Clinical Trials of New Drug Products: What Gets Compared to Whom

Charles Joseph Kowalski; Adam Joel Mrdjenovich

doi:doi:10.11648/j.ajcem.20150304.19

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Clinical Trials of New Drug Products: What Gets Compared to Whom

Charles Joseph Kowalski, Adam Joel Mrdjenovich

Published in American Journal of Clinical and Experimental Medicine (Volume 3, Issue 4)

Received: 11 June 2015 Accepted: 21 June 2015 Published: 3 July 2015

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Abstract

Two of the most controversial aspects of phase III clinical trial design are the choice of the control group(s) and the choice of the outcome variable(s). Each of these choices has overlapping scientific and ethical ramifications, and the tension between maximizing scientific validity on the one hand, and protecting the rights and welfare of the human participants in the trial on the other, is the main source of the controversy. The intensity of the debate is increased whenever these choices are motivated not by scientific or ethical principles, but are driven by conflicts of interest. And so it comes to pass that in testing the safety and efficacy of new drug products, when study design choices are made more to achieve rapid market approval than to accurately assess safety and efficacy, thereby putting the welfare of both the trial participants and future patients at risk, the public and its advocates will recoil. In this paper, we study two issues of this kind: the use of placebo controls when an established intervention for the condition under consideration exists, and the use of surrogate outcome measures. There is a rich and growing literature on both of these topics and we will have little to contribute to a greater theoretical understanding of either of them. Our aim is to point to the ethical ramifications of these choices in the context of clinical trials of new drug products, and to suggest how these choices may be better made to serve public health interests. What is to come is portended by the observation that, “In the United States, the long tradition of leaving to the pharmaceutical industry the task of evaluating the efficacy and safety of its products has permitted manufacturers to make study design choices that largely determine the shape of the answers eventually provided by the trials” (Psaty and Weiss, 2007, p. 330).

Published in	American Journal of Clinical and Experimental Medicine (Volume 3, Issue 4)
DOI	10.11648/j.ajcem.20150304.19
Page(s)	178-188
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2015. Published by Science Publishing Group

Keywords

Phase III Clinical Trials, Trial Design, Drug Safety and Efficacy

References

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Charles Joseph Kowalski, Adam Joel Mrdjenovich. (2015). Clinical Trials of New Drug Products: What Gets Compared to Whom. American Journal of Clinical and Experimental Medicine, 3(4), 178-188. https://doi.org/10.11648/j.ajcem.20150304.19

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Charles Joseph Kowalski; Adam Joel Mrdjenovich. Clinical Trials of New Drug Products: What Gets Compared to Whom. Am. J. Clin. Exp. Med. 2015, 3(4), 178-188. doi: 10.11648/j.ajcem.20150304.19

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Charles Joseph Kowalski, Adam Joel Mrdjenovich. Clinical Trials of New Drug Products: What Gets Compared to Whom. Am J Clin Exp Med. 2015;3(4):178-188. doi: 10.11648/j.ajcem.20150304.19

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@article{10.11648/j.ajcem.20150304.19,
  author = {Charles Joseph Kowalski and Adam Joel Mrdjenovich},
  title = {Clinical Trials of New Drug Products: What Gets Compared to Whom},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {3},
  number = {4},
  pages = {178-188},
  doi = {10.11648/j.ajcem.20150304.19},
  url = {https://doi.org/10.11648/j.ajcem.20150304.19},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20150304.19},
  abstract = {Two of the most controversial aspects of phase III clinical trial design are the choice of the control group(s) and the choice of the outcome variable(s). Each of these choices has overlapping scientific and ethical ramifications, and the tension between maximizing scientific validity on the one hand, and protecting the rights and welfare of the human participants in the trial on the other, is the main source of the controversy. The intensity of the debate is increased whenever these choices are motivated not by scientific or ethical principles, but are driven by conflicts of interest. And so it comes to pass that in testing the safety and efficacy of new drug products, when study design choices are made more to achieve rapid market approval than to accurately assess safety and efficacy, thereby putting the welfare of both the trial participants and future patients at risk, the public and its advocates will recoil. In this paper, we study two issues of this kind: the use of placebo controls when an established intervention for the condition under consideration exists, and the use of surrogate outcome measures. There is a rich and growing literature on both of these topics and we will have little to contribute to a greater theoretical understanding of either of them. Our aim is to point to the ethical ramifications of these choices in the context of clinical trials of new drug products, and to suggest how these choices may be better made to serve public health interests. What is to come is portended by the observation that, “In the United States, the long tradition of leaving to the pharmaceutical industry the task of evaluating the efficacy and safety of its products has permitted manufacturers to make study design choices that largely determine the shape of the answers eventually provided by the trials” (Psaty and Weiss, 2007, p. 330).},
 year = {2015}
}

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TY  - JOUR
T1  - Clinical Trials of New Drug Products: What Gets Compared to Whom
AU  - Charles Joseph Kowalski
AU  - Adam Joel Mrdjenovich
Y1  - 2015/07/03
PY  - 2015
N1  - https://doi.org/10.11648/j.ajcem.20150304.19
DO  - 10.11648/j.ajcem.20150304.19
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 178
EP  - 188
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20150304.19
AB  - Two of the most controversial aspects of phase III clinical trial design are the choice of the control group(s) and the choice of the outcome variable(s). Each of these choices has overlapping scientific and ethical ramifications, and the tension between maximizing scientific validity on the one hand, and protecting the rights and welfare of the human participants in the trial on the other, is the main source of the controversy. The intensity of the debate is increased whenever these choices are motivated not by scientific or ethical principles, but are driven by conflicts of interest. And so it comes to pass that in testing the safety and efficacy of new drug products, when study design choices are made more to achieve rapid market approval than to accurately assess safety and efficacy, thereby putting the welfare of both the trial participants and future patients at risk, the public and its advocates will recoil. In this paper, we study two issues of this kind: the use of placebo controls when an established intervention for the condition under consideration exists, and the use of surrogate outcome measures. There is a rich and growing literature on both of these topics and we will have little to contribute to a greater theoretical understanding of either of them. Our aim is to point to the ethical ramifications of these choices in the context of clinical trials of new drug products, and to suggest how these choices may be better made to serve public health interests. What is to come is portended by the observation that, “In the United States, the long tradition of leaving to the pharmaceutical industry the task of evaluating the efficacy and safety of its products has permitted manufacturers to make study design choices that largely determine the shape of the answers eventually provided by the trials” (Psaty and Weiss, 2007, p. 330).
VL  - 3
IS  - 4
ER  -

