Follow-up to the March 29 letter on Schering-Plough study P03659 (NCT00160251)

Yesterday afternoon, I participated in a conference call with four representatives of Schering-Plough. They initiated the call after reading my open letter to Schering-Plough of March 29th. This post is not a letter, but a follow-up based on the information gathered in that conference call.

I talked with Ken Banta, Director of Strategic Communications, Robert Consalvo, Media Contact for PEG-Intron, Cecil B. Pickett, PhD, Senior Vice President and President, Schering-Plough Research Institute, and Robert J. Spiegel, MD, Senior Vice President, Medical Affairs and Chief Medical Officer. They addressed my questions, and gave me a clearer understanding of their rational for this study design. Although I still have some concerns about the study design, I was pleased that they were willing to talk with me about the protocol. Here are some of the questions I raised and the answers I received:

* How is "African-American" defined in this trial? Those who define themselves as "African-American" are considered "African-American". A patient can designate themselves as she wishes. It is important to note that several studies have shown that a higher percentage of those who self-identify as African-American are non-responsive to the standard HepC treatment (pegylated interferons and ribavirin) as compared to European-Americans. Schering-Plough acknowledged that the lack of a biological or other measurable means of defining population groups introduces complications in interpreting and applying these data.

* Can people of African-descent participate is this trial if they do not identify as African-American? Apparently so.

* Are African-Americans banned from this trial in an effort to increase genetic homogeneity? "That would be absurd." No, that is not the rationale.

* Are African-Americans banned from this trial because some studies have shown that African-Americans have lower neutrophil counts? No, neutrophil counts are very important when ribavirin is used, but ribavirin is not used in this trial. In addition, neutrophil counts are an inclusion criteria.

I asked if there were specific scientific or safety reasons for excluding African-Americans from this trial. I was not satisfied with their answers even though they were framed in the language of safety and science. For example, since we do not yet know if African-Americans (as a group) will show similar response rates to SCH 503034 as they do to the standard treatment, it seems that they should be included in the trial unless or until safety or scientific concerns suggest otherwise. Also, thorough and ongoing informed consent procedures would ensure that African-American study participants (and all other study participants) are aware of the risk of non-responsiveness over time or at higher doses. It is important to note that I have not reviewed the full protocol for this study. There could be clarifying information in that document, but that information, if it exists, was not conveyed to me during the conversation with Schering-Plough.

My interpretation is that since some studies have shown that African-Americans (as a group) respond differently to the standard HepC treatment (as compared to European-Americans, what about other ethnic groups?), it is more expedient to exclude African-Americans from the low-dose arms of the Phase II study of this new interferon based therapy. (African-Americans will be included in Phase III as mandated by law.) It seems they think this will make the data 'cleaner', but that comes at a cost to African-Americans who could potentially benefit from the low-dose drug in the trial, and it prevents researchers from studying the mechanism and effects of this drug in this population group. (Schering-Plough is currently running a separate single-dose clinical pharmacology study in African-Americans to partially address the latter concern.) It seems they feel they will save time by excluding African-Americans now. By their rationale, all people with HepC will receive a greater benefit if they can bring the drug to market sooner. In addition, Schering-Plough will be able to make money sooner.

Others, particularly the HepC and HIV advocacy groups from whom I first heard about this trial, contend that Schering-Plough's assumptions (African Americans will be more resistant to this drug, excluding them will save time, etc.) may not be correct, and that people's lives hang in the balance now. Given the information I have, I agree with this position.

My current research focuses on ethical and scientifically-responsible uses of race in biomedical research. The information I have suggests that this is not an ethical or scientifically-responsible use of race. As I noted in the original letter, defining 'race' is a complex issue that cannot be accomplished using only biological or scientific means. That makes the concept of 'race' particularly difficult to use in biomedical research, especially since it is a very real social concept that correlates strongly with certain health indicators. It is my position that this study, like many others, misuses the concept of 'race'. Fixing this problem requires a systematic and scientifically and socially-informed change in the way we understand, define and use race. Given yesterday's conversation, I hope that Schering-Plough will be on the leading edge of this change, if for no other reason than it will allow us all to produce better quality scientific and medical data that can be more easily and appropriately applied to individuals and population groups.

