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Would Centralizing Clinical Trials Reduce Overall Funding?
Dsclar 16:31, 8 March 2006 (EST)
The post below by MEF notes that industry would be unlikely to support a system of centralizing clinical trials. I agree that we could expect industry resistence. I also wonder if would could expect an overall decline in research funding. Industry currently provides significant funding for clinical trials because it stands to gain from these investments. To match this level of funding through a system of taxation, taxes would have to be unpalatably high. More likely, taxes would be notched down some and overall funding for clinical trials will decline. In terms of overall funding, there is something to be said for industry's ability to pursue its self-interest.
While I wouldn't dismiss the suggestion of centralizing clinical trials, I do agree that there a lot of challenges to overcome if we're to implement such a system.
Centralizing Clinical Trials
Per our discussion today, in the drug-approval process, the interest in characterizing the safety and efficacy of an NCE (new chemical entity) or biologic is weighed against the goal of getting a (at least for this hypothetical) life-saving product to the market as quickly as possible. The aim of course is to minimize lives lost and maximize lives saved by optimizing the balance between time to market and characterization of hazards.
Moving to a centralized organization that would manage clinical trials with minimal (or at least reduced) oversight/participation by the manufacturer, could adversely alter the above-mentioned objective. First of all, to undertake such a dramatic paradigm shift would require a huge investment of time and money. Assuming that these initial burdens are surmountable (who's going to pay the up front costs?), there will still be a learning period -- a period in which the bureaucratic kinks are worked out and the system undergoes tweaking to improve efficiency -- and it is conceivable that this will result in an increase in the time that an NCE or biologic will spend between the pre-clinical period and approval. Were this to occur, more people in need of this life-saving medicine will die than under the current system.
There are other reasons to think that the act of segregation of the manufacturer from the trials, which is ostensibly the reason for the proposal in the first place, would further slow the approval process. The manufacturer takes great care to choose the particular indication for a drug, factoring in, among other things, the desire to access a market that will allow them to recoup their investment and a disease/client population that is likely to afford favorable results wrt safety and efficacy. As clinical trials are underway, manufacturers moniter the results and can stop the trials (and minimize their financial loss) if the safety or efficacy results are less than desirable. They then are free to reevaluate their options (wrt indication) and can redesign clinical trials, for example, by focusing instead at a subpopulation that is more likely to provide the desired results. Or, if the results are outstanding early in a trial, they can enter discussions with the FDA about redesigning the future phases of clinical trials in the interest of accelerating approval. If the manufacturers were kept too segregated from the data and from the execution of the clinical trials, there is a risk that the time that a drug will take to get to market will be further slowed. [And at the very least, the cost-benefit analysis currently used in the selection of indication will be altered.]
The desire expressed in lecture today, that of minimizing the corruption or suppression of data, certainly does become compelling when lives are unnecessarily lost as a result. Yet it is hard for me to imagine that there will be industry support for such a system and equally hard to imagine that the FDA will be supportive of adding potential delays into the drug approval process. An alternative to centralizing clinical trials, that might wind up saving more lives in the long run, would be to invest in a system of in-depth post-market scrutiny. By setting up an adverse-effects database (by, e.g., taking advantage of hospitals' incident reporting systems that are already in place), we arguably could catch, in more timely fashion than at present, not only the dangers that were obscured by the few confused souls in the industry, but also the dangers that simply don't show up in the relatively small clinical trials that are affordable under our current regime. The outcome might be a much larger number of lives saved than could be removed by reducing impropriety [I don't have any numbers, sorry].
Regarding the appearrance of impropriety, the suggestion presented in class of mandating the disclosure of financial interests of those conducting studies to pthe otential trial participants should be enough to rectify the limitations of "informed consent." -- MEF
How Corporate Money Distorts Scholarship
The bulk of the discussion last week seemed directed to the worry that corporate funding of scientific research can lead to journal articles that are false, misleading and/or dishonest (tobacco-funded research is the paradigm example).
It seems to me that the real worry is simpler, less conspiratorial, but perhaps more concerning: when pharmaceuticals give large financial incentives to authors who write articles in favor of their drugs, and this is the only major source of funding for articles in the field, it will likely turn out that the only sort of articles that appear are those that confirm the benefits of pharmaceutical drugs. Articles that expose dangers in drugs and developing technologies will tend not to appear because there is no money in them. This can give the impression that drugs, and other developing technologies, are safer than they are, because only positive articles tend to appear.
