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The Knowledge Breakdown in Medicine

Mathew Busby

Debunking Pseudoscience – Fall 2008

15-page Midterm Paper

Introduction

Medical research produces tons of information every year. One would expect those in the

medical profession to hold themselves to a high standard, but the research is subject to the same

errors and omissions that you encounter in any other research – “researchers who use the wrong

techniques (either willfully or in ignorance), use the right techniques wrongly, misinterpret their

results, report their results selectively, cite the literature selectively, and draw unjustified

conclusions.” (Altman) The research is motivated by several factors, but is still controlled by

money. Money comes from the government and private sources, medical companies which stand

to benefit from the publishing of particular research. This very quickly leads to the unethical

treatment of data and hiding of important negative results. Through direct-to-patient marketing

(which the research also partially functions as), fresh new drugs designed to treat the same old

diseases are pumped to prescribers and patients, causing cases to skyrocket in a “build it and they

will come” fashion. The problem isn’t just “a pill for every ill.” It would be virtuous to cure the

actual diseases of the world, but broadening disease definitions can cause a virtual case for every

pill a manufacturer could ever conceive – an ill for every pill. (Moynihan)

This problem can be rooted to three things: those who produce the knowledge, those who

regulate the knowledge, and those who utilize the knowledge. The drug companies who fund

countless research studies require positive results to support the time and money consumed by

the research and development of drugs to be studied. If a researcher with one of several large

research grants from a particular drug company legitimately obtains a negative result, he could

lose funding not only for his current studies, but also parallel studies he may be conducting and

any future studies. This leads to the suppression of important negative results, and the possible


fraudulent publication of “coached” results. It is certainly in the interests of the drug companies

to prevent negative or inconclusive results from being published – by the point a study is

conducted, millions of dollars have already been spent on the development of the trial

medication. The Food and Drug Administration (FDA) has become increasingly funded by the

organizations it is designed to investigate and keep honest. More than 50% of the money spent

by the FDA reviewing and verifying effectiveness comes from the very companies who are

seeking product approval. (Moynihan) In any other profession, this would be a massive conflict

of interest. The FDA is not the only “regulatory” agency in question. In all of the medical

specialties, there are boards and committees who meet, analyze and update the definitions and

descriptions of diseases. It is apparent that if a disease has begun to manifest itself in a new and

unique way then the new symptoms must be added to the book of knowledge. The daunting part

of this system is the number of committee-serving practitioners who are not only medical

specialists, but are on the payroll of multiple drug companies, making more money than on their

regular jobs. The doctors are in an even more precarious position than either the researchers or

drug companies– their self-professed goal is never do harm to a patient. With the amount of

research going on, it is nearly impossible for a doctor to be able to stay 100% current on new

treatments and new diseases. When a disease definition is changed and the doctor believes it to

be untrue, then he is not treating his patient with the best possible treatment; if he does treat his

patient with regard to the new definition, he has ignored his own professional opinion and risked

harming the patient. The industry relies on the work of drug company employees (commonly

referred to as drug reps) to disseminate new treatments. These employees visit doctors’ offices

bearing small gifts of pens, clipboards, doughnuts… nothing unethical by anyone’s standards.


The problem is the biased, filtered information absorbed by the doctors who have to treat disease

using drugs championed by a non-medical professional.

THE RESEARCH

“We need less research, better research, and research done for the right reasons.” Douglas

Altman, British Medical Journal 1994

No one would say that we are at the apex of medical knowledge at this point in time. We

may potentially be close, or very far away – but the only way to produce new knowledge is to

conduct research. Who would be more willing to fund this research than those who stand to

profit from it? The medical research industry is huge, spending upwards of $70 billion annually

to find new products, not including clinical trials for “old” medicines and verification of previous

studies. This amount pales in comparison to the $155 billion spent annually on marketing and

administration. (Law) The beauty of science and research is the self-correcting nature of the

system; that is, when results are published, claims get tested. The only problem is the lack of

researchers verifying and confirming previous studies and results, and the abundance of those

spraying out new treatments. This is not to say there is no high quality research being done or

there is no one reviewing and confirming (or rejecting) published results. What is high quality

research? Unfortunately, it seems that is a tough question for many researchers to answer.