Let me express my gratitude again to the Schering-Plough representatives for talking with me about this issue. We may not agree on the immediate solution, but our conversation has helped advance my thought on this complex and important issue. Thank you.

Questions on the exclusion of African-American patients in study P03659 (NCT00160251)

An open letter to Schering-Plough:

I am writing to inquire about the study design of your phase 2 trail of the drug SCH 503034 in combination with PEG-Intron in adult subjects who have chronic hepatitis C without cirrhosis. According to clinicaltrials.gov, this trial excludes, among others, "patients with cirrhosis, co-infection with Hepatitis B or HIV, and African-American patients." As a geneticist and bioethicist, I have difficulty understanding why African-American patients are being excluded from this trial, particularly since that is the only ethnic group specifically excluded.

Excluding African-Americans will not lead to greater genetic homogeneity as 85% of genetic diversity is found within population groups. In addition, genetic, anthropological and other data show that individuals and populations vary along worldwide gradients rather than clustering into distinct "races."

Social and biological scientists have raised numerous concerns about the difficulties faced in defining a particular ethnic group, with "African-American" being particularly contentious. How are you defining "African-American" in your trial? How does your definition relate to the medical and biological phenomena being studied in the trial?

If you are excluding African-Americans for social or other nonbiological reasons, it would be useful to specifically define those exclusion criteria. That information could be used to exclude non-African-Americans who do meet the exclusion criteria, and include African-Americans who do not and otherwise qualify. Does your full-length protocol define such criteria for which 'African-American' is presumably used as a proxy? If so, are there reasons why this information is collapsed into the term 'African-American'?

The National Institutes of Health Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research states that

"women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification establishes to the satisfaction of the relevant Institute/Center Director that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research."

Although your work is not supported by the NIH, I and others would like to know your compelling reason for excluding African-Americans.

Given the benefits and risks associated with participation in clinical trials, it is critical that only relevant criteria are used to exclude and include participants. I have called the Schering-Plough office at 908-298-7409 to raise these questions and concerns and look forward to your prompt reply. Thank you for your assistance in this matter.

Sincerely,

Karama C. Neal, PhD MA

'photographic' art

Dear Ms. Tuck,

I was disappointed that the AJC choose to create and use the 'photograph' of Jeremy Jones that accompanied the article, "The Life of a Killer" (December 4, 2005, A1). Photo manipulation of the type seen on Sunday's front page detracts from the reporting and writing it accompanies. In addition, its sensational nature lessens the reputation of the AJC. Finally, it is a small step from the Jeremy Jones 'picture' used by the AJC to the sort of regrettable and offensive photo-manipulation done by TIME magazine to the OJ Simpson's mugshot for its cover (see en.wikipedia.org/wiki/Image:OJ_Simpson_Newsweek_TIME.png).

Good reporting, good writing, and good photography will stand on their own, and do not need to be accompanied by such "art" to make their point. Please reconsider the use of such images.

Thank you for your time and thought on this matter. I continue to read and enjoy to the AJC.

Sincerely,

Karama Neal

What do child smugglers look like?

Dear Ms. Borden,

I read with interest your article on the Smyrna woman involved in child smuggling. It was particularly intrigued by your first sentence, and wonder, what exactly a child smuggler looks like. I assume "Goforth didn't look much like a child smuggler" was written without malicious intent. However such phrasing implies that there are people who look like child smugglers (people who presumably do not have blue eyes, among other things) and reinforces stereotypes against such people. I hope that you will reconsider the use of that phrase. Thank you for your otherwise excellent article.

Sincerely,

Karama Neal

"Race" does not determine biology (and vice versa)

To the editor (Atlanta Journal-Constitution):

The research leading to the discovery of a gene variant the increases the risk of heart attack is to be commended (Gene find links race, heart risk" AJC 11/11/05 Pg A1). However, physicians and others who apply this research must remember that given the high levels of genetic variation within population groups, and the large amounts of ethnic admixture that continue to exist in the US and elsewhere, many people who self-identify as African-American may not carry the gene variant and have no increased risk of heart attack. Likewise, those who do not identify as African-American may well have the version of the gene that raises risk of health attack.

