Author, Lecturer, Ethicist

Filtering by Category: Medical Ethics

Throwing a Monkey Wrench into Medical Research

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This past week, while donning his horrendously-tailored “soup and fish,” dining with the Windsors and about-to-be former British P.M. Teresa May, commemorating the 75th anniversary of the D-Day Landing, playing golf in Ireland and bashing Senate Minority Leader Schumer, Speaker Pelosi and Director Mueller, ’45 somehow managed to find the time to throw a toxic monkey wrench into the future of medical research. ‘45’s announcement that the federal government is changing its policy on the use of human fetal tissue in medical research sent a collective chill up the spines of clinicians and researchers from Maine to California. His announcement - which has been percolating for quite some time - has precious little to do with science and everything to do with partisan politics. It is obviously designed to please the many anti-abortion groups which have strongly supported ‘45, the very man who once proclaimed on “Meet the PressI am firmly pro-choice in every sense of the term.”

As mentioned a few sentences above, the push for banning the use of human fetal tissue in government-sponsored research has been percolating for the past several years. The level of controversy around fetal tissue research waxes and wanes. Human fetal tissue research has been done in the United States since the 1930s, and NIH has been funding this type of research since the 1950s. There was a ban on such funding, however, during part of the terms of Presidents Ronald Reagan and George H.W. Bush. Federal money was restored with bipartisan support in a 1993 bill for the NIH. Among the backers of that effort were some strong abortion opponents, such as Sen. Strom Thurmond (R-S.C.), who argued that the research could help people — like his daughter — with diabetes.

NIH spent $115 million on human fetal tissue research in 2018, a tiny fraction of the nearly $14 billion it spent on clinical research overall. NIH currently funds roughly 200 projects that use fetal tissue, according to HHS.

Fetal tissue once again became a hot-button issue in 2015 with the release of doctored videos, later discredited, purporting to show Planned Parenthood officials discussing tissue donation policies and reimbursement. Last fall, the Trump administration announced it was conducting a review of all research involving fetal tissue to ensure it was consistent with statutes and regulations governing it.

Under the new policy, employees at the National Institutes of Health (NIH) will no longer conduct research with human fetal tissue obtained from elective abortions, after using up any material they have on hand. Officials also immediately stopped funding a multiyear contract at the University of California-San Francisco using human fetal tissue in mice to research HIV therapies. Federally funded projects at other research institutions using fetal tissue can continue until their grants expire. But renewal for these projects and future proposals will have to go through a newly established ethics review process to receive funding. It’s not clear yet what standards that process will entail or whether such experiments will be able to proceed under government sponsorship.

Additionally, under the new policy, extramural researchers who submit applications that pass scientific review and score high enough to be funded will now encounter a new and time-consuming layer of review. Under a procedure described in a 2006 law that governs NIH policy, HHS will need to announce in the Federal Register that it plans to assemble an ethics advisory board to review each proposed grant and invite public nominations for that board. The board would be made up of 14 to 20 people from various backgrounds, including at least one theologian, one ethicist, one physician, and one attorney. No more than half of the panel members can be scientists. The HHS secretary must wait at least 30 days after the publication to appoint the board. The board will then have up to 150 days to recommend to the secretary whether the proposed research should be funded.

Even then, the Secretary can overrule the committee if he finds its recommendation “arbitrary and capricious.” 

(Truth to tell, it has long been the case that every NIH-sponsored clinical trial must be thoroughly vetted and scrutinized by an Institutional Review Board [IRB] which is made up of physicians, scientists, bio-engineers, ethicists and so-called “public members.” I have been an active member of the largest of these boards for nearly 25 years and have easily vetted more than 2,000 research protocols in that period of time. So this is , in reality, nothing new.)

The anti-abortion (“pro-birth”) crowd has somehow convinced its followers that banning medical research which uses human fetal tissue will somehow keep women from obtaining abortions. Where they ever came up with this idea is beyond me. It has about as much logic behind it as enshrining the Volstead Act in our Constitution (about 100 years ago) , proclaiming that it would greatly reduce the number of people imbibing alcohol. What it did do was create a world of bootleggers, murderous gangs, bathtub gin and the likes of Al Capone, Frank Nitti and Eliot Ness.

