Health  Vol.3 No.12 , December 2011
Sponsor-investigator-relationship: challenges, recent regulatory developments and future legislative trends
ABSTRACT
Correct definition and management of sponsor- investigator relationship is of central importance for planing and executing clinical trials. During the last decade, there have been numerous modifications of guidelindes, international and national legislations and regulations. This implicated various alterations and shifts of essential responsibilities and tasks relating to the investigator, sponsor or sponsor-investigator what raised financial, clinical and ethical issues. First experiences with these new regulations and legislations are discussed together with international differences and their impacts on clinical trials. Regarding non-commercial trials and institutional sponsorship, there are still open organizational and legal questions after national implementation of the Europeam Clinical Trials Directive in 2004, although various approaches have been suggested in recent years in Europe. Current trends and controversies are discussed as well. A literature review was performed summarizing recent experiences with current legislations and risen controversies of these new legislations showing impact on future trends.

Cite this paper
nullCiuman, R. (2011) Sponsor-investigator-relationship: challenges, recent regulatory developments and future legislative trends. Health, 3, 772-781. doi: 10.4236/health.2011.312128.
References
[1]   European Parliament and Council Directive 2001/20/EC of 4 April 2001. OJ No L121/34 of 1 May 2001.

[2]   German Drug Law (2004) 12 Gesetz zur Anderung des Arzneimittelgesetzes. Bundesgesetzblatt Teil I Nummer 41.

[3]   Wingen, F.I. and Beinhauer, K.G. (2002) Development of clinical drug trial and the formal, legal and financial scope. Internist (German), 43, 463-468.

[4]   Thompson, D.F. (1993) Understanding financial conflicts of interest. The New England Journal of Medicine, 329, 573-576. doi:10.1056/NEJM199308193290812

[5]   Weber, L.J. (2006) Profits before people? Ethical standards and the marketing of prescription drugs. Indiana University Press, Bloomington.

[6]   Montori, V.M., Smieja, M. and Guyatt, G.H. (2000) Publication bias: A brief review for clinicians. Mayo Clinic Proceedings, 75, 1284-1288. doi:10.4065/75.12.1284

[7]   Hirsch, L. (2004) Randomized clinical trials: What gets published, and when? Canadian Medical Association Journal, 170, 481-483.

[8]   Department of Health and Human Services (2004) Financial relationships and interests in research involving human subjects: Guidance for human subject protection. Federal Register Notices, 69, 26393.

[9]   De Angelis, C., Drazen, J.M., Frizelle, F.A., Haug, C., Hoey, J., Horton, R., Kotzin, S., Laine, C., Marusic, A., Overbeke, A.J., Schroeder, T.V., Sox, H.C. and Van Der Weyden, M.B. (2004) Clinical trial registration: A statement from the International Committee of Medical Journal editors. The New England Journal of Medicine, 351, 1250-1251.

[10]   Davidoff, F., DeAngelis, C.D., Drazen, J.M., Nicholis, M.G., Hoey, J., Hojgaard, L., Horton, R., Kotzin, S., Nylenna, M., Overbeke, A., Sox, H.C., Weyden, M. and Wilkes, M.S. (2001) Sponsorship, authorship and accountability. Canadian Medical Association Journal, 165, 786-788.

[11]   FDA (2006) Guidance for clinical trial sponsors on the establishment and operation of clinical trial data monitoring committees, 71FR 15421. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf

[12]   Ahmer, S., Haider, I.J., Anderson, D. and Arya, P. (2006) Do pharmaceutical companies selectively report clinical trial data. Pakistan Journal of Medical Sciences, 22, 338-346.

[13]   House of Commons Health Committee (2005) The influence of the pharmaceutical industry. Fourth Report of Session, The Stationary Office Limited, London.