Medical research should completely and exhaustively establish the link (or lack thereof) between

a disease and a therapy. In order to minimize the placebo effect, control groups must be

established to determine the unexpected and difficult to explain physiological effects on the

person being tested. The gold-standard for good research is the double-blind study. The double-


blind study is designed to eliminate the effects of researcher and patient knowledge of therapy.

That is, neither the patient nor researcher know whether they are being tested with the therapy or

are being tested normal to determine the “baseline” effect. It is important that the researcher is in

the dark so that he is unable to influence observations via coaching or any other subconscious

method. Many studies are not conducted in this fashion and, in general, fail to establish a

complete, concise, and significant link between a therapy and its effectiveness. These studies

have the potential to become poster children for drug companies, as they tend to overwhelming

“evidence” in support of a drug.

The publishing of results is not the holy grail of research. It is becoming increasingly

difficult to have your research noticed by only publishing it in a prestigious medical journal –

you must market yourself and your research as a product. In order to reach the doctors (and

patients), research must be presented in the fashion of a full-on assault – marketing, seminars,

press releases and conferences, reference cards… just like a drug company marketing the next

big revelation in healthcare. This is precisely what was done by ALLHAT (Antihypertensive and

Lipid-Lowering treatment to prevent Heart ATtack). ALLHAT demonstrated that a particular

diuretic should be the first line of defense for a hypertensive patient, and, in general, the use of

older, cheaper drugs such as diuretics resulted in similar, or in some cases less, occurrences of

cardiac events compared to the more expensive drugs being marketed by drug companies, such

as ACE inhibitors. “These were not results any drug company was likely to spend millions

publicizing; buying glossy, multipage advertisements in journals; mailing out reprints;

sponsoring talks; and sending legions of detail men to knock on doors and give samples to

doctors.” (McCarthy) It is not clear whether or not this approach has been or will be effective, as

confirmed by C. David Naylor, “[ALLHAT’s campaign is] a fantastic display of medical and


academic idealism, but without the adequate machinery and support, it is going to be a bit of a

Sisyphean exercise.” The machinery and support to which he alludes is the ability of the drug

companies to spend orders of magnitude more money than researchers on advertisement.

How effective was the “largest and best attempt to compare outcomes we are ever going

to see?” (Pollack) Unfortunately, not as effective as the ALLHAT researchers would have hoped.

ALLHAT began in 1994, and published its final results in 2002; since then diuretic prescriptions

have jumped and hit a plateau (Figure 1 - Diuretic Prescription Trend). ALLHAT has been the

subject of much scrutiny on the basis of unfounded conclusions (some experts argue that some

conclusions weren’t necessarily supported by the data – correlation is not causation), biased trial

procedures (such as the prescription of an additional drug which has more synergistic benefits

with the diuretic than, say, an ACE inhibitor), and accusations of political and economic agendas

over-riding the scientific agenda of research. Diuretics are an order of magnitude less in cost than

some of the blockbuster hypertension medicines, and could have potentially saved the

government (who largely funded the study), and the healthcare industry in general, large

amounts of money. By the time ALLHAT was wrapped up and published, some of the questions

answered by the study were no longer relevant, such in the case of several of the ACE inhibitors

and calcium channel blockers becoming available in generic (i.e. cheap) form by the time of

publication (Pollack).

