Abstract
Background
This study uses the data from many of the mandatory fields in ClinicalTrials.gov to examine changes, possibly leading to more complexity in the design and execution of commercially sponsored phase 3 clinical trials.
Methods
In this analysis we compare baseline year 2008 data, when a broad number of the protocol/study design and execution variables became mandatory, with the data from the last full year of results, 2013.
Results
There has been relatively little change in the protocol and study design over the years covered in this study. The most pronounced change is associated with single-patient duration: there is a significant increase in the period of time a patient is treated in the study protocol. The study also highlights an important methodological issue: many of the claims in print about complexity have yet been substantiated through the use of peer-reviewed data or in settings where others can interrogate the results.
Conclusions
In general, there is limited evidence for significant increases in the study and protocol design and execution of phase 3 clinical trials sponsored by pharmaceutical companies.
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US Food and Drug Administration, Center for Drug Evaluation and Research. Novel New Drugs 2013 Summary. Published January 2014. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM381803.pdf. Accessed December 12, 2014.
Cepton Strategies. Pharmaceuticals mergers & acquisitions—Mapping 15 years of M&A deals in the pharmaceuticals industry. Published 2013. http://www.cepton.net/CEPTON_M&A_DINA4_150413.pdf. Accessed December 12, 2014.
Hammeke K. What can 2013 Outsourcing trends lead us to expect in 2014? Outsourced Pharma. Published December 2013. http://www.outsourcedpharma.com/doc/what-can-outsourcing-trends-lead-us-to-expect-in-0001. Accessed December 12, 2014.
US Congress, Congressional Budget Office. A CBO Study—Research and Development in the Pharmaceutical Industry, Figure 2.2, page 10. Published October 2006. http://www.cbo.gov/sites/default/files/cbofiles/ftpdocs/76xx/doc7615/10-02-drugr-d.pdf. Accessed December 12, 2014.
PhRMA 2013 Profile. Table 4: R&D by function, PhRMA Member Companies: 2011. Published July 2013. http://www.phrma.org/sites/default/files/pdf/PhRMA%20Profile%202013.pdf. Accessed December 12, 2014.
English R, Lebovitz Y, Griffin R. Transforming clinical research in the United States: challenges and opportunities [workshop summary]. Forum on Drug Discovery, Development and Translation. Institute of Medicine. 2010.
Califf RM, Filerman GL, Murray RK, Rosenblatt M. The clinical trials enterprise in the United States: a call for disruptive Innovation. April 2012. Institute of Medicine of the National Academies.
Singer S. Outsourcing of drug trials is faulted. The New York Times. February 2009. http://www.nytimes.com/2009/02/19/business/19clinic.html. Accessed December 12, 2014.
Rai S. Drug companies cut costs with foreign clinical trials. The New York Times. February 2005. http://www.nytimes.com/2005/02/24/business/24clinic.html?8bl. Accessed December 12, 2014.
Harris G. Report assails FDA oversight of clinical trials. The New York Times. September 2007. http://www.nytimes.com/2007/09/28/health/policy/28fda.html?adxnnl=1&adxnnlx=1403237826-CUXp5v4t0jp6sacZye/TNA. Accessed December 12, 2014.
Mansell M. Offshoring raises concerns about trial oversight, says SOMO. PharmaTimes online. February 2011. http://www.pharmatimes.com/Article/11-02-22/Offshoring_raises_concerns_about_trial_oversight_says_SOMO.aspx?rl=1&rlurl=/11-10-17/US_CRO_market_to_exceed_20_billion_by_2017.aspx. Accessed December 12, 2014.
Buzzell RD, Gale BT. The PIMS Principles: Linking Strategy to Performance. New York, NY: The Free Press; 1987.
Sacher AG, Le LW, Leighl NB. Shifting patterns in the interpretation of phase III clinical trial outcomes in advanced non-small-cell lung cancer: the bar is dropping. J Clin Oncol. 2014;32:1407–1411.
Glickman SW, McHutchinson JG, Peterson ED, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009;360:816–823.
Bill Gwinn. Finding the best clinical trial investigators. Summit for clinical operations executives. OPTUMInsight and Quality Metric. Published February 2012. https://www.qualitymetric.com/Portals/0/Uploads/Documents/Public/SCOPEGwinn_2-5-2012_ForWebsite.pdf. Accessed December 12, 2014.
