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As Genetic Testing for Breast Cancer Gene Mutation Expands, Questions Arise About Treatment Decisions

Posted on May 18, 2018

This post originally appeared on The Conversation on May 3, 2018.

 

The Food and Drug Administration recently announced its authorization that permits genetics testing company 23andMe to market a test for gene mutations associated with risk of breast and ovarian cancer.

In response, 23andMe CEO Anne Wojcicki asserted that the test represents a “major milestone in consumer health empowerment.”

Media articles following this announcement made it clear even if the test provides an accurate result, there are significant limitations for 23andMe’s version of the test about which consumers should be aware. Notably, 23andMe discloses that the test only provides information on three genetic variants found on the BRCA1 and BRCA2 genes known to be associated with a higher risk for breast, ovarian and prostate cancer in people of Ashkenazi Jewish descent.

According to the FDA, most mutations that would increase an individual’s risk are not detected by the test, including mutations that may occur in other patient populations.

As a health law professor and bioethicist, here are some things I think that patients should know about genetic tests and how to think about risk.

A bit about assessing risk

Research shows that women overestimate their risk of cancer and overestimate the potential of dying of cancer. This anxiety may prompt women to seek aggressive interventions even when they do not have cancer. In one study, 32.9 percent of women without a BRCA mutation who received a false positive (indicated they had cancer when in fact they did not) on a screening test for ovarian cancer and had no ovarian cancer opted for surgical removal of their ovaries, or an oophorectomy.

It is imperative to address this anxiety and situate what a cancer risk means for patients.

For starters, it is important to know that the chance of having a BRCA mutation is exceedingly rare, with only about 0.2 percent of population affected. Put another way, in a room of 500 women, only 1 would have a BRCA mutation that increases her baseline risk of breast and ovarian cancer. But even this woman with a BRCA mutation may never develop breast or ovarian cancer during her lifetime. In fact, 90 to 95 percent of most cancer diagnoses can be attributed to environmental and lifestyle factors, not an inherited faulty gene.

According to the Fred Hutchinson Cancer Research Center, up to one-third of cancer-related deaths are due to obesity and sedentary lifestyle. “Exercise is one of the most important actions you can take to help guard against many types of cancer,” experts at Fred Hutchinson say. A trial published in JAMA Internal Medicine confirmed the strength of dietary modification to drastically reduce risk of breast cancer. This information should be empowering. Many patients have much more control over certain – but not all – risks than they may have thought.

These discussions raise broader questions about how we treat patients regardless of whether they have an increased risk of cancer based on genetic testing or fall into a high risk category based on family history. For patients to make meaningful health decisions, they must have accurate information that includes understanding the risks and benefits of each choice.

Implications for overtreatment

Overtreatment that stems from anxiety not only leads to unnecessary and potentially harmful interventions for the patient, but it implicates physician liability. Traditionally, oncologists may favor an aggressive approach, offering and recommending interventions as a means to avoid malpractice litigation arising from patient perception that a physician could have intervened sooner. Aggressive treatment prompted by a patient’s anxiety requires further scrutiny specifically because each preventive intervention entails serious risks.

To note, 23andMe does caution that its test results should not be used on their own to make medical decisions. Women who test either positive or negative should still follow up with their physicians, both 23andMe and the FDA say.

If a woman has a BRCA mutation that increases her risk of cancer, the physician would likely recommend a risk-reducing measurerecommended by the National Cancer Institute: chemopreventionpreventive mastectomy with reconstruction, and surgical removal of ovaries and fallopian tubes, called salpingo-oophorectomy.

In the majority of cases, women who undergo mastectomy also opt for implant reconstruction, and women who undergo salpingo-oophorectomy begin taking synthetic hormone replacement therapy.

In my research, I’ve read countless clinical practice guidelines, FDA meeting minutes, congressional hearing transcripts, and case law.

Here’s what I’ve learned: The potential for cancer risk reduction is only the first part of the equation. Yes, these interventions recommended by the National Cancer Institute do reduce risk for breast and ovarian cancer. But they also increase risk of other potentially debilitating or deadly conditions.

Many physicians agree the trade-off of reducing risk of cancer is worth it. But some physicians and patients may not be aware that physicians and clinical practice guidelines may downplay, omit or dismiss risks entirely in a manner that does not necessarily correspond to scientific evidence, but may be informed by financial conflicts of interest.

