The Bayh Dole Act and the fate of research

While researching information for my Ethical and legal issues in Biomedical writing class on the Indian version of the American Bayh Dole Act, I came across a very interesting article which I would like to share with you.

The article can be found at: http://money.cnn.com/magazines/fortune/fortune_archive/2005/09/19/8272884/index.htm

The article makes for very interesting reading and touches on many different incidences and issues.

The article talks about how the Bayh Dole Act , which was passed in 1980 in the United States, wasn't looked upon as the savior of the fate of federally funded research in the United States. The Bayh Dole Act basically allowed grantee institutions conducting research with federal funds to patent and commercialize their inventions. Prior to the Bayh Dole Act federally funded inventions belonged to the government and a very few of these inventions ever reached the public.

With regards to the implementation of a version of the Bayh Dole Act in India, I have been asking myself many questions over and over again:

Will innovation be hampered if universities are allowed to patent, commercialize, and basically make money off of their inventions created with federal funds?

WIll it hamper basic scientific research?

Will it create a uncontrollable rat race amongst scientist in universities?

So many questions, but I haven't yet come to a conclusion in spite of weeks of research, questioning, pondering, and deliberation.

Moral Complicity

In searching the Internet for medical-oriented ethics organizations, I found the website for the American Academy of Medical Ethics (AAME). AAME's mission: "...to promote the interests of medical educators, medical practitioners and scientists, and to protect and promote the historic values that have provided the long-standing foundation for western medical care".

On AAME's website, I found the following article on moral complicity: http://cbhd.org/content/addressing-issues-moral-complicity-when-where-why-and-other-questions. The article poses many interesting questions that I'm not sure how to respond to. For example, should physicians take advantage of findings from research that they know was obtained under unethical conditions but will help their patients? The author, Robert Orr, MD defines moral complicity by using this example: Does person B (in this case the physician who uses the data) have any moral culpability by associating with the actions of person A (in this case the person who conducted the unethical research)?

Timing is important in determining moral complicity. If someone knows ahead of time that an unethical act is about to occur that they will later benefit from and they facilitate the unethical act in happening, they are morally complicit. Another factor in deciding if a situation is morally complicit is proximity. Orr discusses the example of someone who washes the windows of a medical office where abortions are performed. Wouldn't this person be less complicit than the doctor who actually performs the procedures? In all, Orr identifies 5 factors that should be examined to determine if a situation is morally complicit.

This article made me wonder how moral complicity coincides with, or differs from ethics? Are they the same?

Acres of Skin

In Acres of Skin (1998), Allen Hornblum discusses the experiments conducted on prisoners at Holmesburg Prison from the 1950's until the experiments ended in 1974. Unlike the subjects in the Tuskegee experiment, the prisoners were not exclusively African-American. Also unlike the Tuskegee trials, the Holmesburg Prison experiments did not focus on sexually transmitted diseases, but focused on dermatological experiments. Albert Kligman, MD was the dermatologist supervising the studies and shockingly likened the prisoners' skin to acres of fertile farmland. Prisoners were exposed to radioactive elements, hallucinogenics, and other toxins while Kligman tested various drugs, including what would become Retin A. For years after the experiments ended, prisoners still suffered from exposure to these chemicals.

In doing a Google search of Dr. Kligman, I found that he is on the faculty as Professor Emeritus at the University of Pennsylvania. He received his medical degree from Penn in 1947. "Contact sensitization" is listed as one his specialties, along with "cutaneous toxicology".

In interviews after the experiments at Holmesburg ceased, Dr. Kligman continued to defend his practices. In 2006, renewed interest in using prisoners for research resurfaced. Supporters proposed that the 1978 regulations forbidding the use of prisoners in clinical research be repealed but that the government add safety measures to prevent abuses. Dr. Kligman is quoted as saying that regulations that restricted prisoner use in clinical research "should have never been written in the first place" because of the gains that the research provided to the general population.

Where do we draw the line between achieving greater good and abusing individuals who are incarcerated, marginalized, or without representation?

Enrolling Ineligible Patients in Trials

I was not aware that physicians violate clinical trial enrollment criteria by allowing unsuitable patients to participate in trials.

In the 10/29/09 New York Times, Pauline Chen, MD writes about her ethical concerns that arose from wanting to enroll a very sick patient in a clinical trial. Dr. Chen explains that her patient, who was diagnosed with liver cancer and only had 3 months to live, just wanted to live long enough to see her first grandchild be born. Dr. Chen begins to think about enrolling the patient in a clinical trial for an experimental drug.