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Charles Joseph Kowalski

Health and Behavioral Sciences Institutional Review Board, Office of Research, University of Michigan, Ann Arbor, MI, USA
Adam Joel Mrdjenovich

Health and Behavioral Sciences Institutional Review Board, Office of Research, University of Michigan, Ann Arbor, MI, USA

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Charles Joseph Kowalski, Adam Joel Mrdjenovich. (2015). Clinical Trials of New Drug Products: What Gets Compared to Whom. American Journal of Clinical and Experimental Medicine, 3(4), 178-188. https://doi.org/10.11648/j.ajcem.20150304.19

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Charles Joseph Kowalski; Adam Joel Mrdjenovich. Clinical Trials of New Drug Products: What Gets Compared to Whom. Am. J. Clin. Exp. Med. 2015, 3(4), 178-188. doi: 10.11648/j.ajcem.20150304.19

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AMA Style

Charles Joseph Kowalski, Adam Joel Mrdjenovich. Clinical Trials of New Drug Products: What Gets Compared to Whom. Am J Clin Exp Med. 2015;3(4):178-188. doi: 10.11648/j.ajcem.20150304.19

Copy | Download

@article{10.11648/j.ajcem.20150304.19,
  author = {Charles Joseph Kowalski and Adam Joel Mrdjenovich},
  title = {Clinical Trials of New Drug Products: What Gets Compared to Whom},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {3},
  number = {4},
  pages = {178-188},
  doi = {10.11648/j.ajcem.20150304.19},
  url = {https://doi.org/10.11648/j.ajcem.20150304.19},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20150304.19},
  abstract = {Two of the most controversial aspects of phase III clinical trial design are the choice of the control group(s) and the choice of the outcome variable(s). Each of these choices has overlapping scientific and ethical ramifications, and the tension between maximizing scientific validity on the one hand, and protecting the rights and welfare of the human participants in the trial on the other, is the main source of the controversy. The intensity of the debate is increased whenever these choices are motivated not by scientific or ethical principles, but are driven by conflicts of interest. And so it comes to pass that in testing the safety and efficacy of new drug products, when study design choices are made more to achieve rapid market approval than to accurately assess safety and efficacy, thereby putting the welfare of both the trial participants and future patients at risk, the public and its advocates will recoil. In this paper, we study two issues of this kind: the use of placebo controls when an established intervention for the condition under consideration exists, and the use of surrogate outcome measures. There is a rich and growing literature on both of these topics and we will have little to contribute to a greater theoretical understanding of either of them. Our aim is to point to the ethical ramifications of these choices in the context of clinical trials of new drug products, and to suggest how these choices may be better made to serve public health interests. What is to come is portended by the observation that, “In the United States, the long tradition of leaving to the pharmaceutical industry the task of evaluating the efficacy and safety of its products has permitted manufacturers to make study design choices that largely determine the shape of the answers eventually provided by the trials” (Psaty and Weiss, 2007, p. 330).},
 year = {2015}
}

Copy | Download

TY  - JOUR
T1  - Clinical Trials of New Drug Products: What Gets Compared to Whom
AU  - Charles Joseph Kowalski
AU  - Adam Joel Mrdjenovich
Y1  - 2015/07/03
PY  - 2015
N1  - https://doi.org/10.11648/j.ajcem.20150304.19
DO  - 10.11648/j.ajcem.20150304.19
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 178
EP  - 188
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20150304.19
AB  - Two of the most controversial aspects of phase III clinical trial design are the choice of the control group(s) and the choice of the outcome variable(s). Each of these choices has overlapping scientific and ethical ramifications, and the tension between maximizing scientific validity on the one hand, and protecting the rights and welfare of the human participants in the trial on the other, is the main source of the controversy. The intensity of the debate is increased whenever these choices are motivated not by scientific or ethical principles, but are driven by conflicts of interest. And so it comes to pass that in testing the safety and efficacy of new drug products, when study design choices are made more to achieve rapid market approval than to accurately assess safety and efficacy, thereby putting the welfare of both the trial participants and future patients at risk, the public and its advocates will recoil. In this paper, we study two issues of this kind: the use of placebo controls when an established intervention for the condition under consideration exists, and the use of surrogate outcome measures. There is a rich and growing literature on both of these topics and we will have little to contribute to a greater theoretical understanding of either of them. Our aim is to point to the ethical ramifications of these choices in the context of clinical trials of new drug products, and to suggest how these choices may be better made to serve public health interests. What is to come is portended by the observation that, “In the United States, the long tradition of leaving to the pharmaceutical industry the task of evaluating the efficacy and safety of its products has permitted manufacturers to make study design choices that largely determine the shape of the answers eventually provided by the trials” (Psaty and Weiss, 2007, p. 330).
VL  - 3
IS  - 4
ER  -

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