Though race and ethnicity remain important and relevant social phenomena, decades of biological research offer no evidence of a biological or physical basis for race. For that reason, it is critical that scientists and physicians focus on measurable, medically-relevant factors and avoid making assumptions about genetics or health based on race or ethnicity.

Karama C. Neal, PhD

Darfur Peace and Accountability Act of 2005, S. 1462, H.R. 3127

Dear Sen. Chambliss, Sen. Isakson, Rep. McKinney,

I am writing to ask that you cosponsor the Darfur Peace and Accountability Act of 2005, S. 1462/H.R.3127. This legislation would help expand and strengthen the African Union mission to better protect civilians, impose focused sanctions on individuals responsible for atrocities in Darfur, and support peace negotiations to resolve the conflict.

Numerous Sudanese people live near my church in Decatur, and a group of them spoke there recently. Their descriptions of life and death in Darfur encouraged me to act in support of this bill. I hope you will lend your support as well.

The crisis in the Darfur region of Sudan has received very little attention in recent months. Yet, security for the people of Darfur is not improving. Uncontrolled militias and rebel groups continue to attack civilians, harass humanitarian workers, beat and rape women and girls, and block delivery of critical aid supplies. Hundreds of thousands of people have been killed, and over 2 million people remain displaced by the ongoing violence. Drought and famine threaten millions of desperate people already suffering under the continuing genocide.

The U.S. and the international community must do more. I urge you to add your name as a cosponsor to the Darfur Peace and Accountability Act of 2005 (S. 1462/H.R.3127). Please let me know what your decision will be in this regard, as I’d like to pass that information on to others in my community. I look forward to hearing your response.

Sincerely,

Karama C. Neal

Use of biodiesel and WVO/SVO

To the editor,

Truckers and others who are "scrambl[ing] for diesel fuel" (September 29, 2005, E1) may want to consider the diesel alternatives described in the September 22 AJC ("High gas prices grease path for vegetable oil fuel option"). Biodiesel and waste vegetable oil are readily available, energy efficient, sustainable, less toxic, and often less expensive than diesel. In addition, use of these fuels decreases our dependence on foreign, nonrenewable oil, and contributes to our agricultural development and national economy.

In 1911, Rudolf Diesel, inventor of the diesel engine, said "The use of vegetable oils for engine fuels may seem insignificant today. But such oils may become in the course of time as important as petroleum and the coal tar products of the present time."

In this time of fuel shortages and rising prices, it is critical that we consider all our options for fueling our vehicles and fueling our economy.

Karama C. Neal

1% For The Planet: GreenKarat and MedShare International.

Dear Matt,

Thank you so much for the wonderful and much-needed work you are doing at GreenKarat. My husband and I wear GreenKarat wedding rings, and we value the opportunity to choose rings that are environmentally responsible and conflict free.

Thank you also for your participation in 1% For The Planet. As a citizen of the earth, and African American woman, and a bioethicist, I am particularly concerned with issues of environmental justice and health. MedShare International works toward environmental and biomedical justice by distributing unused medical supplies from the US to hospitals and clinics around the world that can use them. This decreases biomedical waste in the US, reduces landfill contributions and helps all people have access to good medical care. Because of their good work, I regularly support MedShare with my time and money.

I encourage you to support MedShare International through your contributions to 1% For The Planet. Thank you for considering requests from your customers. And thank you for all you do.

Sincerely,

Karama Neal

Letter to the Editor: Misuse of the Open Records Act

To the editor:

I am a strong supporter of the Open Records Act, and also advocate its judicious and responsible use. I was disappointed that the Atlanta Journal-Constitution chose to use the Open Records Act to read and report on e-mails sent from Claritha Nichols to her church member and spiritual leader who happened to be a Fulton County Sheriff's Deputy. (AJC, August 19, 2005, "E-mails display mom's agony", pg A1) Although the AJC acted legally, the resulting article unnecessarily invaded Mrs. Nichols privacy and grief, and did nothing to advance the public understanding of the Brian Nichols case. It was in poor taste.

Remember, just because you have the right to use the Open Records Act, doesn't mean you always should.

