in the UK can lose out to quicker sites elsewhere, with payment following patients. In addition, some pharmaceutical companies and contract research organisations (CROs) are compiling lists of “preferred” countries in which to concentrate their research activities, mainly based on prior performance, and the UK is not always on these lists.
However, much has been done to address this. Common systems to submit study protocols for regulatory and ethics approval, guidelines to improve transparency and consistency of study costs, standardised contract terms, coordinated networks to share expertise and resources, and enhanced infrastructure and structured development and training for clinical research professionals are all having an impact. Implicit in this is the acknowledgement that there are certain therapeutic areas and types of clinical trial where UK sites do still perform well and add value, and it is in these areas where future efforts and investment should be concentrated.
There are still improvements to be made, and the next wave of initiatives were set out last summer in the Office of Life Sciences’ Blueprint. In addition, a process to review the EU Clinical Trials Directive has just begun, with a view to increasing harmonisation of regulation across the EU and reducing the administrative burden of compliance, without sacrificing protection of study participants.
It would be unrealistic to expect the UK to have maintained pre-2000 levels of competitiveness in the face of such strong external factors. Efforts are continuing with the aim of improving absolute performance, but the societal value of improved participant protection should not be understated. The UK should continue to focus its efforts on therapeutic areas and types of study where it performs best and adds most value.
In the first round of feedback with the journalist, I picked up on the aspects that he found most useful, and wrote a couple of summaries on those areas:
- “Like the rest of the economy, clinical research has globalised in the past decade, with rapid access to high numbers of patients now possible in countries that saw virtually no clinical research 15 years ago,” says Andrew Smith, editor of Clinical Research focus, published by the Institute of Clinical Research. “UK initiatives have succeeded in partially offsetting this, but when more competitors enter a market the leaders’ performance tends to be diluted.”
- The conduct of trials was also tightened up by international initiatives such as the ICH Good Clinical Practice guidelines and EU Clinical Trials Directive. The implementation of these into law, in the UK and elsewhere, have increased the administrative burden of clinical trials but have “made it much harder to get away with conducting poor quality research, which is a publicly desirable outcome,” Smith says. Current initiatives are trying to make compliance less costly without compromising patient protection.
I wouldn’t want my publication of this to be seen as criticism of the reporter or his editor, but I would like to get the finer detail of my points “out there”, so readers don’t misunderstand the balance of my views on clinical research in the UK, its recent difficulties, and the efforts that are being made against strong economic forces.
