Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-22T04:42:27.277Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical Trials Registries: A Reform that is Past Due

Published online by Cambridge University Press:  01 January 2021

Jennifer L. Gold  and
David M. Studdert
Get access Rights & Permissions [Opens in a new window]

Extract

Several high-profile episodes have recently thrust drug safety and the pharmaceutical industry's practices into the spotlight. Merck's recall of the drug Vioxx, for instance, was a major news event. GlaxoSmithKline's suppression of data linking suicidal behavior among children to Paxil also galvanized tremendous public attention. What differentiates these events from the usual evolving process of scientific knowledge, and marks them with an aura of “scandal,” are questions about the propriety of corporate behavior. Who knew what, and when did they know it? Concerns are growing about the potential for industry sponsors to suppress negative results from clinical trials research. Scientists, medical journal editors, legislators, and the public have called for greater transparency in the conduct of clinical trials and the drug approval process.

Type
Article
Information
Journal of Law, Medicine & Ethics , Volume 33 , Issue 4 , Winter 2005 , pp. 811 - 820
Copyright
Copyright © American Society of Law, Medicine and Ethics 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

De Angelis, C., Drazen, J. M., Frizelle, F. A. et al, “Clinical Trial Registration: A Statement from the International Committee of Medical Journal Editors,” N. Engl. J. Med. 254 (2004): 1250–1.CrossRefGoogle Scholar
Ibid.Google Scholar
Ibid.Google Scholar
In a RCT, subjects are randomly allocated to either the treatment group, or the control group; the control group receives a placebo in lieu of the actual intervention. RCTs may be open (i.e., both the researcher and patient know which group the patient is in), single-blind (the researcher knows but the patient does not), or double-blind (neither party is aware).Google Scholar
Lillenfeld, A. M., “Ceteris Parabus: The Evolution of the Clinical Trial,” Bulletin of the History of Medicine 56 (1982): 1–18.Google Scholar
Dickersin, K. and Rennie, D., “Registering Clinical Trials,” JAMA 290 (2003): 516–523.CrossRefGoogle Scholar
Grady, D., Herrington, D., V. Bittner, et al., for the HERS Research Group, “Cardiovascular Disease Outcomes during 6.8 years of Hormone Therapy,” JAMA 288 (2002): 49–57; Hulley, S., Furberg, C., Barrett-Connor, E. et al “Non-cardiovascular Disease Outcomes during 6.8 years of Hormone Therapy: Health and Estrogen/progestin Replacement Study Follow-up (HERS II),” JAMA 288 (2002): 58–66; Writing Group for the Women's Health Initiative Investigators, “Risks and Benefits of Estrogen plus Progestin in Healthy Postmenopausal Women: Principal Results from the Women's Health Initiative Randomized Controlled Trial,” JAMA 288 (2002): 321–333.CrossRefGoogle Scholar
Shojania, K. G., Duncan, B. W., McDonald, K. M., Wachter, R. M., “Safe but Sound: Patient Safety meets Evidence-based Medicine,” JAMA 288 (2002): 508–13.CrossRefGoogle Scholar
Scherer, R. W., Langenberg, P., full publication of results initially presented in abstracts [Cochrane Methodology Review] (Oxford, England: Cochrane Library, Update Software, 2003): Issue 1. See also Dickersin, , Rennie, , supra note 6.Google Scholar
Hartling, L., Craig, W. R., Russell, K., Stevens, K., Klassen, T. P., “Factors Influencing the Publication of Randomized Controlled Trials in Child Health Research,” Archives of Pediatric and Adolescent Medicine 158 (2004): 983–7.CrossRefGoogle Scholar
Chalmers, I., “Underreporting Research is Scientific Misconduct,” JAMA 263 (1990): 1405–1408.CrossRefGoogle Scholar
See Dickersin, and Rennie, , supra note 6.Google Scholar