Karama C. Neal

Language and bias in Time

To the editor [of Time Magazine],

Although enjoyed your articles on President Abraham Lincoln and the times in which he lived and served (July 4, 2005), I was disappointed to find that your graphic identified the millions of Africans and African-Americans discussed as 'slaves,' a position they did not choose and one that violated their human rights. Please consider using terms like 'enslaved people' or simply, 'people' instead. These options restore and make obvious the humanity that these and all people exhibit. Recognizing and respecting this humanity is critical to ending the slavery and human trafficking that exisits today, even in the United States.

Karama C. Neal

State funding for MARTA

Dear Governor Perdue,

In January, after five years of working from home, I took a job that requires a 10 mile commute from my home. I was dreading the commute, until I realized that I could ride MARTA to work. That decision means that I now enjoy a comfortable, efficient, and productive commute. I am writing to ask that you support state funding for MARTA. It is vital for the citizens of metropolitan Atlanta and for the economic development of Georgia.

Many other cities with substantial transit systems receives significant portions of their operating budget from state funds (Boston - 54%, Philadelphia - 44%, New York - 29%, Chicago - 23%). Atlanta is a leading city in the Southeast, but in order to maintain and improve that position, we need to maintain and improve MARTA. Comprehensive and affordable public transit is vital to growing cities like Atlanta. It services not only the people who ride the MARTA, but also serves all the people of the region. Transit use reduces air pollution and traffic congestion, and provides transportation and a higher quality of life for the people of metropolitan Atlanta, whether or not they ride MARTA.

I agree that MARTA's budget, like that of all government agencies, should be balanced. However, metro-Atlatans and visitors to our region should not be forced to suffer higher fares and reduced services for that to happen. Unfortunately, that will likely be the result unless the State contributes to the MARTA budget.

Atlanta contributes greatly to the Georgia economy, and Atlanta needs the State to contribute to the Atlanta economy, through increased funding to MARTA. State support of MARTA is necessarly to adequately serve Atlanta and all of Georgia. Please consider providing it.


Sincerely,

Karama C. Neal, Ph.D.

Logistical support for the AU in Sudan

Dear President Bush,

Please make the genocide in Sudan a high priority for your administration. The United States can provide much needed help by providing logistical support for the African Union troops that have already committed to peacekeeping efforts. Please help end the suffering by providing non-combat logistical support for the African Union's work in Sudan.

Thank you,

Karama Neal

Kroger: plastic bag recycling

[Dear Kroger,]

Thank you for the excellent service and high quality products Kroger offers. It is no surprise that Kroger is the number one grocery store in the Atlanta area. Recently, I noticed that Kroger baggers began using only one bag for all but the heaviest items. Thank you! The extra bags contributed to waste, pollution and higher costs, so I hope this is a chain-wide change.

To further reduce waste and pollution, please place plastic bag recycling bins at your stores. This would be a valuable service to Kroger customers. Publix and WalMart (numbers two and three in Atlanta) have bins in their stores where customers can recycle grocery store bags. Please don't force Kroger shoppers to go to Publix to recycle our Kroger plastic bags.

Although I use cloth bags to carry some of my groceries, I still need a place to recycle excess Kroger bags. Please provide a place to do that at neighborhood Krogers.

Thank you for considering this idea.

[Karama C. Neal]

Darfur Accountability Act

Dear President Bush,

I am writing to request your strong support of the Darfur Accountability Act (S.495, H.R.1424). The actions mandated by this bill will stabilize the situation in the Darfur region of Sudan and in neighboring areas by reducing the number of deaths. It is critical that the United States act now, directly, and in support of the African Union, to stop the genocide.  Over 400,000 people have already lost their lives in this senseless tragedy. Millions of others have been displaced.

Georgia is home to many Sudanese refugees, commonly called "Lost Boys of Sudan." I have had several opportunities to talk with these men and women and those conversations have deepened my concern about the conflict in Sudan. Such instability is detrimental not only to the people of Sudan but to the world at large. As citizens of the world, we owe it to ourselves, and the people of Sudan, to stop this genocide.
 
Please support the Darfur Accountability Act and help make this possible.

Thank you very much.

Sincerely,

Karama C. Neal

Launch date

This blog will launch in early May. Please visit again then, and thank you for your interest.