GOV'T FINDS #INDIA STUDY UNETHICAL #ASCO13 PROTECT #WOMEN

WHY is he being hailed as a "health hero" by the media who picked up the story?  WHY aren't the ethical concerns even mentioned in any of the stories that have touted this vinegar fix for cervical cancer screenings as huge news?

((Might be hard to follow this unless you start with yesterday's post..... which includes the links to my post in February when I first learned of the problem with this research.  I followed it up in March with another post questioning the whole mess))

Make NO MISTAKE.  The result is huge and it's spectacular.  It holds promise to save many lives each year.  None of that is being questioned.

This is the question:

Does the end justify the means?

In my mind, absolutely not.

I was beginning to feel like a pariah.  How is it that NO ONE is talking about the other side of this story?

I know.  I'm a blogger.  I'm not a writer.  This isn't journalism.  According to the line in the movie Contagion, blogging isn't writing.  What I do?  According to the screenwriters, "It's graffiti with punctuation."  And sometimes, the punctuation isn't even valid.  I write like I speak.  Sometimes phrases are sentences.

But I am always truthful.  I call it like I see it.  I may lose popularity points but I can put my head on the pillow at night.  I can look into a mirror and respect the integrity of the image in the mirror.

I wrote about the study in February.  I saw a tweet from a doctor I consider to be quite prominent alerting me to the fact that there was going to be a discussion at the ASCO meeting about cervical cancer in India.  I jumped into high gear.  I left a comment on the Forbes blog expressing my concern over the ethics of the study.

I was told by the author of the article he thought the study was completely ethical.  I wrote a lengthy response to the "completely ethical" remark.  It went like this:

Respectfully disagree. The endpoint is death when we are looking for effective treatments where none exists. In this case, we know there is curative treatment. Study could have been designed differently. Illiterate women **showed up** which seems to indicate they knew they would be helped. Being sent home after being told about the availability of PAP test with copies of written informed consent forms to look at (which was indeed **missing** the information about PAP testing despite its inclusion in the grant application) muddies the waters. Did the women understand what they were being told? I have participated in studies and the written consents that I have come home with are lengthy documents. Does one really grasp all of the information being explained while in a medical setting? Would it have been helpful to have the complete info in the forms they were sent home with so someone else might have been able to explain fully to this largely illiterate group of controls? I’m sorry.. there are far too many things in this design that are not ethical. We know that vinegar is an effective tool. It is still used in this country to identify areas that may be suspicious following a questionable PAP test. There was no difference in the number of cancers in each arm is expected information. It would be expected that being screened would detect cancer earlier. That’s the whole purpose of screening, isn’t it? Sending women home without screening because that’s the “standard of care” in a third world country is not an acceptable explanation to me. Lives lost due to shoddy study design is disgraceful. These women were used as lab rats. I’d love to someone interview the controls to see what they truly understood. Were they truly informed participants? When a Harvard ethics professor makes a statement, “When you recruit research subjects, you take on a responsibility that can’t be ignored, you have to do the best you can for your controls,” I step back and ask the question. Did we do the best we could for the controls? The answer. Absolutely not. They were allowed to die. Why the scramble in both studies (Gates study, too) to screen all of the controls only after the complaints were lodged by Dr. Eric Suba? I am NOT a **conspiracy theorist” …. I’m just a volunteer advocate who understands a bit about research and study design based on my own experience as a breast cancer patient and as part of my volunteer advocacy. A design using comparative effective research, although not the RCT gold standard, might have been a better option. I stand by my beliefs. Death is the endpoint when we are seeking treatment for which there are no other options. That was simply not the case in this situation.

Yesterday, I was distracted for much of the day and it wasn't until much later that I saw this comment, also in response to the "completely ethical" remark:

The U.S. Office for Human Research Protections has determined that this study is unethical. You may wish to reconsider your support for this study in light of that determination, available at: http://www.hhs.gov/ohrp/detrm_letrs/YR12/jul12d.pdf

Followed by this, from the same person..... that person being Dr. Eric Suba.  The Whistle Blower.  Bold emphasis is MINE....

It is scientifically implausible that unscreened control groups and mortality endpoints would be needed for cervical screening studies in India, but nowhere else. U.S.-funded studies of cervical screening in India provide further examples why India is considered one of the worst places on Earth to be a woman.

Cervical screening and smoking cessation both received ‘‘A’’ recommendations from the U.S. Preventive Services Task Force in the absence of randomized trials confirming effectiveness. No one unaffiliated with the tobacco industry has suggested delaying large-scale lung cancer prevention efforts pending completion of randomized trials comparing smoking to no-smoking. It is tragic that U.S.-funded leaders have advocated delays in large-scale cervical screening efforts in India pending completion of scientifically gratuitous, ethically problematic randomized trials comparing cervical screening to no-screening. India reports more cases of cervical cancer-related death than any other country on Earth.

