Bushey -1

Pharmaceuticals and the State

“Criminal law alone does not assure compliance as long as those corporations

that are controlled exercise political control and influence over regulatory

agencies and courts. What is needed is greater political control by the public

over the corporations and their power and influence in the political economy.

And only with basic changes in the culture and structure of American society

will there be a solution to corporate crime.” Quinney[1]

In a capitalist system, such as the ones which Canada and the United States provide, profit and organizational growth is the number one priority of corporations and governments alike. However, to both these organizations profits and survival are only guaranteed by the customers and citizens they provide their services and products to. This is a fact which seems to have been forgotten by both as they strive for economic gain. This paper will look at the pharmaceutical industries interaction with the state by focusing on the drug Vioxx and its creator Merck & Co, Inc. In their interaction, I contend, there is circumstantial evidence of state-corporate crime along with solid evidence of corporate crime in the part of Merck. This paper will begin with a history of Vioxx, followed by the Canadian process of drug approval, analysis of the relationship between the pharmaceutical industry and the Canadian government, description of the corporate crime theories involved, and finally with the recommendation of appropriate regulation.

History

A history of Vioxx cannot take place without first describing the biological actions in which Vioxx takes once inserted into the human body. Aspirin, along with other ibuprofen drugs, inhibit two enzymes in the human body, Cox-1 and Cox-2, both of which are involved in pain and inflammation. The inhibition of the Cox-1 enzyme increases the possibility of ulcers and internal bleeding due to the fact that it reduces the bloods ability to clot, at the same time however, this also helps reduce the risk of heart failure.[2]The inhibiting of Cox-2 on the other hand was seen to be responsible for the killing pain aspect. Merck, thus, set out to create a drug in which they could inhibit only the Cox-2 enzyme without inhibiting Cox-1, the result was Vioxx. This new drug offered the ability to reduce arthritic pain without the risk of the gastrointestinal side effects. The problem with this, however, is that research showed that Vioxx may actually cause an increase in blood clotting in turn leading to an increased risk of heart failure or stroke.[3]It has now been shown that Merck knew of these effects and chose not to inform Health Canada or the FDA, the American Food and Drug Administration, nor would they allow for the publishing of studies conducted by them which showed adverse cardiovascular events.[4]Vioxx, however, was approved in late 1999. In 2000 researchers began to question the safety of Vioxx and in 2002 a small warning was placed at the bottom of the bottle stating that there may be adverse cardiovascular risks. Finally, in 2004 Merck pulled Vioxx off the shelves around the world because the study APPROVedetermined that Vioxx doubled the risks of heart attack and stroke amongst long term (18 months) users.[5]There have been thousands of lawsuits brought against Merck by individuals whom were hurt by Vioxx or by the families of people who weren’t lucky enough to be just hurt by it. A woman in Texas has recently been rewarded $253 million dollars for the death of her husband in which Merck was found liable for his death. This brings into question how it was possible for this drug to get past Health Canada and into Pharmacies across Canada.

Canada Health and Drug Approval

In Canada, a scientist must first develop and purify a chemical or biological substance and test it on biological tissue samples or small animals. If it is determined that there are significant biochemical, physiological, or behavioral changes to the specimen then the researchers must then determine the proper dosages by further animal testing; only then may they apply to the Therapeutic Products Directorate (TPD) for human clinical trials. The TPD is the main body in Canada for regulating, evaluating, and monitoring of pharmaceuticals.[6]

Once this has been approved they can then begin testing on healthy humans “to evaluate the half-life, absorption, distribution, metabolism and excretion of a drug in the human species.”[7]The substance is then ready to be tested on the potential consumers of this drug, the ill. These trials are used to determine dose and dose frequency. The next phase is conducted on a large number of patients whom are either given a placebo or the actual substance in development. This is a random, double blind study so that neither the subject nor the tester know which drug has been given. If it is proven based on these studies that “the drug has potential therapeutic value that outweighs the risks associated with its use”[8] then the TPD will review all of the clinical data and make its decision.