Health empowerment requires a much broader conversation of what patients – both with and without a BRCA mutation – can do about their risk of cancer. On a population level, I believe everyone should have information on how to reduce cancer risk through diet and lifestyle interventions. Let’s continue the conversation of how to address patient anxiety to prevent needless overtreatment, aim for communication that accurately portrays what risks mean, and determine whether recommended interventions that pose significant risks offer sufficient clinical benefits.

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Hawaii’s New End-of-Life Law: Do the Additional Safeguards Withstand Scrutiny?

Posted on May 18, 2018

This post originally appeared on The Hastings Center Bioethics Forum on May 4, 2018.

 

Last month, Hawaii became the seventh state, with the District of Columbia, to legalize physician-assisted suicide. Similar to some of the other state laws, Hawaii’s Our Care, Our Choice Act permits competent adults with a terminal illness and a diagnosis of less than six months to live to obtain a lethal prescription to use to take their own lives. Proponents assert the new law, in addition to giving patients a measure of control, autonomy, and dignity, also contains rigorous safeguards. Despite this rhetoric, Hawaii’s law, like legalized PAS in general, raises troubling implications for the standard of care and for transparency. It also highlights the immense power of a lobby, Compassion & Choices, to strategically politicize language and control the public discourse to make legal change appear to result from organic social shifts rather than orchestrated actions.

Terminology matters: framing a lethal prescription as a viable and even desirable alternative to addressing shortcomings in palliative and hospice care obfuscates that “care” and “choice” mean supplying vulnerable patients with a medication to end their life. Under the prevailing medical standard of care, patients who report feeling depressed, a burden to others, trapped, or hopeless, or are struggling with managing their medical condition would ordinarily trigger intervention to address risk factors for suicide. However, lobbyists’ use of euphemistic language may incrementally change how physicians and public health professionals respond to patients who express suicidal thoughts.

Understanding the patient’s psychological condition is important because research in Oregon has found that patients considering PAS have concerns relating to loss of autonomy, ability to engage in activities that make life enjoyable, and loss of dignity. (Contrary to popular belief, excruciating pain is not a substantial factor in patient decisions to seek PAS.)  Under Hawaii’s law, however, a patient may obtain a consultation via telehealth. While telehealth promises to reduce cost and increase efficiency to address other health care issues, we should pause to consider the sufficiency and ethics of a remote consultation with patients to discuss their motivations and screen for potential problems.

I take issue with what I see as a pro forma requirement. It looks like a protection, but it’s not designed to address underlying issues such as a patient’s depression and whether it could be relieved. Patients facing psychological, social, or existential concerns deserve compassion in the form of reassurance, social support, and practical solutions to address feeling like a burden on others. Needing connection and validation throughout our life–and especially at our most vulnerable when we require assistance from others–translates to knowing that we are meaningful and loved.

Dr. Herbert Hendin and Dr. Kathleen Foley perhaps framed it best: patients desperately need relief from mental and physical distress, and without such relief, they would rather die. Relieving patients’ distress requires enabling and supporting a medical system and standard of care that permits physicians the time and reimbursement to address patient desperation and ambivalence and to offer solutions and referrals to competent providers.

Because of the construction of Hawaii’s law, we are unlikely to know how physicians counsel patients on alternatives and screen patients’ decision-making ability. As in Oregon, the Hawaii State Department of Health will collect limited records, which are confidential and not legally discoverable. While this protects patient privacy, the lack of transparency undermines any claims refuting abuse: we simply cannot know the content of these conversations. We do have access to a select few private medical conversations published in the media, which prompted critics to assert that limited recordkeeping enables patients to go physician-shopping and have brief pro forma discussions.

As a society, we should be skeptical of a practice that arose from lobbying and relies on politicized language to fundamentally alter the physician’s traditional role and the standard of care. I posit Hawaii’s “rigorous safeguards” constitute hollow promises.

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Engineering Consensus in the Development of Genome Editing Policy

Posted on Mar 14, 2017

This commentary was originally published as an Essay on the Hastings Center Bioethics Forum here.

 

In the past few weeks media outlets have been reporting on the release of Human Genome Editing: Science, Ethics, and Governance from the National Academies of Science, Engineering, and Medicine. The report concluded that following more research, it would be ethical to initiate clinical trials using heritable, germline genome editing for therapeutic purposes subject to a set of conditions. Described by some as a “fantastic development,” this declaration effectively lifted the nonbinding temporary moratorium from the International Summit on Human Gene Editing in 2015.