Getz K, Campo R, Kaitin K. Variability in protocol design complexity by phase and therapeutic area. Drug Information Journal. 2011;45:413–20.
Getz K, Zuckerman R, Cropp A, Hindle A, Krauss R, Kaitin K. Measuring the incidence, causes, and repercussions of protocol amendments. Drug Information Journal. 2011;45:265–275.
Frank G. Current challenges in clinical trial patient recruitment and enrollment. SoCRA SOURCE. February 2004: 30.
Williams S. Clinical trials recruitment and enrollment: attitudes, barriers, and motivating factors. A summary of literature and market research reports held by NCI as of August 2004. http://cro.rbhs.rutgers.edu/documents/clinical_trials_recruitment_and_enrollment.pdf.
Bourgeois FT, Murthy S, Mandi KD. Outcome reporting among drug trials registered in ClinicalTrials.gov. Ann Intern Med. 2010;153(3):158–166.
Tse T, Williams RJ, Zarin DA. Reporting “basic results” in ClinicalTrials.gov. Chest. 2009;136:295–303.
Prayle AP, Hurley MN, Smyth AR. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study. BMJ. 2012;344. https://doi.org/10.1136/bmj.d7373. Published January 3, 2012.
Gopal RK, Yamashita TE, Prochazka AV. Research without results: inadequate public reporting of clinical trial results. Contemp Clin Trials. 2012;33(3):486–491.
Riveros C, Dechartres A, Perrodeau E, Habeef R, Boutron I, Ravaud P. Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals. PLoS Med. 2013; 10(12):e1001566.
Hartung DM, Zarin DA, Guise JM, McDonagh M, Paynter R, Helfand M. Reporting discrepancies between the ClinicalTrials. gov results database and peer-reviewed publications. Ann Intern Med. 2014;160:477–483.
Tasneem A, Aberle L, Ananth H, et al. The database for aggregate analysis of ClinicalTrials.gov (AACT) and subsequent regrouping by clinical specialty. PLoS One. 2012;7(3):e33677.
Rasmussen N, Lee K, Bero L. Association of trial registration with the results and conclusions of published trials of new oncology drugs. Trials. 2009;10:116.
Ross JS, Mulvey GK, Hines EM, Nissen SE, Krumholz HM. Trial publication after registration in ClinicalTrials.gov: a cross- sectional analysis. PLoS Med. 2009;6(9):e1000144.
Viergever RF, Ghersi D. The quality of registration of clinical trials. PLoS One. 2011;6(2):e14701.
Pasquali SK, Lam WK, Chiswell K, Kemper AR, Li JS. Status of the pediatric clinical trials enterprise: an analysis of the US ClinicalTrials.gov registry. Pediatrics. 2012;130(5): e1269–e1277.
Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007–2010. JAMA. 2012;307(17):1838–1847.
Roumiantseva D, Carini S, Sim I, Wagner TH. Sponsorship and design characteristics of trials registered in ClinicalTrials.gov. Contemp Clin Trials. 2013;34:348–355.
Glass H, Glass L, DiFrancesco J. ClinicalTrials.gov: an underutilized source of research data about the design and conduct of commercial clinical trials. Therapeutic Innovation & Regulatory Science. 2015;49;218–224.
Marchenko O, Fedorov V, Lee JJ, Nolan C, Pinheiro J. Adaptive clinical trials: overview of early-phase designs and challenges. Therapeutic Innovation & Regulatory Science. 2014;48:20–30.
Parke T, Dragalin V, Turkoz I, Marchenko O, Haynes V. Adaptive design applied to identification of the minimum effective dose in schizophrenia: simulations of scientific and commercial value. Therapeutic Innovation & Regulatory Science. 2014;48(1):41–50.
Maca J, Dragalin V, Gallo P. Adaptive clinical trials: overview of phase III designs and challenges. Therapeutic Innovation & Regulatory Science. 2014;48(1):31–40.
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Glass, H.E., DiFrancesco, J.J., Glass, L.M. et al. Are Phase 3 Clinical Trials Really Becoming More Complex?. Ther Innov Regul Sci 49, 852–860 (2015). https://doi.org/10.1177/2168479015583725
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DOI: https://doi.org/10.1177/2168479015583725