A principal objection to the scientific design of U.S.-funded cervical screening studies in India has been that experimental measurements of cervical cancer death rates among women not offered cervical screening would not change clinical practice. If cervical screening (compared to no-screening) showed significant correlations with cervical cancer death-rate reductions, the experimental result would be considered gratuitous; and if cervical screening (compared to no-screening) failed to show significant correlations with cervical cancer death-rate reductions, the experimental result would be considered absurd and would not be generalized to any other setting.

The Mumbai study has been determined to be unethical by the U.S. Office for Human Research Protections for the same reason the 20th-Century Tuskegee syphilis study had been determined unethical: participants were not given facts required to provide informed consent. Providing basic facts about cervical cancer prevention to women at high risk for death from the disease rapidly creates powerful demand for screening services. Creating and maintaining large groups of unscreened women required incomplete informed consent. If the 138,624 women in the unscreened control groups of U.S.-funded India studies had been given basic facts about cervical cancer prevention, many if not all of them would have sought screening on their own, thereby ruining the scientifically problematic study design.

Remarkably, the President of ASCO has dismissed OHRP’s determination, stating categorically that “There was no wrongdoing there.” It is unclear whether she was speaking on behalf of the Society.

Have a listen...... The letter from the Office for Human Research Protection (OHRP), copied below in its entirety, can be found here.

The man being hailed as a "Health Hero" is the Principal Investigator noted in this correspondence.  And the author of the Forbes piece may want to rethink his stance about the "completely ethical" nature of the study.  The OHRP made an initial inquiry.  They received a reply from the hospital which did NOT satisfy the OHRP.

Again, emphasis in the letter is mine and in light of saving the eyesight of those who do not wish to read the entire letter, the key points from the OHRP...... coincidentally, they are precisely the issues I raised for several months.  (FYI, I didn't see this letter until very late yesterday, after I already opened my mouth a number of times.  Smugly and quite sadly, the OHRP confirmed many of my questions) 

• Women were NOT adequately informed.
• Verbal information may not be recalled which is why written forms are essential.
• The written "sample" provided in the grant application was not included in the translated copies provided to the women.

My MOM sent me an email referencing a story in Newsday.  She wrote:

"Seems to me they make it sound promising, unless I missed something.  I am going to read it again."

No mom, you didn't miss a damn thing.  NO ONE is telling this side of the story.  NO ONE is standing up on behalf of the women in India.  Except Eric Suba, the REAL hero in all of this ..... and Bob Ortega for writing a stellar piece of journalism.

My biggest problems....

HOW was this dismissed by the president of ASCO?

WHY is this doctor, the PI, being hailed as a hero?

WHO is telling the story aside from Bob Ortega?

WHERE is the outrage?

And the biggest problem of all?

WHAT the hell is going on and again, WHERE is the outrage????

Shame on everyone who had anything to do with this and shame on the "real journalists" for not standing up.  Shame on ASCO for allowing this man to share his ill gotten findings at a prestigious meeting on a world stage.

Again, I fully acknowledge the research is quite valuable.  It will save lives.

It wasn't necessary to sacrifice OTHER lives in the process.

That is the disgrace in this whole sordid mess.

HERO?  I think not.  What is described in this letter is many things.  Heroic is definitely NOT one of them.....

Is anyone listening?  Can you hear me now??  Will you give this story the coverage it deserves???  Who???  When????  I'm waiting........

Here's the info you need.  Straight from the US Government Department of Health and Human Services........ If any one of the parties to whom this letter was addressed wishes to provide a response in defense of these actions, I will gladly print it here.  Ditto, ASCO.

Office for Human Research Protections
The Tower Building
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Telephone: 240-453-8132 FAX: 240-453-6909
E-mail: Kristina.Borror@hhs.gov

July 5, 2012

Dr. Anil K. D'cruz, M.S. Director
Tata Memorial Hospital
Dr. E. Borges Road
Parel

Mumbai, Maharashtra
INDIA

RE: Human Research Protections Under Federalwide Assurance FWA-6143
Research Project: Early Detection of Common Cancers in Women in India
Principal Investigator: Dr. Surendra Srinivas Shastri
HHS Protocol Number: 5R01CA074801

Dear Dr. D'cruz:
Thank you for your June 4, 2012 report in response to our May 7, 2012 request that Tata Memorial Hospital (TMH) evaluate allegations of noncompliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46). Based on review of your response, we make the following determinations:

A. Determinations regarding the above-referenced research

(1) We have determined that subjects were not adequately informed of the alternative procedures or courses of treatment regarding screening for breast cancer or cervical cancer, namely, mammography and Pap testing. HHS regulations at 45 CFR 46.116(a)(4) require the disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject, as part of informed consent. The research study involved offering the subjects a form of screening for breast and cervical cancer that is different from mammography and Pap testing which are considered the “gold standard” for such screening. It has been reported that the medical social worker responsible for obtaining the consent from subjects gave an unbiased verbal listing of nearby screening facilities providing Pap smears and mammography, which may be free or may require payment.

