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SIOPE proposes amendments for EU clinical trial regulations
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Geoff Tompkinson/SPL
SIOPE proposes amendments for EU clinical trial regulations
Published Online March 1, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70064-0 For more about the SIOPE meeting see http://www.siope. eu/SIOPE-EU/English/HomePage/Conferences-Events/ International-Childhood-CancerDay-2013/page.aspx/329 For the Clinical Trials Regulation see http://ec.europa.eu/health/ files/clinicaltrials/2012_07/ proposal/2012_07_proposal_ en.pdf For the Clinical Trials Directive 2001/20/EC see http://eur-lex. europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2001:121 :0034:0044:EN:PDF For SIOPE’s proposed amendments for the EU Clinical Trials Regulation see http:// www.siope.eu/binarydata. aspx?type=doc/SIOPE_Board_ Amendments.pdf
282
Feb 15, 2013, was International Childhood Cancer Awareness Day, and on Feb 20, 2013, the European Society of Paediatric Oncology (SIOPE) held its yearly high-level meeting at the European Parliament (Brussels, Belgium) to mark this occasion. The focus of the meeting was the proposal by the European Commission (EC) for the European Union (EU) Clinical Trials Regulation (CTR), which is being assessed by the member states and European Parliament. Once passed, the CTR will replace the tight but disproportionately regulated and much-criticised EU Clinical Trials Directive 2001/20/EC (Directive). In the EU, the number of applications to undertake clinical trials fell from 5000 in 2007 to 3800 in 2011. For non-commercial sponsors, the administrative costs have risen by 98%, and for industry sponsors, insurance fees have increased by 800%. Of the 93 articles in the CTR, two might have major effects on the undertaking of clinical trials: a “lowintervention clinical trial” category and the requirement for a national indemnification mechanism. A low-intervention clinical trial is one that poses only a minimum risk to the safety of participants versus standard clinical practice. It is important for the optimisation of the use of the medicinal product or intervention. Although SIOPE supports the CTR, and particularly the idea of a low-intervention clinical trial category, it proposed some amendments for further clarification—eg, that Article 2 part 2b (definition of a clinical trial) should not apply to studies in which data are being gathered for the standard offlabel use of medicinal products. Many people support the amendments proposed by SIOPE. According to Richard Sullivan (Kings Health Partners Integrated Cancer Centre, Guy’s Hospital, London,
UK), “The Directive has been one of Europe’s worst own goals. The amendments proposed by SIOPE are essential for conducting clinical trials in children with cancer, nearly all of which are investigator driven with little support from industry”. He added that “There remains a clear need to substantially revise the Directive and for Europe to continue to support trans-boundary research and development in cancer”. Neena Modi (Imperial College London, London, UK) also welcomes SIOPE’s recommendations and believes that they are timely: “SIOPE advises extending the concept of lowintervention clinical trials that attract a reduced regulatory requirement to those involving standard treatments. However, what is considered a standard treatment may vary widely between clinicians, no less than between countries, and SIOPE have wisely advised that careful thought is given to the definition.” According to SIOPE president Gilles Vassal (Institut Gustave-Roussy, Villejuif, France) and SIOPE board member Pamela Kearns (University of Birmingham, Birmingham, UK), “The EC have clearly accepted the criticisms levelled against the Directive, notably the negative impact the Directive had on non-commercial trials and have introduced measures to facilitate academic trials through proportionate regulation”. Vassal and Kearns believe that the introduction of the low-intervention trial category is a huge step towards proportionate regulation, particularly with respect to most paediatric oncology trials in which the aim is to optimise the use of currently available licensed drugs. Another notable principle in the CTR is the requirement for a national indemnification mechanism. According to Vassal and Kearns, “The current requirement for a trial sponsor to provide insurance cover for clinical trials has impeded
progress in international academic collaborations due to the prohibitive insurance premiums that are disproportionate to the insured risk. Although there may be reluctance from member states to adopt national insurance schemes, due to an unfounded perception of high costs, we strongly urge the European Parliament to ensure they are mandated.” Carmen Bell (Insurance Europe, Brussels, Belgium) offers a solution in the form of a voluntary insurance system to enable insurers and their customers to negotiate more freely and enhance the insurer’s ability to design suitable cover at economically practicable costs. “This voluntary system would be most beneficial, however, if applied to all clinical trials, regardless of the level of intervention”, she said. Adam Cohen (Centre for Human Drug Research, Leiden, Netherlands), however, has reservations about the EC’s proposal for the CTR, explaining that “SIOPE’s comments are an example of the many thoughtful remarks that are made about the details of the new CTR throughout Europe. Until now the EC has shown very little flexibility in moving from the original text, so I am not hopeful this work will pay off. Much more important is that the basic and serious flaws in the CTR are not addressed. The illogical dual approach of approval with one country and many ethics committees will make the system crash. Also the system of approval by single member states without a central quality institution that guards that the differences in quality of science between member states will not lead to dangerous situations is a serious liability. We need to be concerned that the CTR does not go the way of the euro through lack of centralised control.”