Although the lengthy report suggests extensive deliberation, it glosses over troubling scientific evidence pertaining to risks of gene editing and stands in stark contrast to the current widely held view in many countries against human germline modifications.

Scientists have referred to potential human germline modifications using gene editing tools as elegant, accurate, and precise, which connotes an exact application to correct a deficiency. This focus marginalizes the complexity of intervening environmental and other epigenetic factors, and presumes that editing technology constitutes the rational, and only, solution toward progress.

After all, who would want to cause “unnecessary misery” and prevent medical advancement?  Placing the ethos of suffering and survival at the forefront of the debate appeals to the very core of what we want from medicine and technology: better health, more certainty in prognosticating outcomes, and the deep primal yearning to have “healthy” genetically related children. The problem arises when the genomic model becomes the sacrosanct idol, and opposing it is attributed to misinformation and unsubstantiated fears.

In the past few years, scientists and bioethicists have discussed the serious potential risks involved with gene editing, such as mosaicism, off-target effects, and incomplete editing.  Last July, Stat News highlighted growing evidence that there may be more off-target effects that originally predicted. Discussion of potential errors presumes that scientists have sufficient information to target the correct part of the genome to “fix.”  However, biologist Stuart Newman  has suggested that this preliminary assumption may not be correct, because variants classified as pathogenic may not be harmful in all individuals.

These limitations reinforce what many scientists and scholars have observed: that germline modifications will always carry a margin of risk. The question then becomes, who the policy discussions accurately characterize the weight of the scientific evidence and explore nuances contained in that model of risk?  Recently, the United States approached a similar quandary, whether to permit germline modification via mitochondrial replacement therapy. Unlike some who have praised this model as a pathway to inform gene editing, I see troubling parallels between the policy evolution of mitochondrial replacement therapy and gene editing, which should give us pause.

Back in 2014, scientists convened before the FDA to discuss mitochondrial replacement therapy, describing the inability to predict safety and assess latent risks and listing potentially insurmountable hurdles arising from intricacies of mitochondrial biology. Numerous statements from participants cautioned against the lack of evidence pertaining to safety and efficacy, the potential to cause abnormalities, and the gravity of risk involved.  Despite these warnings based on scientific considerations, the National Academies of Science, Engineering, and Medicine recently concluded that conducting clinical trials for mitochondrial replacement therapy is ethically permissible. Although the process for both mitochondrial replacement therapy and gene editing provides the appearance of deliberation, it reveals a disconnect between the state of the science and the characterization of the science while obscuring likely motivational drivers: the pursuit of scientific prestige and capturing a highly lucrative commercial market.

Presuming the inevitability of gene editing in the U.S. also fails to situate our nation within the international context.  Many countries, including Canada, Germany, France, Switzerland, Sweden, and Italy, have adopted legislation prohibiting germline intervention on human embryos for implantation. In some of these nations, germline modification constitutes criminal violation subject to fines and or imprisonment. Prohibiting and criminalizing an action communicates its egregiousness, potential for harm, and social unacceptability in these nations  Unlike the alarmist rhetoric that the U.S. is falling behind and failing to invest in promising genomic technologies, these laws demonstrate the opposite: many countries acknowledge the lure of technology, but renounce risky experiments that cross the historical bright line of manipulating future generations.

As UNESCO’s International Bioethics Committee  has cautioned, neither professional accolades nor market forces should drive the adoption of genomic technologies.  It is crucial to not only step back to assess chasm between the very significant risks pertaining to germline modification and the National Academies current stance, but also to ask why the policy deliberations have been so swift to affirmatively declare that the benefits would outweigh these risks in future clinical applications.

 

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Questions about Deaths in Cancer Trials using Gene-Altered Cells

Posted on Jan 9, 2017

This article was originally posted on The Center for Genetics and Society’s site here.

In the past month, the media has reported seven patient deaths of subjects enrolled in separate gene therapy clinical trials being conducted by Juno Therapeutics and by Ziopharm Oncology, Inc., both aimed at immunotherapy-based cancer treatments that have sparked widespread hope. Despite these deaths, the trials continue to move forward.