The article goes on to explain that many physicians are faced with this ethical decision: to maintain study enrollment criteria and protocol and therefore obtain information that can be generalized for all patients or to violate study rules by focusing on improving the health of one patient. If physicians do allow patients to be enrolled in clinical trials by not disclosing how sick the patient really is, not only are patients harmed, but the trials can be as well. In a survey of 700 physicians published in an bioethics journal, 90% responded that they are alright with violating trial enrollment criteria if a patient could benefit from the trial. Also surprising is that more than 60% of physicians said that they would break study rules to help a patient.

Findings indicate that the value of the relationship between the patient and physician is still high; physicians are willing to violate medical ethics to retain the patient-physician bond and help patients live longer, even if they may ultimately die from an uncured illness. Dr. Chen's patient was provided with the study drug without enrolling in the trial and she lived long enough to become a grandmother, dying a few days later.

This article and study further call into question clinical study results and medical ethics. Link to article: http://www.nytimes.com/2009/10/29/health/29chen.html

Top 10 False Claims Act

Top 10 False Claim Acts

Under the False Claims Act, 31 U.S.C. §§ 3729-3733, those who knowingly submit, or cause another person or entity to submit, false claims for payment of government funds are liable for three times the government’s damages plus civil penalties of $5,500 to $11,000 per false claim.

This act allows citizens with proof of fraud having been committed against the government to sue, on behalf of the government. These whistleblowers are compensated between 15 to 25% of the funds recovered by the government.

I thought that it would be interesting to see the amounts that have been paid back to the government due to the False Claims Act. Here is a list of the top 10 false claims:

Company	Amount	Date
Pfizer	$1,000,000,000	September 2009
Tenet	90,00,00,000	July 2006
HCA	73,14,00,000	December 2000
Merck	$650000000	January 2008
HCA	$631000000	June 2003
Serono Group	$567000000	October 2005
TAP Pharmaceuticals Products Inc	$559483560	October 2001
New York State and New York City	$540000000	July 2009
Schering Plough	$435000000	August 2008
Eli Lilly	$438000000	January 2009

I just thought it would be interesting for us to know about to what extent the government recovers money lost due to health care fraud.

The top 100 false claim act cases can be viewed at : http://www.taf.org/top100fca.htm

Wyeth Vs. Levine

For those of you who haven’t read about the Wyeth v Levine case, here are two links.
Wyeth Loses Preemption Battle and The Facts—Wyeth Vs. Levine
There are a lot of issues to be addressed in this case, I do realize that. My main issue is with the fact that Wyeth wanted to change the labeling on Phenergan regarding intra-arterial administration of the drug, but the FDA specifically asked them to retain the language on the label. In the end, Wyeth was sued by Diana Levine for not including appropriate information on intra-arterial administration of Phenergan. For once, I believe that the drug company isn’t at fault. The FDA, the body that regulates drugs in the United States, asked Wyeth not to make changes in their label. And they get sued for not making changes!
Not being a lawyer, I’m sure I don’t understand the case as well as a lawyer would, but I am truly bewildered by the thought that the FDA would ask a drug company to not include a warning when that drug could be potentially harmful.

FDA and the Declaration of Helsinki

The Declaration of Helsinki renders protection to human subjects in clinical trials. It gives a set of ethical guidelines to follow while conducting clinical trials involving human subjects.

The Declaration isn’t so much a law as it is a set of guidelines. But, in the global scenario countries do tend to stick to these guidelines and not violate them.

But not the FDA.

In April of 2009, the FDA issued a statement saying American trials conducted outside the United states would no longer be required to adhere to the Declaration of Helsinki. This also means that pharmaceutical companies can use placebo instead of the current standard of medical care as the control.

Why would the FDA do this? The United States conducts clinical trials in so many countries including developing countries such as Brazil, India, China, and so many African countries.

The people in these countries may not necessarily be educated, literate, and many may not be able to understand the details of the informed consent form. But, they would still agree to participate in the trial because of the compensation they receive, however menial it is.

These underprivileged people are easy targets for unethical practices of the pharmaceutical companies.

Also, using a placebo instead of a comparable treatment may lower costs of the trial, but the trial is not being conducted with scientific integrity. Results of these trials wouldn't give us clear idea of the effects of the drug being tested, because the drug is being tested against a placebo (=nothing)!

Shouldn’t the FDA ensure that these people are protected in the same way that Americans participating in trials are? Aren’t all people equal?