Farhat Yaqub www.thelancet.com/oncology Vol 14 April 2013
Geoff Tompkinson/SPL
SIOPE proposes amendments for EU clinical trial regulations
Published Online March 1, 2013 http://dx.doi.org/10.1016/ S1470-2045(13)70064-0 For more about the SIOPE meeting see http://www.siope. eu/SIOPE-EU/English/HomePage/Conferences-Events/ International-Childhood-CancerDay-2013/page.aspx/329 For the Clinical Trials Regulation see http://ec.europa.eu/health/ files/clinicaltrials/2012_07/ proposal/2012_07_proposal_ en.pdf For the Clinical Trials Directive 2001/20/EC see http://eur-lex. europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2001:121 :0034:0044:EN:PDF For SIOPE’s proposed amendments for the EU Clinical Trials Regulation see http:// www.siope.eu/binarydata. aspx?type=doc/SIOPE_Board_ Amendments.pdf
282
Feb 15, 2013, was International Childhood Cancer Awareness Day, and on Feb 20, 2013, the European Society of Paediatric Oncology (SIOPE) held its yearly high-level meeting at the European Parliament (Brussels, Belgium) to mark this occasion. The focus of the meeting was the proposal by the European Commission (EC) for the European Union (EU) Clinical Trials Regulation (CTR), which is being assessed by the member states and European Parliament. Once passed, the CTR will replace the tight but disproportionately regulated and much-criticised EU Clinical Trials Directive 2001/20/EC (Directive). In the EU, the number of applications to undertake clinical trials fell from 5000 in 2007 to 3800 in 2011. For non-commercial sponsors, the administrative costs have risen by 98%, and for industry sponsors, insurance fees have increased by 800%. Of the 93 articles in the CTR, two might have major effects on the undertaking of clinical trials: a “lowintervention clinical trial” category and the requirement for a national indemnification mechanism. A low-intervention clinical trial is one that poses only a minimum risk to the safety of participants versus standard clinical practice. It is important for the optimisation of the use of the medicinal product or intervention. Although SIOPE supports the CTR, and particularly the idea of a low-intervention clinical trial category, it proposed some amendments for further clarification—eg, that Article 2 part 2b (definition of a clinical trial) should not apply to studies in which data are being gathered for the standard offlabel use of medicinal products. Many people support the amendments proposed by SIOPE. According to Richard Sullivan (Kings Health Partners Integrated Cancer Centre, Guy’s Hospital, London,
UK), “The Directive has been one of Europe’s worst own goals. The amendments proposed by SIOPE are essential for conducting clinical trials in children with cancer, nearly all of which are investigator driven with little support from industry”. He added that “There remains a clear need to substantially revise the Directive and for Europe to continue to support trans-boundary research and development in cancer”. Neena Modi (Imperial College London, London, UK) also welcomes SIOPE’s recommendations and believes that they are timely: “SIOPE advises extending the concept of lowintervention clinical trials that attract a reduced regulatory requirement to those involving standard treatments. However, what is considered a standard treatment may vary widely between clinicians, no less than between countries, and SIOPE have wisely advised that careful thought is given to the definition.” According to SIOPE president Gilles Vassal (Institut Gustave-Roussy, Villejuif, France) and SIOPE board member Pamela Kearns (University of Birmingham, Birmingham, UK), “The EC have clearly accepted the criticisms levelled against the Directive, notably the negative impact the Directive had on non-commercial trials and have introduced measures to facilitate academic trials through proportionate regulation”. Vassal and Kearns believe that the introduction of the low-intervention trial category is a huge step towards proportionate regulation, particularly with respect to most paediatric oncology trials in which the aim is to optimise the use of currently available licensed drugs. Another notable principle in the CTR is the requirement for a national indemnification mechanism. According to Vassal and Kearns, “The current requirement for a trial sponsor to provide insurance cover for clinical trials has impeded
progress in international academic collaborations due to the prohibitive insurance premiums that are disproportionate to the insured risk. Although there may be reluctance from member states to adopt national insurance schemes, due to an unfounded perception of high costs, we strongly urge the European Parliament to ensure they are mandated.” Carmen Bell (Insurance Europe, Brussels, Belgium) offers a solution in the form of a voluntary insurance system to enable insurers and their customers to negotiate more freely and enhance the insurer’s ability to design suitable cover at economically practicable costs. “This voluntary system would be most beneficial, however, if applied to all clinical trials, regardless of the level of intervention”, she said. Adam Cohen (Centre for Human Drug Research, Leiden, Netherlands), however, has reservations about the EC’s proposal for the CTR, explaining that “SIOPE’s comments are an example of the many thoughtful remarks that are made about the details of the new CTR throughout Europe. Until now the EC has shown very little flexibility in moving from the original text, so I am not hopeful this work will pay off. Much more important is that the basic and serious flaws in the CTR are not addressed. The illogical dual approach of approval with one country and many ethics committees will make the system crash. Also the system of approval by single member states without a central quality institution that guards that the differences in quality of science between member states will not lead to dangerous situations is a serious liability. We need to be concerned that the CTR does not go the way of the euro through lack of centralised control.”
Farhat Yaqub www.thelancet.com/oncology Vol 14 April 2013