[14]   Ferner, R. (2005) The influence of big pharma. BMJ, 330, 855-856. doi:10.1136/bmj.330.7496.855

[15]   Turner, E.H., Matthews, A.M., Linardatos, E., Tell, R.A. and Rosenthal, R. (2008) Selective publication of antidepressant trials and its influence on apparent efficacy. The New England Journal of Medicine, 358, 252-260. doi:10.1056/NEJMsa065779

[16]   Melander, H., Ahlqvist-Rastad, J., Meijer, G. and Beermann, B. (2003) Evidence based medicine-selective reporting from studies sponsored by pharmaceutical industry: Review of studies in new drug applications. BMJ, 326, 1171-1173. doi:10.1136/bmj.326.7400.1171

[17]   Lee, K., Bachetti, P. and Sim, I. (2008) Publication of clinical trials supporting successful new drug applications: a literature analysis. PLoS Medicine, 5, e191. doi:10.1371/journal.pmed.0050191

[18]   Rising, K., Bachetti, P. and Bero, L. (2008) Reporting bias in drug trials submitted to the Food and Drug Administration: Review of publication and presentation. PLoS Medicine, 5, e217. doi:10.1371/journal.pmed.0050217

[19]   Schott, G., Pachl, H., Limbach, U., Gundert-Remy, U., Ludwig, W.D. and Lieb, K. (2010) The financing of drug trials by pharmaceutical companies and its consequences. Part 1: A qualitative, systematic review of the literature on possible influences on the findings, protocols, and quality of drug trials. Deutsches Aerzteblatt International (German), 107, 279-285.

[20]   Schott, G., Pachl, H., Limbach, U., Gundert-Remy, U., Ludwig, W.D. and Lieb, K. (2010) The financing of drug trials by pharmaceutical companies and its consequences. Part 2: A qualitative, systematic review of the literature on possible influences on authorship, access to trial data, and trial registration and publication. Deutsches Aerzteblatt International (German), 107, 295-301.

[21]   Kaiser, J. (2008) Making clinical data widely available. Science, 322, 217-218. doi:10.1126/science.322.5899.217

[22]   PloS Medicine Editors (2008) Next stop, don’t block the doors: Opening up access to clinical trials results. PloS Medicine, 5, e160. doi:10.1371/journal.pmed.0050160

[23]   US Department of Health and Human Services (2007) Food and Drug Administration Amendments Act of 2007, P.L. 110-185. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2007/FullTextofFDAAA Law/default.htm

[24]   Hirsch, L. (2008) Trial registration and results disclosure: Impact of US legislation on sponsors, investigators, and medical journal editors. Current Medical Research and Opinion, 24, 1683-1689. doi:10.1185/03007990802114849

[25]   Mayor, S. (2005) Drug companies agree to make clinical trial results public. BMJ, 330, 109. doi:10.1136/bmj.330.7483.109

[26]   PhRMA (2009) Revised clinical trial principles reinforce PhRMA’s commitment to transparency and strengthen authorship standards (press release), Washington DC. http://www.phrma.org/sites/default/files/800/042009_clinical_trial_principles_final.pdf

[27]   Taylor, P. (2009) Emerging clinical trial locations— China. Market dynamics and regulatory environment. Business Insights Ltd, London.

[28]   Abdullahi vs. Pfizer Inc., 562 F.3d 163, 169 (2nd Cir. 2009).

[29]   European Commission (2005) Notice to Applicants. Questions & answers: Clinical trial documents, F2/BL D 2005, Brussels. http://www.ct-toolkit.ac.uk/_db/_documents/ClinicalTrialQ&A_24-01-05.pdf

[30]   Department of Health, UK. (2004) EU Clinical Trials Directive: Sponsorship responsibilities in publicly funded trials. Medicines for human use (Clinical Trials) regulations 2004. http://www.ct-toolkit.ac.uk/_db/_documents/sponsorship.pdf

[31]   Gainotti, S. and Petrini, C. (2010). Insurance policies for clinical trials in the United States and in some European countries. Journal of Clinical Research & Bioethics, 1, 1-8. doi:10.4172/2155-9627.1000001

[32]   Robinson, K. and Andrews, P.J. (2010) More trials and tribulations: The effect of the EU directive on clinical trials in intensive care and emergency medicine, five years after its implementation. Journal of Medical Ethics, 36, 322-325. doi:10.1136/jme.2009.035261

[33]   Meunier, F. and Lacombe, D. (2003) European Organisation for Research and Treatment of Cancer’s point of view. Lancet, 23, 663. doi:10.1016/S0140-6736(03)14163-3

[34]   Ono, S. and Kodama, Y. (2000) Clinical trials and the new good clinical practice guideline in Japan. An economic perspective. Pharmacoeconomics, 18, 125-141. doi:10.2165/00019053-200018020-00003