There were multiple problems in the review process for both the TPD and for Merck in the clinical stages of Vioxx. In both Canada and the US Vioxx was “fast-tracked” to be put on the market quicker.[9] The TPD “allows for a faster review to make available promising drug products for life-threatening or severely debilitating conditions, such as cancer, AIDS, or Parkinson's Disease, for which there are few effective therapies already on the market.”[10] The drug Vioxx does not seem to fit into the alleged guidelines for fast review as it is very much a “me too” drug, a drug which essentially is just doing the same as other drugs already on the market. The drug Celecoxib had already been approved for the market so it would have been more helpful to run Vioxx through the full review process to possibly determine any adverse effects which may not have yet been captured. It has also been shown that Health Canada knew about the possible increase in adverse cardiovascular events[11] yet they still pushed the drug ahead. At the same time it can be seen that Merck was withholding pertinent information regarding the adverse effects caused by Vioxx. As early as 1996 Merck had recorded data which showed an increased risk in adverse cardiovascular events, as seen above, and emails between executives have proven that they not only knew about the effects but were working to suppress them.[12]This goes hurdles beyond the line of negligence by both Health Canada and Merck. Thousands of people in North America were seriously or fatally injured due to the adverse effects of Vioxx, effects which the patients were not even aware of. There should have been criminal sanctions or at least some form of governmental response, yet there was none. In fact, the drug was not even banned in Canada, this is a point which brings about many questions, many which due to Canada’s lack of transparency in drug regulation are left unanswerable which may lead to the impression of state-corporate crime in conjunction with Merck and the pharmaceutical industry. Michael McBane in his book about the problems of Health Canada states that this lack of transparency means proper accountability is impossible, vulnerability to industrial capture and collusion between regulator and the regulated, and industry’s scientific experts have extensive conflicts of interest while providing their expert advice.[13] Although Health Canada has been saying changes are coming for years nothing substantial has changed.

Canada and Big Pharma

The pharmaceutical industry and the Canadian government have had a close relationship for years; tied with the lack of transparency and the questionable release of various drugs, including Vioxx, there are questions of legality and morality which must be answered. “While the government may appear not to be interested in profit, it largely operates to facilitate profit-making and growth among the private sector.”[14]For example, the TPD website claims that they are attempting to speed up the process of drug approval which will benefit the consumers. Speeding up the approval process will not only put the consumers in more harm but it is a direct result of the industry contributing about half of the TBDs budget.[15]"What this (Vioxx) really demonstrates is the dangers of jumping into new drug use before all the data is really in," says Dr. Joel Lexchin, an emergency physician and professor in York's School of Health Policy and Management.[16]However, by speeding up the review process it puts the industry in the position to profit longer from the drug before the patent runs out. This conflict of interest brings into question what else the industry is getting in exchange for operating in Canada and for their monetary backing. Although they may create agencies and regulations to prevent crime by large corporations such as Merck they are often put in place for government accountability and to look like something is being done.[17] This seems, essentially, what the TPD has been charged to do.

Another question which must be answered is how can a company in charge of protecting society and saving lives market a drug so vigorously which they knew was causing severe adverse effects and in many cases causing death? As much as Merck denies it there is strict evidence to prove the contrary. In regards to the government, the lack of transparency leaves advertising and sales representatives in control of providing information about their product to doctors and consumers, often giving a biased description of their products. This includes the case of Vioxx as the C.M.A Journal noted “There is evidence that the manufacturer (Merck) tried to play down the risk in its promotional material for doctors.”[18] Sales Representatives were also ordered to practice dodging questions away from Vioxx and the adverse cardiovascular effects, which they called “Vioxx Dodge Ball”, according to leaked documents.[19]A member of the United States House of Representatives, after analysing various documents, states that “Merck sent more than 3,000 highly trained representatives into doctor's offices and hospitals armed with misleading information about Vioxx's risks.”[20] These doctors have no use but to believe what the sales representatives are saying as they, just like the majority of the Canadian population, do not have the resources to run tests to find out if what they are saying is true. If doctors could get more information regarding the drugs which they are being given to provide to their customers maybe they could form an unbiased opinion on the drugs. The information may be there but due to the privacy restrictions they are unable to access it.

As stated above, I contend, that the relationship which has formed between the drug industry and Health Canada can be seen as state-corporate crime. Health Canada ignored warning signs that Vioxx had severe adverse effects, and they did not properly regulate Merck in the ways in which they are outlined to do so. Had they followed protocol then it is unlikely that Vioxx would have ever been allowed to be released in Canada. In an article by Ronald C. Kramer et al, it is shown that these actions clearly fall under the state-corporate crime theory. Health Canada “failed to protect peoplevulnerable to potentially harmful organizational practices.”[21]

Corporate Crime Theories

The theoretical system which describes best the relationships which have been described is that of theliberal pluralist theory. It claims that behaviour is determined not by values but rather by interests. The role of the state is thus to balance interests and to come to compromises with and between groups in regards to laws. Since behaviours are not based on values, if an organization believes that it can break the law for the better interest of the company without being caught or sanctioned then they will do so. Since legislation is often formed to balance conflict, many times it is just a “smoke screen” for the public to make it look like the government is regulating certain groups, organizations most of the time feel they can get away with many illegal acts. Organizations will also try to exert pressure on the government to try and get regulatory measures that fit their organizational interests.