Callaham, M. L., Wears, R. L., Weber, E. J., Barton, C., Young, G., “Positive-outcome Bias and other Limitations in the Outcome of Research Abstracts Submitted to a Scientific Meeting,” JAMA 280 (1998): 254–257; Eloubeidi, M. A., Wade, S. B., Provenzale, D., “Factors Associated with Acceptance and Full Publication of GI Endoscopic Research Originally Published in Abstract Form,” Gastrointestinal Endoscopy 53 (2001): 275–282.Google Scholar
Stern, J. M., Simes, R. J., “Publication Bias: Evidence of Delayed Publication in a Cohort Study of Clinical Research Projects,” British Medical Journal 315 (1997): 640–645.CrossRefGoogle Scholar
Dickersin, K., Chan, S., Chalmers, T. C., Sacks, H. S., Smith, H. J. R., “Publication Bias and Clinical Trials,” Controlled Clinical Trials 8 (1987): 343–353.CrossRefGoogle Scholar
Systematic reviews and meta-analyses compile the results of all clinical trials on a particular drug or other intervention, and reevaluate its effectiveness using a greater amount of data.Google Scholar
Spitzer v. GlaxoSmithKline PLC, N.Y. Sup. Ct., No. 04/401707.Google Scholar
Ibid.Google Scholar
Ibid.Google Scholar
Ibid.Google Scholar
Martinez, B., “Glaxo Settles New York Suit over Unpublished Clinical Data,” The Wall Street Journal, August 27, 2004, at B3.Google Scholar
Huth, E. J., “Irresponsible Authorship and Wasteful Publication,” Annals of Internal Medicine 104 (1986): 257–59.CrossRefGoogle Scholar
Huston, P., Moher, D., “Redundancy, Disaggregation, and the Integrity of Medical Research,” Lancet 347 (1996): 1024–26.CrossRefGoogle Scholar
See Huston, , Moher, , supra note 23.Google Scholar
Ibid.Google Scholar
McCray, A., “Better Access to Information About Clinical Trials,” Annals of Internal Medicine 133 (2000): 609–614.CrossRefGoogle Scholar
Section 113, Information Program on Clinical Trials for Serious or Life-Threatening Diseases, Food and Drug Administration Modernization Act of 1997, Public Law 105–115.Google Scholar
National Library of Medicine, “Fact Sheet: ClinicalTrials.gov,” at <http://www.nlm.nih.gov/pubs/factsheets/clintrial.html> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
Ibid.Google Scholar
Ibid.Google Scholar
“About the metaRegister of Controlled Trials and rationale,” at <http://www.controlled-trials.com/mrct/mrct_about.asp> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
“ISRCTN FAQ”, at <http://www.controlled-trials.com/isrctn/isrctn_faqs.asp> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
PhRMA, “Update principles for conduct of clinical trials and communication of clinical trial results. June 30, 2004,” at <www.phrma.org/mediaroom/press/releases/30.06.2004.427.cfm> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
<www.lillytrials.com> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
Phase I studies are designed to establish the effects of a new drug in humans. These studies are usually conducted on small populations of healthy humans to specifically determine a drug's toxicity, absorption, distribution and metabolism. After the successful completion of phase I trials, a drug is then tested for safety and efficacy in a slightly larger population of individuals who are afflicted with the disease or condition for which the drug was developed. This is known as a Phase II study. The third and last pre-approval round of testing of a drug is conducted on large populations of afflicted patients. Phase III studies usually test the new drug in comparison with the standard therapy currently being used for the disease in question. The results of these trials usually provide the information that is included in the package insert and labeling. After a drug has been approved by the FDA, Phase IV studies are conducted to compare the drug to a competitor, explore additional patient populations, or to further study any adverse events. (From <http://www.centerwatch.com/patient/glossary.html> [last visited August 23, 2005]). [last visited August 23, 2005]).' href=https://scholar.google.com/scholar?q=Phase+I+studies+are+designed+to+establish+the+effects+of+a+new+drug+in+humans.