Look what happened with Pfizer in Nigeria. Does the FDA want the blood of innocent people on it’s hands?

Cancer drugs, patients, and the FDA: Where do we go now?

To

I read an interesting article in the New York Times a few days ago (Where Cancer Progress Is Rare, One Man Says No. September 15th, 2009), which talks about the possibility that the FDA is over-regulating cancer drugs.
Reading the article got me thinking: When dealing with a disease like cancer, which in many cases is fatal, should the FDA be more lenient while approving drugs to treat cancer? The rationale behind this is that, people who have cancer already suffer from the terrible manifestations of the disease, so what’s the harm in giving them drugs which may have terrible side-effects and which may or may not cure their disease? To these patients or to their families, they have nothing much to lose.
My take on this:
The FDA is one of the most reputed regulatory agencies in the world. It has certain standards that it adheres to, no matter what. If the FDA started approving drugs, just because these drugs treat terminally ill people who may not live in any case, the agency would lose its credibility. Why should the FDA single out only cancer patients? Can’t an extremely obese people ask the FDA to approve drugs that help you slim down, even if these drugs may wreck havoc on the liver and kidneys? What about Alzheimer’s patients? They are generally headed down a dead end street. My paternal grandfather has a condition very similar to Alzheimer’s. I would love for regulatory agencies to say: Well, these people have nothing to lose. Let’s just approve the drug and hope for the best. No, it doesn’t really work that way.
The other drawback is that, if the FDA were to approve these drugs and if something went wrong, as with Rofecoxib, Nimesulide, or Thalidomide, nobody would remember that the FDA approved these drugs(I’m talking about hypothetical drugs which could be approved in the future because of pressure from patient advocates) because of public pressure. The outcome of this would be lawsuits, lawsuits, and more lawsuits.
The FDA may not always make the best of decisions but on this subject I stand by them.

Ghostwriting and Ethics

Many industries, including biography publishing and even rap, employ ghostwriters without significant concerns. However, the use of ghostwriters in medical writing has raised ethical concerns. The medical industry uses ghostwriters to edit, revise, and polish the writing of physicians and scientists whose writing may not adequate convey ideas clearly.

First, one must ask how pervasive the practice is in the pharmaceutical industry. In an August 5, 2009 article in the New York Times, Joseph Ross, MD said referring to ghostwriting: "It's almost like steroids and baseball. You don't know who was using and who wasn't; you don't know which articles are tainted and which aren't".

Does ghostwriting determine scientific integrity? The most vocal critics say that research findings can be skewed by contributions from writers who are employed by pharmaceutical companies and don't disclose these relationships. A September 18, 2009 NYT article explains that the editors of Blood determined that a pharma employee had contributed significant portions to an article published under the name of prominent researcher. The editors believe that the ghostwriter should have been listed an author, and not merely listed in the acknowledgments as was the case. In another case, Wyeth employed ghostwriters to down play the risk of hormonal therapy for menopausal women. Articles were published in 18 well-respected medical journals between 1998 and 2005. Later research uncovered the truth: the therapy caused an increased risk of breast cancer, heart disease, and stroke.

Who loses in these scenarios? Wyeth's revenue rose to almost $2 billion from sales of Premarin and Prempro. It is not clear if Wyeth's reputation suffered as a result. Women taking these medications were certainly losers. Experts also agree that medical research as a whole suffers. Jeffrey Francer of the Pharmaceutical Research and Manufacturers notes that ghostwriting transgressions and the resulting restrictions put in place by journal editors to identify ghostwriters could "chill research and chill support for research". So we all lose.

What solutions exist? Journal editors and legislators are pushing for requirements that require lead authors disclose all other contributors or risk being barred from writing for academic journals for an indefinite time period. Other journals no longer publish "opinion" or editorial articles from writers who have ties to pharmaceutical companies.

Ghostwriting in the pharmaceutical industry is pervasive and fulfills a necessary role. However, relationships to drug manufacturers should be disclosed and should not stop negative information about drug side effects from being published.

Outsourcing clinical trials : A big pain, but is there much gain?

Clinical trials are now moving to countries all over the world: China, Kenya, India, Tanzania, Nigeria, and everywhere else!

From the economical standpoint, conducting a clinical trial in one of these developing countries is relatively cheaper than conducting them in developed countries in North America, Europe, or Australia.