Many of these same pro-birth advocates claim - in the name of scientific research - that there are “effective options” to using human fetal tissue, including monkey or hamster cells for vaccines as well as blood collected after birth from umbilical cords that are rich in blood-forming stem cells. They also suggest the use of adult stem cells and “organoids” — artificially grown cells that somewhat mimic organs. Another suggestion made to Alex Azar - the former president and chief lobbyist for Eli Lilly and Company and current Secretary of Health and Human Services - was that using tissue from a miscarriage could be an acceptable alternative to using tissue from an aborted fetus because it’s from “a natural death, not an intentional killing of the child.”

Checking with many of my IRB colleagues, they say that the use of adult stem cells and organoids “aren’t close to being ready for prime time. . . they cannot mimic real tissue.” The use of human fetal tissue in medical research holds out the hope for real progress coming up with therapies and even cures for HIV, Parkinson’s Disease, Diabetes and various forms of neurodegenerative disease such as Alzheimers Hunington’s and Lewy Body Dementia.

Considering the Trump family medical history, one would think that ‘45 would be more interested in doing research which might save his sanity - or that of his children and grandchildren in the future - than scoring electoral brownie points with anti-abortion activists in the present. The United States has long been a world leader in medical research. Creating new, potent and safe drugs, devices and procedures is a long and difficult process which requires scientific brilliance, firmly embedded in ethical practices. It also requires an absolute minimum of partisan politics. Diseases, syndromes and impairments are neither Republican nor Democrat, liberal or conservative. They can strike anyone and everyone.

We owe it to future generations to remember this simple truth and let the researchers get back to their labs and clinics and do what they do best.

516 days till the next election.

Copyright©2019 Kurt F. Stone

 

"The One Who Saves a Single Life . . . "

                              Drs.  Vibhav and Sonal Rangarajan and Their daughter, Radha

                              Drs.  Vibhav and Sonal Rangarajan and Their daughter, Radha

A couple of days ago, Attorney General Jeff Sessions stood before a gathering in Ft. Wayne, Indiana, and quoted the Christian Bible (Romans 13) as justification for the Administration's "Zero Tolerance" policy on illegal immigration. This is the policy which forcibly separates children from their parents if they cross the Southern border illegally.  According to Sessions, it is a lawful deterrent and is actually backed by the Bible.  “I would cite you to the Apostle Paul and his clear and wise command in Romans 13, to obey the laws of the government because God has ordained them for the purpose of order,” When asked to comment on Sessions' use of the Bible to justify the government's separating children from their parents, White House Press Secretary Sarah Huckabee Sanders doubled down saying it is "very biblical to enforce the law."  Of course, quoting standalone Biblical verses (from either the Hebrew or Christian version) to justify immoral actions on the part of the government is far from new: whenever Congress debates cuts in the food stamp program (SNAP - "Supplemental Nutritional Assistance Program") some damn fool will quote 2 Thessalonians 3:10: “The one who is unwilling to work shall not eat.”

As one who has spent the better part of a life studying (as opposed to "reading") both the Hebrew and Christian Bible in their original languages, I can, if called on, cite tons of verses from James, Matthew, Isaiah and Proverbs (to name but a few) which command us to "feed the hungry, clothe the naked visit the sick and take in and give shelter to the stranger."

This current crappola about citing Holy Writ to justify separating children from their parents brings to mind Antonio's admonition to Bassanio in Shakespeare's The Merchant of Venice (Act I, Scene 3, Page 5): 

Mark you this, Bassanio, the devil can cite Scripture for his purpose.
An evil soul producing holy witness Is like a villain with a smiling cheek,
A goodly apple rotten at the heart.