Ideally, researchers would be able to publish their research, regardless of outcome, in

journals for the sake of science. Any result aids the advancement of knowledge, which, unknown

now, could prove integral to another future study. More importantly, the lack of negative or no-

difference findings causes a potentially dangerous, stronger-than-reality correlation in meta-

studies. (The sounds of silence; Clinical trials) These meta-studies are simply an aggregation of


several other studies focused on the same result in order to confirm the truth of results. It is

unfortunate that negative results, which could save lives in some cases, do not get reported. It

makes sense why that is the case, though – according to the American Medical Association

(AMA), 70% of the clinical trials conducted in 2002 were funded by the pharmaceutical

industry. This is the same industry that stands well-poised to profit from publishing positive

results and censoring negative results -- sometimes massaging results into positives.

Feedback from the industry is important to the research procedure. When research is

published in a journal, there will inherently be unclear parts, misstated claims, or other generic

errors. In theory, the circulation of a magazine (some as high as 110,000 or more) should easily

catch at least some of these errors and be interested in their effects on the research and results.

Letter writing to the publishing journals is not only conducive to the scientific method, but also

functions as a peer-review. Peer-review serves an underappreciated purpose – making research

better. It is a fair bit of time that goes into writing a concise letter drenched in evidence

supporting the claim of the writer, and all too often badly linked to the original article, making

inferences and judgments difficult for readers. The difficulties in the efficacy of letters are

irrelevant when so few letters are sent to journals in response to original research. The seeming

lack of interest in peer research is profound, especially since peer-review is a considered integral

to research. (Bhopal)

Dr. Richard Smith, when Editor of the British Medical Journal, divulged some of the

tricks utilized by the industry to “fix” results (Rowan):

Avoid testing your drug against another. It might come off badly in a comparison.

Test your new product against a small group of rivals, to show that it is as good.


Compare your drug with too low or too high a dose of another treatment — so the

latter is less effective or has side effects.

Report your trial’s results only at the point when it comes out well. Publish the

helpful six-month results but bury the weak 12-month results.

Conduct your trial across a number of countries, publishing each result separately to

suggest that a huge number of trials backs your drug.

Keep republishing positive trials; the others can be buried in an obscure journal.

It seems that the drug companies go through quite a process in order to mold results into the

expected outcomes. This is because, as Dr. Smith continues, “Good results in a medical journal

are worth 1,000 pages of advertising.” The drug companies know that research is not only a

vehicle for confirmation, but is in itself advertising. In a crowded market of drugs that all

generally serve the same purpose, there must be something that sets one product apart. Clinical

trials conducted in anticipation of the market are specially designed to address potential

inadequacies in the studies of other drugs, in order to be established as the better drug, in

addition to justifying its use.

Cyberonics, a Houston-based company, has spent millions of dollars promoting its new

Vagus Nerve Stimulator (VNS) technology for the treatment of depression. VNS was approved

by the FDA for the treatment of epileptic seizures in 1997, but in 2004 the company requested

approval for the use of its device to treat depression. The FDA initially completely rejected the

request, stating “Vagus nerve stimulation therapy for depression was not approvable.” (Barglow)

Repeated tests failed to determine the efficacy of the device, and one such double-blind study

conducted at the University of Texas Southwestern Medical Center actually concluded that the

VNS device had failed to show a statistically significant difference between the placebo and


treated groups. This lack of statistical significance demonstrated that the device has no

measureable effect on depression. There were also several follow-up studies that did demonstrate

the effect of VNS therapy on depression. The only problem with these studies is patient

awareness of the device; the results were skewed because the patients knew whether the device

was turned on or not. Additionally, some patients were also receiving other antidepressant

therapy concurrently with the VNS study. (Barglow) It seems that the VNS device would be

considered ineffective and still non-approvable by the FDA. After the initial opinion of the FDA

that the device was not approvable, Cyberonics solicited a huge response from the industry and

depressed patients protesting non-approval. The FDA then assembled a review team to evaluate

the effects of the VNS for ten months. The team concluded that benefits did not outweigh risks,

and recommended again that the device not be approved to treat depression. This opinion was

discarded on July 15, 2005, when Dr. Daniel G. Schultz, Director of the FDA’s Center for

Devices and Radiological Health, approved the VNS device for the treatment of depression. This

spawned a U.S. Senate Finance Committee investigation, but still did not lead to the removal of

the device from the market. The device is still FDA-approved but is now designated as an

adjunctive treatment to be used only in addition to other antidepressant therapy. It is astonishing

that such evidence can stack up against a therapy in conjunction with such dubious behavior by

Dr. Schultz and still be considered effective treatment.