But the more compelling reason to outsource clinical trials is to test drugs on a diaspora of people, people with different genetic make-up, as well as to test drugs for diseases such as malaria, HIV, meningitis etc, which are more common to these developing nations.

But outsourcing clinical trials is not as simple as packing up your bags, getting onto a plane, and jetting off to a foreign land.

Clinical trials outsourced to developing countries are watched by IRB’s and regulatory agencies with the same level of scrutiny (if not a higher level) as those conducted in developed countries. In fact, various reports say that it’s tougher conducting trials in developing countries because of the ethical and legal guidelines that have to be followed.

I believe that informed consent in outsourced clinical trials would be a difficult task because the researchers would have to factor in cultural characteristics while preparing informed consent forms and while talking to clinical trial subjects. It also would be a problem when dealing with an illiterate or uneducated population, in which case simple language and efficient translation wouldn't be of much use.

The Declaration of Helsinki renders protection to human subjects in research who are underprivileged. Thus, IRBs and regulatory agencies have to ensure that these subjects are not being mistreated. The IRB from each participating institution/company needs to approve the clinical trial protocol. So very often you're stuck waiting for IRB approval from a dozen different institutions! How does this make a clinical trial more ethical or even ethical, for that matter???

I understand the need for an ethical and protocol review by an IRB. But, why can't just one IRB do the job?

Just a suggestion, but maybe they could have one IRB on behalf of the participating institutions and one local IRB. It would make things easier, speed up the trial, and save a lot of money.

Ok, so outsourcing clinical trials isn't the easiest task in the world. But what happens after you get IRB approval? After you begin the trial?

I'm sure that many of these trials are successful and offer the people of these countries a chance to receive possible life-saving drugs. But are these trials conducted ethically? A 100% ethically? Having lived in both India and Africa I can't help but imagine a lot of money hungry officials looking out for a quick buck in exchange for speeding up the process locally. I somehow can't believe it's all smooth sailing after IRB approval.

What do you all think?

Ethics and the Big Pharma

The pharmaceutical industry hasn’t been shown in the best of light over the years. The media has always portrayed Big Pharma as the ‘bad guys’, the villains, the wrong doers...

Is this a case of the media hyping an issue that isn’t as bad and far-fetched as it’s presented to the public?

Well, in my quest to answer this question I spent a few hours on the internet looking up what Big Pharma has been up to.

I’m sharing with you a little bit of what I found. (Prepare to be shocked)

1)During 2003 to 2004, Merck and Co payed the Australian branch of the publishing giant Elsevier vast sums of money to print a ‘fake journal’ for them. This journal mostly contained reprinted articles, about Merck drugs and Merck studies, which showed the company and it’s products in a favorable light. Many of the articles were to do with the osteoporosis medication Fosamax and the infamous killer NSAID Vioxx.

In no article was there a mention that the journal and articles were sponsored by Merck.

What’s wrong in this,one may ask? These articles showed the company and it’s products in a positive light at the same time ignoring the possible dangers of their drugs. The journal was basically a marketing tool for the company. When publishing articles about a drug, the negative aspect of the drug cannot be ignored.

2) In 1996, Pfizer tested an experimental antibiotic Trovan on children in Nigeria. 11 children died after using the drug and 181 other children developed brain damage and arthritis. Trovan was tested on 200 Nigerian children at so-called epidemic camp (there was a meningitis epidemic in Nigeria at the time) in the city of Kano in Nigeria.

Pfizer, in a total violation of all sorts of international laws and ethical guidelines, did not obtain informed consent from the 200 subjects before administering the drug. The parents of these children were not informed that they could opt for their children to be treated with meningitis medication which had already been tested. Pfizer claims that the parents of these children were well aware that their children were to receive the drug. Trovan was banned by both the FDA and the EU in 1997 after reports that it caused liver damage.

This July, Pfizer reached a $75 million settlement with the Nigerian authorities.

3) Something even more shocking:

Merck developed a ‘hit-list’ of doctors who were not pleased with Merck’s drug Vioxx. These doctors were supposed to be ‘neutralized’ according to e-mails sent by Merck employees to each other.

As we can see, the media isn’t totally wrong. Lack of disclosure while publishing articles, absence of informed consent during clinical trials, targeting a vulnerable population during clinical trials, and planning to ‘neutralize’ doctors for not liking your drug....well it’s illegal, unethical, and plain wrong.

Big Pharma does save lives by making life-saving medication, but it somehow doesn’t even begin to compensate for their other activities.

Introduction

This is the first of a series of blog posts relating to pharmaceutical law.