Having gone this far I must tell you that although I am about to quote an ancient religious text (not the Bible), this week's essay - although it does involve a child - has nothing to do with immigration and little to do with the federal government.  The passage comes from the 2nd century (C.E.) work Mishnah Sanhedrin 4:5

שֶׁכָּל הַמְאַבֵּד נֶפֶשׁ אַחַת מִיִּשְׂרָאֵל, מַעֲלֶה עָלָיו הַכָּתוּב כְּאִלּוּ אִבֵּד עוֹלָם מָלֵא. וְכָל הַמְקַיֵּם נֶפֶשׁ אַחַת מִיִּשְׂרָאֵל, מַעֲלֶה עָלָיו הַכָּתוּב כְּאִלּוּ קִיֵּם עוֹלָם מָלֵא   

Namely: "Anyone who destroys a life is considered by Scripture to have destroyed an entire world; and anyone who saves a life is as if he saved an entire world."

So what's this week's essay about?  Where am I going?  Well, yesterday, there appeared in my inbox an email from Vibhav Rangarajan, M.D., a practicing cardiologist/internist in Chicago.  Dr. Rangarajan graduated from Tufts University School of Medicine in 2010, and served his residency in Cardiology at the University of Illinois/Chicago. He is currently an instructor at the Feinberg School of Medicine at Northwestern, as well as being in private practice. He has been married since 2013 to Dr. Sonal Patel Rangarajan who specializes in pediatric gastroenterology.  They have a two-year old daughter named Radha, who was recently diagnosed with a "lysosomal storage disorder" . . . there are about 50 of these rare metabolic disorders.  The specific one that Radha has is called Metachromatic Leukodystrophy  (called by many names including "Greenfield Disease" and "MLD").  In his most heartfelt email, Dr. Vidhav admitted to having "memorized a few details about these rare diseases (lysosomal storage disorders) in preparation for my board exam, and then never gave them another thought." Why?  Because they are pediatric and he was going to be a cardiologist. Since Radha's diagnosis - which is bleak - he and Dr. Sonal have learned far, far more than they ever knew before.  

Without getting too technical, MLD is a genetic disease which interferes with the body's production of a single enzyme (protein).  Without enough of this particular enzyme - which ultimately insulates and protects nerves - all hell can break loose; it can destroy tissue throughout the brain, spinal cord, and other parts of the nervous system.  Quality of life - not to mention life expectancy - for a child with MLD is both bitter and brief.  As readers of The K.F. Stone Weekly know, I am not an M.D. - far, far from it.  However, I have been privileged to work with a team of world-class physicians, pharmocolgists, pathologists and diagnosticians for nearly a quarter century on an institutional review board, whose task it is to review, vet and make understandable, virtually every type of medical research protocol on the horizon. Our company holds a minimum of ten meetings a week via teleconference.  Over the years, I have attended hundreds and hundreds of these meetings and reviewed easily more than a thousand research protocols.  My main role is translating medical terminology into lay language. Sometimes, we review what are called "Compassionate Use Requests," which involve getting not-yet-FDA-approved and grossly expensive drugs to subjects who suffer from rare (sometimes called "Orphan") diseases and conditions.  We don't put the pressure on a particular company or drug manufacturer to grant the compassionate use status; rather, it is they who generally come to us, for it is our overarching task to insure the safety of the subject(s) who will be taking the drug.  

Regrettably, there are all sorts of diseases and conditions which do not have drugs, therapies or surgical procedures that are yet ready to be used.  It turns out, there is a drug being tested and developed for many lysosomal storage disorders, including Metachromatic Leukodystrophy by Shire Pharmaceuticals - a biotech firm which specializes in rare diseases.  At this point, Shire has even completed a multicenter Phase 1/2 trial of the drug (new drug trials generally go through phases 3 and even 4).  The drug is called SHP-611 (also known as HGT-1110) in Europe; it appears to be showing some promising results. But, for whatever reason, they have turned down the Rangarajan's request to grant Radha compassionate use status.  Why is anyone's guess, but it stinks to holy hell.  Her parents are doing everything in their power to draw attention to their daughter's plight; left untreated, this precious little girl could be in a vegetative state before too long, and likely won't ever see the age of 8. The FDA (Federal Drug Administration) cannot compel a company like Shire to provide Radha (even if her parents were able to pay) with SHP-611/HGT-1110. Recently, the president signed into law a controversial piece of legislation called the "Right to Try" law which, at least in theory, would offer terminally ill patients expanded access to unapproved treatments.  Despite crowing about how many lives will be saved by means of this legislation ("We will be saving — I don’t even want to say thousands because I think it’s going to be much more — thousands and thousands, hundreds of thousands, we’re going to be saving tremendous numbers of lives. There were no options, and now you have hope.”) the bill's true purpose is to undermine the FDA by eliminating many of the regulations they impose and oversee - regulations which ultimately protect test subjects and ultimately, patients.  Why?  Perhaps because eliminating regulations will make bringing new drugs, devices or procedures to market will be a whole lot less expensive.