Media coverage of trials related to gene therapy has portrayed the clinical research rollercoaster.  Just this past week, The New York Times ran an unusually lengthy and high-profile series of articles in the Sunday paper about immunotherapy treatments for cancer, some involving genetic modification of immune cells. The articles describe the promising aspects of engineering one’s own immune system to fight cancer, including dramatic stories of tumors “melting away” and promises of complete remission.

Yet commentary on the ethical implications of these events has been scant, and these events raise a number of concerns about what bioethicists call “therapeutic misconception” – vulnerable patients seeking enrollment in a clinical trial with the mistaken belief that the gene therapy is approved by the FDA to be safe and effective. The clinical trial deaths also highlight lingering questions about transparent reporting of adverse events to the FDA and appropriately navigating financial conflicts of interest.  Instead, numerous articles have focused on how these deaths impact the bottom line: corporate stock prices.

The excitement has been building for some time. In June 2015, MIT Technology Review described Juno’s experimental T-cell immunotherapy for leukemia as “Biotech’s Coming Cancer Cure” and profiled the “miracle” recovery of 20-year old leukemia patient Milton Wright III. Wright signed up for the clinical trial because “they hyped it up, like it was going to be amazing” and MIT Technology Review has characterized Juno’s immunotherapy trials as “remarkable.”

Some scientists are hopeful for a breakthrough, particularly for patients whose cancer has returned after multiple rounds of traditional chemotherapy. For vulnerable patients seeking a “miracle cure,” such characterizations blur the distinction between approved therapy and clinical research that may or may not produce a viable therapy. As a disclaimer, I have not seen any of the informed consent documents from Juno or Ziopharm. But whatever these documents say, media descriptions of a “coming cancer cure” make it challenging to fully convey the risks to sick people with few other options who are considering enrolling in clinical trials as a last-ditch treatment effort. This is precisely the kind of situation that the term “therapeutic misconception” addresses.

We must cautiously tread when describing Phase I and Phase II clinical trials to patients who are simultaneously acting as research subjects, and take care not to inflate our words when we discuss this research in the media. Despite the misleading name, these early gene therapy trials are not approved therapies, but experiments to assess safety, dosing tolerability, and effectiveness. The goal for this stage of research is not to provide a treatment for this specific person, but rather to contribute to generalized knowledge. It focuses on asking: Will this method of gene therapy work? Is it safe? Are there adverse risks so severe or frequent which constitute an unacceptable level of risk?

It is not clear whether the patients recognize the uncertainty of benefit, especially when measured against the magnitude of risk. Gene therapy poses a distinct, and an arguably riskier, profile of possible adverse effects compared to drugs alone because it can permanently alter the recipient’s cells and holds the potential for severe latent adverse effects such as cancer, immunologic, neurologic, and autoimmune complications.

When unexpected serious adverse reactions do occur that are related to the trial, the sponsor must report these to the FDA. Several months ago in May 2016, Juno reported one death to the FDA of a subject who was enrolled in one of its CAR-T protocols for leukemia, asserting: “It is not clear what caused the death, and a change at this time is not warranted.” In July, Juno reported two more deaths, this time stating that they resulted from compounding factors (a chemotherapy drug Fludarabine used in conjunction with the CAR-T protocol). Juno subsequently updated its statement, disclosing there have been four total deaths from its CAR-T protocols.

In response, the FDA temporarily (and very briefly) suspended the clinical trial, causing a fleeting plummet in Juno’s stock prices. Juno quickly submitted a modified protocol that removed Fludarabine, updated the trial brochure, and amended the patient consent form to the FDA. The FDA deemed these modifications acceptable and expediently lifted the hold within days, despite the alarming disclosure. Juno’s trial – and stock prices  – were back in business.  Articles (here and here) characterized these deaths and the corresponding swift response as a “bump in the road,” myopically questioning how it would impact the clinical trial progression and corporate financial outlook. Minimizing patient deaths that may have resulted from the gene therapy rather than their underlying illness is dehumanizing and ethically inappropriate, even if we reason that these patients were near the end of life.

One biotech analyst questioned FDA’s decision to quickly lift the clinical trial hold, observing, “They are trying to referee a game while the rules are still being written. And it appears to be causing some deaths that should have been avoided.”