However, based on our review of the materials used to brief the prospective subjects about the research study, we believe that subjects were not provided with adequate information to understand the differences between the research procedures and mammography and Pap smears. Understanding what their alternatives are is key to the subjects’ ability to make an informed decision about whether or not to participate in a research study. While an institutional review board (IRB) reviewing this study would have the authority, under appropriate circumstances, to have modified or waived this regulatory requirement, we do not find any evidence that the IRB modified or waived this requirement for the above-referenced research.

(2) We have determined that the subjects were not provided, in writing, with information about the possible alternative of seeking breast or cervical cancer screening outside of the research. Obtaining informed consent is required by the HHS regulations at 45 CFR 46.111(a)(4). Disclosing appropriate alternative procedures or courses of treatment as part of informed consent is required by the HHS regulations at 45 CFR 46.116(a)(4). Using a written consent document that embodies the elements of informed consent identified in 45 CFR 46.116 is required by HHS regulations at 45 CFR 46.117(b)(1). We note that the HHS regulations at 45 CFR 46.116 allow the IRB to approve a waiver or alteration of informed consent under certain conditions, and that the regulations at 45 CFR 46.117 allow the IRB to approve the use of a short form or a waiver of documentation of informed consent (e.g., to allow the information to be provided to subjects verbally, but not in written form, and as noted above, there is a claim that the subjects were indeed given this information verbally), but there is no evidence that the IRB chose to utilize these options.

We note that the 2010 grant application indicates that subjects were “made aware of the availability of breast and cervical cancer screening methods like mammography and Pap smear” and the model informed consent document from the 2005 grant application stated “The standard screening procedures for cervix and breast cancers are Pap smear and Mammography, in developed countries. Such facilities are also available in some centres in India and you may choose to undergo these tests on your own, if you do not wish to participate in this study.” However, a translated copy of the informed consent document actually used in the study that we were provided did not include this language. When such information is only provided verbally, subjects may not recall the information later, or may not fully understand what is told to them orally. Therefore the default is that such information must be provided in writing, unless the IRB finds legitimate reasons to waive the regulatory requirement that informed consent be documented in order to allow the information to be provided verbally.

(3)  We have determined that the IRB failed to conduct continuing review of research at least once per year. The HHS regulations at 45 CFR 46.109(e) require that continuing review of research be conducted by the IRB at intervals appropriate to the degree of risk, but not less than once per year. We note that the study received HHS support from 1997-2003 and 2005 to the present; however continuing review did not occur during the following years: 2000, 2003, 2006, and 2008. Continuing review by the IRB is important, in part, to determine whether there is any new information provided by the investigator, or otherwise available to the IRB, that would alter the IRB’s previous conclusion that (1) the risks to subjects are minimized, and (2) the risks to subjects are reasonable in relation to anticipated benefits, and that the safeguards in place at the time of original approval are, in fact, adequate to ensure the safety of subjects.

(4)  We have determined that minutes of IRB meetings do not exist (or were not provided to our office upon request) for the following meetings: September 25, 1998; June 22, 1999; November 17, 1999; August 17, 2001; June 17, 2002; February 24, 2004; and that minutes of IRB meetings that were provided to us are not in sufficient detail to show the vote on actions taken by the IRB including the number of members voting for, against, and abstaining. The HHS regulations at 45 CFR 46.115(a)(2) require that meeting minutes including this information be written and maintained. It is important to maintain documentation of IRB actions and discussions so that the institution has a record of what transpired at the meetings, what decisions were made and actions taken. This is also important for future decision-making about a particular project.

(5)  We have determined that the IRB failed to meet the quorum requirement for the IRB meeting of April 11, 2007. The HHS regulations at 45 CFR 46.108(b) require that research be reviewed at convened meetings at which a majority of the members of the IRB are present, except when an expedited review procedure is used. We note that our records indicate that the IRB had 16 members during this time, but only 3 members were present at this meeting.

Required Action:
Please provide us with responses to the above determinations by August 10, 2012, including a corrective action plan for each of our determinations. Feel free to contact me if you would like guidance in developing a corrective action plan.

We appreciate the continued commitment of your institution to the protection of human research subjects. Please do not hesitate to contact me should you have any questions.


Sincerely,
Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight

cc:
Dr. Rajendra A. Badwe, Director, Tata Memorial Centre
Dr. Madhuri Gore, Chairperson, Human Ethics Committee-I, Tata Memorial Hospital
Dr. Urmila Thatte, Chairperson, Human Ethics Committee-II, Tata Memorial Hospital
Dr. Surendra Srinivas Shastri, Tata Memorial Hospital
Dr. Margaret Hamburg, Commissioner, Food and Drug Administration (FDA)
Dr. Joanne Less, FDA
Dr. Sherry Mills, National Institutes of Health (NIH)
Mr. Joseph Ellis, NIH

Dr. Harold Varmus, Director, National Cancer Institute, NIH