When I read Dr. Vibhav's email, I was touched to the core.  Knowing that many of you - my beloved readers - are people of quality and compassion - I have decided to issue a plea . . . that you and your friends sign a petition to Shire, urging them in the strongest possible terms to grant compassionate status to Radha.  As of a few minutes ago (8:35 PM (EST) June 17, 2018 - nearly 180,000 people have signed the Rangarajan's petition to Shire.  I urge you to add your name (and perhaps a couple of dollars) to the cause. 

Do remember that ancient truth expressed in the Mishnah: "Anyone who saves a single life, it is as if that person had saved the entire world."  In his time of gross insensitivity, where each day brings hideousheadlines about man's inhumanity to manwhere every day brings yet another hideous headline; so many of us are frustrated, freaked out and feeling oh so powerless against the forces of narcissistic self-centeredness.  Well, I'm here to tell you that we do have power; we actually can make a difference, if only we find our communal voice and make our humaneness known. I urge you and your friends to  speak up on behalf of Radha; put her plight on your Facebook page; send Dr. Rangarajan's email to everyone on your list. Save Radha's life . . . save the universe.

From what I've recently learned, in Sanskrit, "Radha" (राधा) means 'success' or 'prosperity.' Together we can, G-d willing, give her the chance to live up to her name and succeed at life, while prospering in terms of health. Then too, by doing what we can for her and her family, we too can succeed and prosper.

Find you voice!

516 days down, 957 days to go.

Copyright©2018 Kurt F. Stone

 

 

The Right to Try: Is It a Lie?

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Last Tuesday (March 13, 2018) in a gutsy, contentious vote, the Republican-controlled House failed to pass a "right-to-try" bill (H.R. 5247) that would have given terminally ill patients access to experimental drugs and medical devices without FDA authorization. The final 259-140 vote, which fell short of the necessary two-thirds support from the House chamber, represented a setback for the president, who called on Congress to approve the bill in his State of the Union address six weeks ago . . . as well as a small libertarian think tank (the Goldwater Institute)  which has been the driving force behind the effort.  The bill - which got to the House floor without having gone through a single committee hearing - would permit patients suffering from terminal illnesses, upon a request from their physician to a specific pharmaceutical company or medical device manufacturer, to get access to a non-approved medication or device available without having to go to or through the FDA.  While at first glance the legislation would appear to be a compassionate no-brainer, this "right-to-try" legislation (RTT) is, in reality, a lie whose main beneficiaries are not terminally-ill men, women and children.

In his first State of the Union address, the only piece of legislation 45 specifically mentioned was this "right-to-try" bill, which had, in a slightly different form, unanimously passed the Senate.  In the president's address, he said: "We also believe that patients with terminal conditions should have access to experimental treatments that could potentially save their lives. People who are terminally ill should not have to go from country to country to seek a cure — I want to give them a chance right here at home. It is time for the Congress to give these wonderful Americans the 'right to try.'"  On the surface, right-to-try legislation seems like a no-brainer;  after all, who but a heartless ghoul would deny terminally ill patients access to potentially life-saving drugs, treatments or devices?  That's on the surface. However, descend a few steps beneath that surface and a plethora of problems begin to emerge.  