What should happen when a clinical trial produces no useful results? It should be

published in the same fashion as any other research. In the study analyzed by Diana Hackbarth,

the results did not achieve the objectives of the study – yet the publication of the study proved

useful through the thorough description and analysis of the research methods and problems

encountered in the administration of the study. (Hackbarth) This is the information that could


very easily help other researchers with similar studies. The objective should be not to produce

the desired results when the evidence doesn’t support it, but simply to increase the knowledge

base on which to build in the future. This is critical for the scientific method to work, for it is

based “on the accumulation of new knowledge through continual testing, revision, replication,

and reassessment … not sharing scientifically sound evaluations of interventions designed to

promote health, regardless of outcomes, could waste resources on ineffective treatments and

violate the public's trust in the science and the health care system.” (Hackbarth)

Clinical trials producing the desired results are only half the battle. In order to make use

of all the pseudoscientific data coming from studies, the drug companies must do everything

possible to disseminate the information to the users of the knowledge: doctors. The Lancet editor

Dr. Richard Horton describes the information-laundering operation well: (Law)

A pharmaceutical company will sponsor a scientific meeting. Speakers will be

invited to talk about a product, and they will be paid a hefty fee (several thousand

pounds) for doing so. They are chosen for their known views about a particular drug or

because they have a reputation for being adaptable in attitude towards the needs of a

company paying their fee.

The meeting takes place and the speaker delivers a talk. A pharmaceutical

communications company will record this lecture and convert it into an article for

publication usually as part of a collection offered to a medical publisher for an amount

that can run into hundreds of thousands of pounds.

The publisher will then seek a reputable journal to publish the papers based on the

symposium, commonly as a supplement to the main journal.


This is common practice in the industry. They rely on the law that requires medical professionals

(not just doctors, but pharmacists, nurses, nurse practitioners, and virtually every licensed or

certified profession that exists) to participate in a certain number of continuing education hours

(CEH) each year. The CEHs are governed by each state’s regulatory agency and can vary from

state to state. The drug companies use this to their advantage, making sure their scientific talks

are registered and qualified for CEH. These “talks” can become rather extravagant and

excessive. They range from short half-day events, to multi-day vacations to foreign lands. This is

not limited to just the medical practice and in recent years has been more regulated by the

government. (Austin) What is even more frustrating is how America’s taxpayers are partially

footing the bill – tax write-offs for doctors’ expenses while on their “continuing vacation.”

Research needs to be much less about quantity, and more about quality. It is important to

maintain not only a standard of research but a standard of learning; doctors and professionals

should not simply swallow information from a heavily biased representative, but should take the

care to review all treatments’ effectiveness to improve patients’ lives.

THE REGULATIONS

“It had long been [my] dream to make drugs for healthy people. Because then, Merck would be

able to 'sell to everyone'" Henry Gadsen, Merck CEO, Fortune Magazine 1976

This quote speaks volumes of the attitude of the pharmaceutical industry. Merck, in 1976,

was by no means a small company, and to this day is a giant – raking in over $23 billion in 2007

alone. (MERCK) A drug company makes money by selling drugs. The only way to increase that

revenue is to create more sick people, which isn’t very ethical or possible. The way to get around


that problem is simple: make new diseases for people who are healthy, or broaden the definition

of diseases to include people who may be fringe cases.