Ziopharm made similar headlines in the past few months relating to its Phase I clinical trials designed for glioblastoma patients. Ziopharm partnered with the synthetic biology company Intrexon, and has been studying a gene therapy technique using a genetically engineered virus that is directly injected into the subject’s tumor. According to Ziopharm, the third subject died 15 days after beginning the trial of an intracranial hemorrhage. Prior to this report, two other enrolled subjects also died, albeit months after the initiation of one of the trials. According to a press release, Ziopharm maintains the intracranial hemorrhage death “is an isolated case” and the other patient deaths were unrelated, and attributed those outcomes to pre-existing illness, stating, “these patients are all, unfortunately, medically fragile.”

The problem with reporting adverse events, including deaths, to the FDA resides in a substantial loophole that awards discretion to the investigator to decide whether the adverse event is serious and whether it reasonably resulted from the gene therapy. Although the investigator theoretically stands in the best position to sort through the noise of the confounding variables of underlying illness or other drugs the subject may be taking, this nonetheless creates a troublesome reliance upon the corporation whose stock price and profitability are tenuously tied to clinical trial performance. This creates an undeniably powerful motivation to shift the blame of any adverse outcomes.

As Professor Osagie K. Obasogie has noted, profit motives remain entrenched in medical research, which can further complicate relationships where industry and medical care become intertwined. The arrangement between Ziopharm and MD Anderson Cancer Center exemplifies such enmeshment: Ziopharm and Intrexon executed a deal with MD Anderson to provide $100 million in stock, and recently appointed MD Anderson physician Dr. Laurence Cooper as Ziopharm’s newly minted CEO.  Similarly, Science’s recent profile of competitor Dr. Carl June’s work at the University of Pennsylvania also flagged the potential conflict of interest arising from its partnership with Novartis to develop gene therapies for which June would hold a financial stake arising from related patents.

Despite assertions that these relationships will be managed according to institutional conflict of interest policies, such heavy financial ties heighten the stakes and necessarily raise concerns about independent judgment and transparency. The call to uphold ethical tenets of research is nothing new, particularly when there is a frantic competition to bring an FDA-approved product to market. Back in 2007, Obasogie raised similar concerns after a patient death in a gene therapy trial for arthritis: “Time is money; in the rush to get products to market, patient safety can inadvertently take a backseat.”

These vulnerable patients have a stake, too. We must ask the right questions to see whether they appreciate the risks they decide to undertake. We must stop blindly accepting these dismissals of deaths and assurances that conflicts of interests are mitigated, especially when there is so much riding on clinical trials’ success.

 

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The Problem of Transparency and Human Genome Editing

Posted on Jun 4, 2016

 

In the past several weeks, human genetic modification has been dominating headlines.  This time, the controversy surrounded the closed door meeting between 130 scientists, attorneys, entrepreneurs, and government officials to discuss the creation of a synthetic human genome.  The project, called “Human Genome Project-Write Testing Large Synthetic Genomes in Cells” aims to synthesize a complete human genome in a cell line within ten years, with the future goal of translating such basic science into clinical applications.  Rather the modifying the human genome through editing technology such as CRISPR, synthetic creation would allow scientists to make extensive and radical changes throughout the genome.

 

According to one of the co-organizers, Harvard Geneticist George Church, the meeting merely constituted a “thought experiment” and the organizers made an executive decision to close the meeting to the public, asserting they would subsequently publish the discussion from the meeting in a prominent scientific journal that required a pre-publication embargo on publicly sharing the content of the meeting.

 

Stanford’s Drew Endy not only declined to attend based on the meeting’s intentional secrecy, but posted to his Twitter a copy of the meeting invitation, which stated the organizers instituted the media ban as a mechanism avoid media scrutiny and “to permit attendees to speak freely and candidly.”  Endy, along with Northwestern’s Laurie Zoloth published a response in Cosmos Magazine noting that “when the first people at the table mostly have significant and direct material interests in the proceeding, everyone, not just those in the room, risk out-of-control competition between public and private interests, ethical conflicts of interest, and temptations to manipulate human subject consent.”

 

Endy advocated for “pluralistic, public, and deliberative discussions” to encourage transparency of purpose and content.  Marcy Darnovsky  from The Center for Genetics and Society posited the meeting served as a step to privatize efforts toward genetic modification.  According to the Center for Genetics and Society, billionaire attorney and entrepreneur Randal Kirk plans to expand his empire of life sciences corporations focused on genetic modification (projects that currently include genetically modified salmon, genetically modified mosquitoes, and human gene therapy research) to include research projects designed to synthetically create human ova and alter the human germline.