First and foremost is the matter of safety.  The  proposed federal law would only require the successful completion of a Phase I study, which isn’t enough to ensure efficacy or safety on its own. (Phase I studies, which enlist healthy subjects, are primarily interested in determining what - if any - adverse events [bad side effects] a drug may have; what the maximum tolerated dose [MTD] might be, and how the body absorbs, metabolizes and excretes the drug [PK].  What a phase I study does not look for is whether or not the drug, device or procedure is beneficial - i.e. capable of having a curative effect. In order to find out if a drug or device works requires additional phases using subjects who actually have the disease or malady.  The "gold standard" for a phase II or III study is called "Double-blind, placebo-controlled," in which neither the doctor nor the subject knows whether they are receiving the study drug or a dummy "sugar pill." All these phases (which can also include phase IV and post-marketing) take years and tens - sometimes hundreds - of millions of dollars to complete. But underlying all the research is the ethical mandate "First, do no harm."  Contrary to our unfounded optimism about medical progress which insists that new drugs must be good drugs, fewer than 10 percent of drugs that enter Phase I end up being approved; for oncology, that figure falls to 5.1 percent.  In other words, "right-to-try" drugs, far from having passed scientific or medical muster, can be unproved and worthless at best, lethal at worst. 

In clinical trials, participants (and/or their insurance carrier) are only charged for "standard-of-care" procedures.  The sponsor pays for everything else . . . especially the medication.  Under terms of the "informed consent" (which all test subjects read and sign before entering a test phase), if the medicine(s) or procedures cause any harm, the sponsor is financially responsible and the participant does not lose any of their legal rights.  Under terms of federal right-to-try legislation, the patient (or their insurance carrier) is on the hook for payment - which can be in the hundreds of thousands of dollars - and cannot sue.  Then too, the very act of using right-to-try therapies can render terminally-ill patients ineligible for health insurance or hospice care when they need it most. Of the right-to-try laws (now on the books in 38 states), half allow insurers to deny patients hospice coverage should they require it after the use of right-to-try drugs. Several have made it clear that health insurers are not obligated to cover the costs of any complications that may arise.  In Colorado, patients undergoing experimental treatment secured under terms of right-try legislation are denied coverage even six months after the treatment has ended.

Unbeknownst to many, the Food and Drug Administration (FDA) has long had an "Expanded Access Program," under terms of which a terminally ill patient’s treating physician, after first having determined that their patient ". . . has a serious or life-threatening condition and no comparable or satisfactory alternative therapy" . . .  then approaches the pharmaceutical company to ask for its agreement that it will provide the drug being sought.  The company has the right to approve or disapprove the physician’s request."  If the company agrees to the physician’s request, the physician can then apply to the FDA for permission to proceed.  Should they do so, they are highly likely to be allowed to proceed. (Between 2010 and 2015, the FDA approved fully 99% of these requests.)  Opponents of this process (starting with the Goldwater Institute) claim that a terminally ill patient could be dead long before the paperwork has been completed.  This is simply not true. Today, the FDA Expanded Access form takes 45 minutes to complete, and the FDA will reply to emergency requests within no more than 24 hours.

So once again, on the surface, federal "right-to-try" legislation seems to be as simple, logical and compassionate as anything under the sun. To libertarians, it is simply a matter of the government keeping the hell away from the individual's right to choose for themselves (except, of course, if that individual is a pregnant female). Who but a political Simon Legree could deny dying patients the right to try unproven medications . . .  even if it turns out to be a "hail Mary pass?"

Who indeed?  Days before the failing House vote (in which 2 Republicans crossed over and voted nay, and 24 Democrats yay), more than 75 patient groups, including the American Cancer Society Cancer Action Network, the American Lung Association and the Cystic Fibrosis Association, had sent a letter to House leaders saying the bill “would not increase access to promising therapies” because it didn't deal with the main barriers to experimental drugs  — the cost of drugs and company restrictions on making therapies available outside of clinical trials.  And by skirting the FDA, the letter added, the proposed right-to-try pathway would be “less safe” for patients than the agency's existing program (expanded access), for overseeing the use of unapproved therapies outside of trials.  Reading between the lines, the goal of federal "right-to-try" legislation is not to make experimental drugs available to desperate patients. The goal is to weaken FDA oversight of the drug approval process.  Weakening FDA oversight can easily open the gates, admitting a parade of medical charlatans to come storming through, preying on the already desperate, dangling "miracle cures" which may well contain nothing more miraculous than hot air and hollow promises.

423 days down, 1,036 days to go . . .

Copyright©2018 Kurt F. Stone