This is a mirror image of the current situation above. Drug company has drug which is bad for people, however, it is in their best interest to sell it because then the company will flourish. They give the government money to speed up the process of drug approval. The government creates an agency to monitor the drugs and regulate the industry so the public will think the government is doing its job and that they are safe. When it is found out that the industry broke the law, nothing is done about it because then the government will not get its money (interest).

Reccomendations

It has now been made clear that both Health Canada and Merck are at fault regarding the Vioxx debacle, but now what? Questions have been asked and must be answered. How does one prevent this from happening again? Not only in the pharmaceutical industry but in all industries. The government is charged with regulating corporate behavior and actions and clearly there is not enough regulation, not enough monitoring, and not enough transparency in the Canadian system. In regards to the corporations, they must follow strict codes of conduct, strict ethical codes, and strict governmental regulations when carrying out business. Although consumers understand that a company is trying to maximize profits in everything they also understand that if they are paying a company for a service or product then that product should not harm them and if it will harm them they should know. They should know that stringent testing had gone on and that they will not suffer unknown adverse effects from that product or service. The final thing to look at is the bonds between corporate industry and the government. Industry should not be providing funding to the government, nor should the government be allowing the industry to fully regulate itself.

The largest issue, I contend, is that of regulation. This situation occurred for the most part due to lax regulation from the government. If the government was not doing favors for the industry then it was extremely neglectful in its dealing with Vioxx but evidence, or lack of evidence in this case, would prove to agree with the former. The problem is Health Canada “continues to see the pharmaceutical industry as its customer—a vital source of funding for its activities—and not as a sector of society in need of strong regulation.”[22]They must stop protecting the industry when truly it is their citizens who should be protected.

I contend that to fix the failed state of the Canadian drug industry and put trust back into the citizens and doctors number things must happen:

1) The government must create a system in which funding cannot come directly from the drug industry. The conflict of interest is too high when the industry being regulated is directly providing funding for the regulators. As can be seen, the TPD does not have adequate funding and thus cannot perform its duties effectively. In such case, it is proposed that the industry be taxed a large sum to be given authority to license new drugs in Canada. This tax can then be pooled to be distributed as needed to the TPD.

2) The industry must not be able to perform clinical trials without supervision of a government official or all clinical trials must be facilitated by a third party or governmental organization. These facilitators would have strict pricing guidelines and would not be bale to deviate from such as to prevent the industry from “over paying”.

3) The government must remove many of its corporate privacy regulations and allow for much more transparency as well as be audited by an annual board. This would give credibility and trust back to the government from the citizens and doctors who use and prescribe the products. Additionally, this would allow for academics and researchers to study the reasons for disallowing or allowing a drug which could lead to further studying of the drug and regulations.

4) The government must monitor drugs after they have been approved and put on the market enhancing the possibility of detecting further adverse effects which may not have been found during the clinical trials.

These proposed regulatory changes, although drastic and costly, are steps in the right direction to instill trust and accountability back into the government and the pharmaceutical industry. If every step of the process is monitored and controlled by non biased agents then the issues which arose in the past should no longer be relevant. However, as stated these outlined proposals would be costly and if a government did not have the resources to implement the proposed monitoring guidelines they may be better off creating enforced self-regulation legislation. Under this system, the government would have each company write “a set of rules tailored to the unique set of contingencies facing that firm.”[23] These would then be approved or denied by a regulatory agency and also put against a committee of interested parties and citizens. The cost saving aspect of this form of governance is the fact that each corporation would have to create an independent inspectorial body to inspect and enforce the rules. The government would then only need to monitor that the inspectoral body is independent and that they are properly and efficiently enforcing the rules. If a company is found to be in violation the government would also punish them by law. There are many benefits to this beyond cost as well considering, for example, that many governmental inspectors are not trained in the field which they inspect they would have harder times inspecting the material and digging to find problems. Both proposed guidelines would be much better then the system already in place and would certainly help prevent catastrophes like the Vioxx one.