+These+studies+are+usually+conducted+on+small+populations+of+healthy+humans+to+specifically+determine+a+drug's+toxicity,+absorption,+distribution+and+metabolism.+After+the+successful+completion+of+phase+I+trials,+a+drug+is+then+tested+for+safety+and+efficacy+in+a+slightly+larger+population+of+individuals+who+are+afflicted+with+the+disease+or+condition+for+which+the+drug+was+developed.+This+is+known+as+a+Phase+II+study.+The+third+and+last+pre-approval+round+of+testing+of+a+drug+is+conducted+on+large+populations+of+afflicted+patients.+Phase+III+studies+usually+test+the+new+drug+in+comparison+with+the+standard+therapy+currently+being+used+for+the+disease+in+question.+The+results+of+these+trials+usually+provide+the+information+that+is+included+in+the+package+insert+and+labeling.+After+a+drug+has+been+approved+by+the+FDA,+Phase+IV+studies+are+conducted+to+compare+the+drug+to+a+competitor,+explore+additional+patient+populations,+or+to+further+study+any+adverse+events.+(From++[last+visited+August+23,+2005]).>Google Scholar
Lilly, Eli, “Initiated Trials” at <http://www.liHytrials.com/initiated/initiated.html> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
Meier, B., “Drug Industry Plans Release of More Data About Studies,” New York Times, January 7, 2005.Google Scholar
At <http://clinicaltrials.gov/ct/screen/BrowseAny?path=%2Fbrowse%2Fby-sponsor%2FINDUSTRY&recruiting=false> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
See Dickersin, , Rennie, , supra note 6.Google Scholar
Couzin, J., “Legislators Propose a Registry to Track Clinical Trials from Start to Finish,” Science 305 (2004): 1695.CrossRefGoogle Scholar
Meier, B., “A Top Republican to Offer Drug Data Bill,” New York Times, December 10, 2004.Google Scholar
World Health Organization, “WHO leads drive for international coordination of clinical research,” April 2 2004. At <www.who.int/mediacentre/news/releases/2004/pr23/en/> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
Abbasi, K., “Compulsory Registration of Clinical Trials,” British Medical Journal 329 (2004): 637–638.CrossRefGoogle Scholar
“ISRCTN application form,” at <http://controlled-trials.com/isrctn/submission/> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
Cohen, P., “Medical Journals to Require Clinical Trial Registration,” New Scientist, September 9, 2004 available at <www.newsrientist.com/news/printjsp?id=ns99996378> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
Cochrane Collaboration, “What is the Cochrane Collaboration?” Available at <http://www.cochrane.org/docs/descrip.htm> (last visited August 23, 2005).+(last+visited+August+23,+2005).>Google Scholar
See for example: “EUROPA, Combating AIDS, Malaria and Tuberculosis: Commissioner Busquin in Dakar for Clinical Trials Partnership Launch,” at <http://europa.eu.int/comm/research/press/2004/pr2302en.cfm> (last visited August 23, 2005); PR Newswire, “Aeras Receives CDC Funding to Develop TB Vaccine Trial Sites in India,” at <http://sev.prnewswire.com/health-care-hospitals/20040917/DCF01917092004–1.html> (last visited August 23, 2005); NIH News Release, “New Awards, Expanded Focus for Pediatric AIDS Clinical Trials Group,” at <http://www.nih.gov/news/pr/mar2002/niaid07.htm> (last visited August 23, 2005).+(last+visited+August+23,+2005);+PR+Newswire,+“Aeras+Receives+CDC+Funding+to+Develop+TB+Vaccine+Trial+Sites+in+India,”+at++(last+visited+August+23,+2005);+NIH+News+Release,+“New+Awards,+Expanded+Focus+for+Pediatric+AIDS+Clinical+Trials+Group,”+at++(last+visited+August+23,+2005).>Google Scholar
See Abbasi, , supra note 43 and Cohen, , supra note 45.Google Scholar
Thompson, D. F., “Understanding Financial Conflicts of Interest,” N. Engl. J. Med. 329 (1993): 573–6.CrossRefGoogle Scholar
Rennie, D., “Trial Registration: A Great Idea Switches from Ignored to Irresistible,” JAMA 292 (2004): 1359–1362.CrossRefGoogle Scholar
See Rennie, , supra note 50.Google Scholar