The FDA was once a tough, begrudgingly slow machine – a testament to the physician’s

creed of “first, do no harm.” It was in an interesting circumstance that the FDA began to treat

pharmaceutical companies not as adversaries (which they weren’t, necessarily), but as partners in

the fight against disease. On the surface, this seems beneficial because of the potential reduction

in bureaucratic nonsense and red tape. The caveat is a little less clear. By loosening the reins a

little bit, the FDA began to allow therapies to reach the general public which are foremost

dangerous and secondly helpful. The downward spiral began in the early 1990s, when under

political and social pressure the FDA allowed the express approval of several drugs in order to

treat what appeared to be an epidemic – AIDS. (Willman) The number of drugs approved by the

FDA is simply astounding. In 1988, the FDA had approved only 4% of the drugs on the world

market. This was a testament to thoroughness and concern for safety of the FDA. Through the

rampant approval of drugs came the express upheaval and quick showing of the lack of efficacy

of some of the drugs that made it to market. Some of these drugs (specifically 6 of the 7

mentioned in the Willman article) were never even demonstrated to exercise any life-saving

benefit. These drugs ranged from heartburn medication to painkillers, and included the now

infamous Redux. (Willman) One of the worst oversights of the FDA was the blatant disregard of

a warning not to approve a treatment for Irritable Bowel Syndrome (IBS): Lotronex.

The Lotronex saga begins with the publication of a study in The Lancet which

demonstrated positive results and noted a “safe and effective treatment for people with IBS.” As

stated previously, a study declaring something doesn’t make it truth. In this case the study failed

to mention two potentially fatal side effects which proved to be very common: severe


constipation and ischemic colitis. The latter is analogous to a heart attack in bowel, whereas the

former would become so severe that a patient’s bowel could rupture causing an abundance of

severe infections. After only 6 months on the market (following a hasty approval), doctors began

to become aware of the problems widely caused by the drug. After accessing internal FDA

documents through the freedom of information act, watchdog Public Citizen came to the

conclusion that the study published in The Lancet was not only falsely extolling the benefits of

Lotronex, but that 5 out of the 6 authors of the study were being paid by the drug company!

(Moynihan) This news shouldn’t be too astounding, as it was disclosed in the article, but it is

certainly unsettling. Not only were the results of the study being interpreted by researchers who

were inclined to producing a specific result, but the raw data from the study showed that the drug

was only slightly more effective than placebo. In light of the situation, several pushed for the

withdrawal of the drug from the market by the FDA. The FDA defiantly refused, calling requests

for withdrawal “drastic.” The company (GlaxoSmithKline, GSK) later voluntarily withdrew the

drug from the market in light of “mounting evidence of dangerous side effects, negative media

coverage and a regulator apparently unable to ‘determine a course forward.’” (Moynihan)

Lotronex is still on the market today, and is the only drug to be reapproved by the FDA after

withdrawal from the market. In order to prescribe the drug, doctors must be enrolled in the

Prometheus Prescribing Program (Prometheus Therapeutics and Diagnostics). It is advised that

the drug only be prescribed in cases of severe and chronic cases of IBS.

The Lotronex fiasco all began with the issuance of regulations designed to “[give] the

FDA discretion to ‘accelerate approval of certain new drugs’ for serious or life-threatening

conditions” (Willman) and the passage of a congressional bill that set goals for the FDA to


approve drugs within 6 months to one year. This was all done in an effort to get life saving drugs

into the hands (mouths) of the American people. The road to hell is paved with good intentions.

In yet another attempt (successful, I might add) to get more drugs in the hands of more

people, doctors and committees (who are, usually, in collaboration with drug companies) have

begun broadening the definitions of diseases, or adjusting the thresholds of risk factors required

to diagnose a particular condition. It is important to note that a risk factor is not a disease in and

of itself. Cholesterol, the numbers with which so many middle-aged men and women are

concerned, is simply a risk factor. Having high cholesterol does not mean you are destined to

have a heart attack; the fact that you smoke, eat fatty foods, and watch Sportscenter 7 days a

week does. It is the combination of several risk factors that leads to the proper diagnosis of

disease. This is not refuting the correlation of cholesterol levels to coronary heart disease (CHD),

but simply reinforcing that an apt diagnosis should not be based on a single number, but instead

on a careful observation of the tendencies of a patient to engage (or more importantly, not

engage) in activities which also increase the risk of CHD. An interesting note on cholesterol: it is

the most common organic molecule in the brain and there is an established link between statin

therapy (more on statins in a minute) and their “small but statistically significant negative effect

on cognitive function.” In 2001, as part of the National Cholesterol Education Program, an