 

We have seen the impact of closed meetings and the power by which interested stakeholders with deep pockets and a vested interest in promoting a technology can direct public opinion like a puppet master through strategic media campaigns, assert “conclusions” professing basis in scientific evidence, proclaim consensus despite the existence of divisive questions within the scientific community, and strong arm regulation and policy without public transparency.  Perhaps most problematically, few members of the public are even aware of this complex history behind the curtain of genetically modified food so eloquently and meticulously presented by attorney Steven Druker in Altered Genes, Twisted Truth In his book, Druker raises several notable points, each of which are pertinent to the discussion relating to human genetic modification: we must analytically examine the current state of science rather than accepting inflated promises, comprehend the danger of failing to consider unintended effects within the organism and its ecosystem, and scrutinize the implication of inherent unpredictability when altering genetic structures.

 

Indeed, the Committee on Science Technology, and Law Policy and Global Affairs at the International Summit on Human Gene Editing noted that the current gene editing technology CRISPR is highly unpredictable: it can alter DNA at other unintended locations other than its target, which would impact genetic structure and function at other locations on the genome.  This process could activate other genes including cancer causing genes,  inactivate essential genes, or cause chromosomal rearrangements.  One team from Guangzhou Medical University China who conducted gene editing on non-implantable embryos using CRISPR reported dismal preliminary results: only 4 of the 26 embryos the team used produced the desired mutation that scientists believe confers HIV resistance and the embryos demonstrated signs of mosaicism.  Furthermore, Geneticist Eric Lander observed inducing this particular mutation simultaneously confers an increased risk of West Nile virus and aptly summarized: “We are terrible predictors of the consequences of the changes we make…we don’t understand the genome enough to make changes in the long run.”

 

Despite a United Nations prohibition on the modification of the human genome and other nations that legally prohibit human genetic modification, the US does not have federal regulations prohibiting human genetic modification, whether achieved through genome editing or synthetic human genome creation.  It is also foreseeable that any obstacles arising out of federal funding limitations could be easily circumvented though private funding or successful lobbying to ease or even erase such restrictions.

 

This weekend at the American Society of Law, Medicine and Ethics Annual Heath Law Professors Conference Law Professor John Robertson repeated Church’s label, asserting that we are likely to see “exciting” efforts to “correct disease” fairly soon but efforts for enhancement are a distant “thought experiment.”  I disagree.   Corporations need not offer perfectly accurate technology, but instead appeal to a market by advertising a product’s technological promise.  As we’ve seen in current genomic technologies, this translates into technology premised upon manufacturer advertisements of accuracy and validity which may or may not produce the desired advertised outcome.

 

The community of interested stakeholders must rise as a leader to promote thoughtful governance, particularly given the transnational and global nature of this research.  Public transparency of the scientific community’s goals and agendas are imperative given our current juncture-  private corporations are poised to create synthetic ova, presently occurring experiments create chimeras integrating human DNA into animals, and Bill Skarnes of the Wellcome Trust Sanger Institute predicts the utilization of human genetic modification for clinical use in humans within the next five years.  Failing to intervene with prudent regulation at this juncture will have unimaginable and irreversible consequences.

 

 

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Media Misstates the Message: Investigate CDC Whistleblower’s Claims

Posted on Apr 22, 2016

Media headlines are abuzz around the decision to pull the documentary Vaxxed: from Conspiracy to Cover-Up from the Tribeca Film Festival.  As a disclaimer, I have not viewed the film.  What is deeply troubling, however, is how numerous media outlets (here and here) have misconstrued the film’s message calling for an examination of vaccine safety and efficacy.  Instead, headlines and news content repeat erroneous assertions that are contrary to scientific evidence and focus exclusively on the controversial Dr. Andrew Wakefield as a red herring. (If you are interested in learning the full story about the Wakefield controversy and the role of the media, you can read it in this book).   Both the science and the law relating to vaccination are nuanced and evolving.  When vaccines go through the approval process at the FDA, approval is premised upon data submitted by the vaccine manufacturer showing that the product is safe, effective, and its benefits outweigh the risks.  Glossing over this complex process and improperly labeling any questions pertaining to safety and efficacy as “anti-vaccine” effectively stunts the scientific process as an evolution and pursuit of developing knowledge.