The biggest problem is thus not that the pharmaceutical-funded articles are defective, but that pharmaceutical-unfriendly articles tend to be silenced by market forces (there's no money in them).
From this perspective, it seems to me that there are some pretty simple ways to make the situation better. Some ideas: journals could take some initiative and promise to dedicate a percentage of their pages to articles that have not received major outside funding; universities could take some initiative and give their own funding to professors who wish to write non-pharmaceutical-funded articles on topics relating to the industry; finally, individual researchers could take some initiative and pledge to devote some of their time to pieces that are not funded by the industry. -seth
Re: GTC's failure to receive European approval
In relation to the article that Gary sent us last week regarding the major decline in the value of GTC Biotherapeutics when the European regulators failed to approve their novel drug for use in humans: I was wondering if anyone knew how much weight other regulatory authories, ex: FDA, give to refusals by other regulatory authorities? And if a great deal of weight is granted to these refusals, how much more research would need to be done to have a realistic chance of being approved next time around?
The case of GTC Biotherapeutics is particularly interesting to me because the facility where the goats are kept is in my hometown of Charlton, MA, which I believe the article refers to as "very rural." The facility is quite amazing and my friend actually worked there for several summers. Laurieburlingame 15:20, 27 February 2006 (EST)
Scientific v. Judicial Searches for Truth
In class, Professor Krimsky warned that with tort reform, “you’re going to lose a lot of knowledge that we get through litigation,” such as the information brought to light by the tobacco litigation. In his article The Funding Effect in Science, he elaborates, explaining that “through the tobacco litigation and the discovery process, internal documents of cigarette manufacturers became public and revealed a systematic campaign to construct a science around tobacco safety, while attempting to dismiss as 'junk science' findings that connect tobacco use to excess morbidity and mortality”(55). He states further that the research funded by the tobacco industry “was designed as advocacy science” (56). It is striking that the very problem Krimsky frames – that science is losing its objective methodology for truth-seeking and replacing it with the biased, advocacy method of the judicial system – is exposed by the advocacy method of the courts.
What is it about scientific peer testing (“objective skepticism”) that differentiates it from a defense counsel’s testing of the prosecution or plaintiff’s version of the truth?
One might argue that judicial and scientific methods are not so different. As the literary and social theorists Krimsky mentions observed, scientists, even working out of their own pockets, are always biased in favor of finding positive results for their hypotheses by the possibility of reputational and financial success, as well as by normative assumptions that blind them to possible weakness in their hypotheses. These biases will lead them to become “advocates” for their projects, both in the research and presentation stages.
One might instead argue that traditional scientific and advocacy methods are in fact different because they serve different goals. Objective accuracy is favored by science because our physical world would fall apart if scientists and technicians ignored fundamental principles, like the laws of gravity. On the other hand, as Professor Nesson proposed to his Evidence class last term, the judicial system favors community acceptance and the finality of its verdicts. These goals are best served if a coherent narrative can be told about the disputed factual event, even in cases where numeric probabilities do not favor the likelihood of the ‘truth’ of that story. While the finality and acceptability of verdicts is important for social peace and the predictability of law, objective science states its results more tentatively in a way that they may be “debated in the open literature” (53).
What is it about science that feeds our impulse to test it again and again? What is it about social conflicts that leads us to bury them in the finality of verdicts? Is it only the utilitarian goals just mentioned? Are scientific truths harder and social interests more malleable? How, then, did the social system bring to light the failings of the scientific community in the case of tobacco?
Krimsky writes that the financial interest of a scientist does not become part of the public debate, which may answer the tobacco question in part. His article further suggests that unequal funding of various viewpoints in our increasingly advocacy-science oriented system produces biased results. The same can be said of the court system, where money can buy a better lawyer and therefore a better case. If it appears that the trend in science is toward advocacy science, should the government fund otherwise under-researched areas and alternative hypotheses the way it funds our advocacy-legal system by supplying defense attorneys to poor people? Or is it possible to regulate science funding to keep results more objective? -Laurie Brown