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults

(Expert Panel, herein) updated guidelines for reducing the risk of developing CHD reflecting the

most recent rounds of clinical trials. These recommendations included increasing the number of

Americans taking statins from 13 million to 36 million. The basis for increased statin therapy

was the drugs’ ability to reduce cholesterol and, based on cholesterol’s link to increased risk of

heart disease from as far back as 1948, CHD. After the publication of these new guidelines, it


would be almost unthinkable to conduct a study comparing the old, out-dated, and potentially

not-the-best-available treatments to the newer standards for treatment. That is exactly what

ALLHAT did beginning in the early 1990s, much before the publication of the new guidelines. It

is noted that ALLHAT results showed that, among other things, tripling the number of people on

statins neither prevented heart disease nor decreased the overall risk of death. (Abramson) What

is important here is the lack of review and regulation of drugs and guidelines (by the FDA or

others) to prevent the pseudoscientific reasoning behind arbitrarily modifying diagnosis

guidelines for disorders.

Cholesterol is not the only culprit in this case. Bipolarity, formerly referred to as manic-

depression, has “reached epidemic proportions”, and is being chalked up to softening criteria for

diagnosis. (Bobby) Bobby goes on to hit the nail on the head:

Just as a child with a hammer discovers new things that “need” to be hammered, when

psychiatry finds new drugs it discovers new people who “need” to be treated with them.

This has been also noted with the introduction of lithium as a treatment for bipolarity in the

1960s. Two arguments could be made here: we now know more concisely what the disorder is

and more accurately how it manifests itself and are, therefore, treating more patients; or, that we

have reduced the severity and frequency of symptoms and are catching more people. Formerly,

criteria for the diagnosis of bipolar disorder included hospitalization for a manic episode, with

estimated rates of bipolarity being between 0.4 and 1.2 percent of population. It is now estimated

that as much as 10 percent of the population is bipolar, while the rates of manic episode

hospitalizations have not increased. An explanation for this is the “hammer theory” mentioned

above. (Bobby)


Thanks to the information age, it is becoming easier for people to self-diagnose (which

could also be a potential problem), but also confirm that a diagnosis does seem reasonable. The

patient should be aware of what he is taking, and not just take the word of the doctor, drug

company, or FDA.

THE DOCTORS

It should never be the obligation of the patient to ensure correct treatment, but rational

people would agree that you shouldn’t take the current AIDS cocktail if you don’t have AIDS. It

is easily one of the most unethical and just plain wrong things a doctor can do – knowingly

administer an unjust treatment. Are the doctors to blame if they are being blasted with new fad

treatments and biased research information and are under the belief that their treatments are the

most effective and best available? Absolutely. Doctors are obligated to do no harm to any of

their patients. In order to adhere to that standard, they must not treat blindly with the therapies

that have been handed to them. Doctors should be more responsible for their prescriptions and be

more willing to engage in active learning that supports their practice and dedication to life-long

learning. There are multiple therapies which, before approval, were at least as dubious as

rejected ones – yet they somehow became mainstream treatments, which in some cases reached

epidemic proportions. It is the responsibility of the practitioner to screen all patients well and to

be absolutely positive that any symptoms are proof positive of a diagnosis. There does not need

to be a treatment for every human, but a treatment for every human with a disease.