Based on its website, the film intends to address statements made by Dr. William Thomson PhD, senior scientist at the CDC who revealed he was instructed by fellow CDC senior scientists to eliminate highly unfavorable data from studies they conducted examining links between vaccination and neurological injury.  The conclusions of these studies (DeStefano 2004, Thompson 2007,  Price 2010)  have been widely cited and touted by Dr. Paul Offit MD as “definitive” proof demonstrating vaccine safety.  What did that excluded data show?  According to conversations between Thompson and biology Professor Dr. Brian Hooker PhD, the data demonstrated a substantial differential rate of adverse reactions to the MMR vaccine based on sex and race: African American boys who received the vaccine according to the American Academy of Pediatric Schedule had a 3.4 fold increase in risk of autism.  Barry published a book summarizing conversations he had with Thompson including full transcripts of lengthy discussions related to alleged data manipulation and conflicts of interest between industry and the CDC.  You can read a summary written by attorney Robert Kennedy Jr. JD LLM here and the book containing full transcripts here.

Not only is this statistic alarming, but what’s more concerning is lack of mainstream media coverage and public knowledge of this incident and other information that calls into questions vaccine safety from a variety of angles.    CBS Reporter Sharyl Attkisson has referred to the topic of vaccine safety and efficacy as the “most censored and misreported story of the century.” To find that information requires digging through other media channels, such as Attkisson’s website, attorney Robert Kennedy Jr. JD LLM’s work, MIT Senior Research Scientist Stephanie Seneff PhD’s findings, or assessments by physicians Dr. Mark Hyman MD and  Dr. Kelly Brogan MD.

Combing through the research rather than accepting the common meme reveals numerous safety questions about which there has been no open dialogue pertaining to studies demonstrating: long term central nervous system damage including seizures, learning disabilities, and neurological disorders; an increased risk of severe allergies and asthma; the onset of chronic arthritis; and death.  Further, numerous studies (examples here and here) and federal whistleblower claims against Merck point to compelling evidence undermining assumptions of efficacy and the veracity of manufacturer claims of efficacy prior to FDA submission for approval.  Such evidence threatens the massive profits of the global vaccine market, which constituted estimated $24 billion in 2014 (see here and here).

As New York University School of Law Research Scholar Mary Holland JD has noted, the law recognizes vaccines’ risks despite appropriate manufacturing and administration.  Vaccines are classified as “unavoidably unsafe” products; that is, they will necessarily expose some individuals to risk of injury and death.  In 1986 Congress passed the National Childhood Vaccine Injury Act as a means to shield manufacturers from mounting liability claims via private litigation while compensating victims of vaccine injury.  In 2011,  the Supreme Court in Bruesewitz v. Wyeth held that the Act preempts all design-defect claims against vaccine manufacturers, which precludes injured parties from seeking private remedy from the manufacturer.

In a powerful dissent, Justice Sotomayor stated:

“Vaccine manufacturers have long been subject to a legal duty, rooted in basic principles of products liability law, to improve the designs of their vaccines in light of advances in science and technology… the majority’s decision leaves a regulatory vacuum in which no one—neither the FDA nor any other federal agency, nor state and federal juries—ensures that vaccine manufacturers adequately take account of scientific and technological advancements. This concern is especially acute with respect to vaccines that have already been released and marketed to the public. Manufacturers, given the lack of robust competition in the vaccine market, will often have little or no incentive to improve the designs of vaccines that are already generating significant profit margins.”

Excluding information such as Thompson’s allegations from both public and policy discussions has implications for determining the extent and acceptability of risk for adverse events.  Notably, it also disables consideration of the risk of adverse events based on distinct classes and differential responses based on sex, genetic variation, or use during pregnancy.  FDA’s regulatory structure assumes that until a vaccine is given to the general population, all potential adverse events cannot be anticipated.  Many vaccines undergo Phase IV studies and the FDA relies upon the Vaccine Adverse Event Reporting System (VAERS) to identify adverse events after marketing begins.  According to former FDA Commissioner Dr. David Kessler MD, since VAERS’s inception in 1990 about 35.2 million adverse events have been reported, yet Kessler estimated only this accounts for only 1% of all serious adverse events that occurred.

Without an open and frank conversation about the meaning of evidence demonstrating increased risks or decreased efficacy, we face as a society troubling public health implications for which as Justice Sotomayor warned,  no one will be held accountable.

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