[35]   ICREL (2011) Report of project “Impact on Clinical Research of European Legislation”. http://www.efgcp.be/icrel

[36]   Therasse, P., Eisenhauer, E.A., Buyse, M. (2006) Update in methodology and conduct of cancer clinical trials. European Journal of Cancer, 42, 1322-1330. doi:10.1016/J.ejca.2006.02.006

[37]   Hemminki, A. and Kellokumpu-Lehtinen, P.L. (2006) Harmful impact of EU clinical trials directive. BMJ, 332, 501-502. doi:10.1136/bmj.332.7540.501

[38]   Morice, A.H. (2003) The death of academic clinical trials. Lancet, 361, 1568. doi:10.1016/S0140-6736(03)13211-4

[39]   Berendt, L., Hakansson, C., Bach, K.F., Dalhoff, K., Andreasen, P.B., Petersen, L.G,. Andersen, E. and Poulsen, H.E. (2008) Effect of European clinical trials directive on academic drug trials in Denmark: Retrospective study of applications to the Danish Medicines Agency, 1993-2006. BMJ, 336, 33-35. doi:10.1136/bmj.39401.470648.BE

[40]   Singer, E. (2007) Future of investigator initiated trials in EU academia. Basic & Clinical Pharmacology & Toxicology, 101, 11.

[41]   Gulland, A. (2009) Number of global clinical trials done in UK fell by two thirds after EU directive. BMJ, 338, 1052. doi:10.1136/bmj.b1052

[42]   The Commission of the European Communities (2005) Commission Directive 2005/28/EC of 8 April 2005. OJL, 91, 13-19.

[43]   European Forum for Good Clinical Practice (EFGCP) (2010) A road map initiative for clinical research in Europe. http://www.efgcp.be

[44]   Federation of the European Academics of Medicine (FEAM) (2011) Opportunities and challenges for reforming the EU clinical trials directive: An academic perspective: Statement. http://www.leopoldina.org/fileadmin/user-upload/politik/Empfehlugen/FEAM/FEAM_Statement_EU-clinical-trials-directive_2010.pdf

[45]   European Forum for Good Clinical Practice (EFGCP) (2011) Conference report: Examining the value and the impact of the EU clinical trials directive-one year into the new European GCP reality. http://www.efgcp.be/Downloads/EFGCP%20News%20Winter%202005.pdf

[46]   Demotes-Mainard, J. and Ohmann, C. (2005) European clinical research infrastructures network: Promoting harmonization and quality in European clinical research. Lancet, 365, 107-108. doi:10.1016/S0140-6736(05)17720-4

[47]   Demotes-Mainard, J., Chene, G., Libersa, C. and Pignon, J.P. (2005) Clinical research infrastructures and networks in France: Report on the French ECRIN workshop. Therapie, 60, 183-199. doi:10.2515/therapie:2005023

[48]   Bergmann, L., Berns, B., Dalgleish, A.G., von Euler, M. and Hecht, T.T. (2010) Investigator-initiated trials of targeted oncology agents: Why independent research is at risk? Annals of Oncology, 21, 1573-1578. doi:10.1093/annonc/mdq018

[49]   Clumeck, N. and Katlama, C. (2004) Call for network of centers of excellence in clinical research in Europe. Lancet, 363, 901-902. doi:10.1016/S0140-6736(04)15757-7

[50]   European Commission (2006) Guidance document on specific modalities for non-commercial clinical trials referred to in commission directive 2005/28/EC laying down the principles and detailed guidelines for good clinical practice. http://ec.europa.eu/health/files/pharmacos/docs/doc2006/07_2006/guide_noncommercial_2006_07_27_en.pdf

[51]   Moniteur Belge, Belgium. Loi relative aux Experimentations sur la Personne Humaine; 7 May 2004. http://www.ejustice.just.fgov.be/cgi_loi/change_lg.pl?language=fr&la=F&cn=2004050732&table_name=loi

[52]   Italian Medicines Agency (AIFA) (2010) Research and development working group. Feasibility and challenges of independent research on drugs: The Italian medicines agency experience. European Journal of Clinical Investigation, 40, 69-86. doi:10.1111/j.1365-2362.2009.02226.x

 
 
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