OUTLOOK

In order to fix the problem at hand, a major renovation of the system is necessary. It is

important that we continue to produce new knowledge, especially in a scientific fashion which is

conducive to making sick people healthy. Of course drug companies are going to be involved in

the research process; that connection is inherently inseverable. It is critical that the link between

drug companies and researchers be academic and not business oriented. It is important that we

have people conducting research who are adequately prepared and able to perform it. As Altman

says, “poor research arises because researchers feel compelled for career reasons to carry out

research that they are ill equipped to perform, and nobody stops them.” At some point in their

careers, most doctors will be required to conduct some form of research with the intention of

publication. Why is it that with career ambitions of research a doctor must publish? It is certainly

not an direct measure of proficiency, nor is having 100 more papers than another doctor an

indicator of superiority. It simply looks good, and in theory gives the doctor some experience in

the production of research which could help him in the interpretation of research. This is true

when conducting a well-designed sensible trial, but certainly not the case when involved in an

egregious study designed to produce results and not test hypotheses. (Altman) Ideally, the

medical metric of publications needs to be abandoned. It is apparent that the number of papers is

irrelevant given that so many of them could be poorly designed studies that were badly executed.

The only way to stop the downward spiral is to be aware of the existence of bad research and the

possibility of bad treatments, be healthily skeptical of things which just sound too good to be

true, and to hold those who you think have a higher standard to a higher standard.


It is important to notice that the medical industry as a whole is a modern technology

which has and will continue to increase the quality of life for many people. For a majority of

cases and situations, there is no gray area – a broken leg will always need to be set and

immobilized. There is generally no limit of the amount of money people will spend on their

health, which is why there is such a strong push to insure every possible problem is diagnosable

and treatable. A lot of trust in placed in the medical profession, yet sometimes those steering the

field are doing it for the wrong reasons. Everybody in the profession should take it upon

themselves to personally insure they are conducting the best possible practice that is concurrent

with science. Whatever you do, be able to prove it.


Figure 1 - Diuretic Prescription Trend


BIBLIOGRAPHY

Abramson, John. Overdo$ed America. New York: HarperCollins, 2004.

Altman, Douglas G. "The scandal of poor medical research: we need less research, better research, and research done for the right reasons." British Medical Journal (Jan 29, 1994): 283.

Austin, Elizabeth. "Continuing Vacation - taxpayers sibsidize continuing education." Washington Monthly November 1995.

Barglow, Peter. "Corporate self interest and Vagus Nerve Stimulation for depression." Skeptical Inquirer Sept-Oct 2008: 35-41.

Bhopal, R.S., and Alison Tonks. "The role of letters in reviewing research." British Medical Journal (1994): 1582.

Bobby, Stephen Ray Flora and Sarah Elizabeth. "The bipolar bamboozle." Skeptical Inquirer Sept-Oct 2008: 41-46.

Hackbarth, Diana. "Research reporting and evidence of effectiveness: why "no difference" matters." American Journal of Critical Care (May 2008): 218.

Law, Jacky. Big Pharma. New York: Carroll & Graf, 2006.

McCarthy, Michael. "Researchers try marketing techniques to sell their results: trial investigators say publishing results not enough to change practice." The Lancet (2003): 1204.

MERCK. MERCK 2007 Annual Review. 04 March 2008. 6 October 2008 <http://www.merck.com/finance/annualreport/ar2007/pdf/merck-ar-MAR.04.08.pdf>.

Moynihan, Ray and Alan Cassels. Selling Sickness: How the World's Biggest Pharmaceuticals Companies Are Turning Us All into Patients. New York: Nation Books, 2005.

Pollack, Andrew. "The Minimal Impact of a Big Hypertension Study." New York Times 27 November 2008.

Prometheus Therapeutics and Diagnostics. Highlights of Prescribing Information. April 2008. 6 October 2008 <http://www.lotronex.com/PDF/us_lotronex.pdf>.

Rowan, David. "The hookers." The Times 25 October 2004.

"The sounds of silence; Clinical trials." The Economist (US) 11 September 2004: 75.


Willman, David. "How a New Policy Led to Seven Deadly Drugs." Los Angeles Times 20 December 2000.


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