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Research Ethics

Advances in Neuroscience Strengthen Ethical Opposition to Harmful Experiments on Dogs

2 Aug, 17 | by miriamwood

Guest Post: Jarrod Bailey, Cruelty Free International, London, UK.

Paper: Advances in Neuroscience Imply that Harmful Experiments in Dogs are Unethical

More than 200,000 dogs are used in harmful experiments every year worldwide, in research into human and animal diseases and in the testing of new drugs and agrochemicals. This continues despite significant public opposition to it, and of increasing scientific evidence of its poor human relevance and misleading nature. From a utilitarian perspective, these alter the harm-to-benefit balance of using dogs in experiments. If experiments on dogs cause more suffering than is commonly appreciated, and if they are not delivering the human benefits that are claimed of them, then these experiments must be reconsidered by those who fund, license, and conduct them.

But how do we know how much dogs can suffer, and how much joy they can experience and are thus deprived of in a laboratory? Many would argue that it is simply obvious that dogs have impressive cognitive capabilities, as well as experiencing positive and negative emotions. This is not enough for science, of course, which seems unable or unwilling to accept sentience in nonhumans as it does for humans, based on weight of evidence. For many years, efforts to understand the minds of dogs in more detail have centred on ethological research which, while extremely valuable, does have some associated, widely acknowledged caveats. It can only go so far, especially for those for whom the evidence it produces can perhaps never be sufficient to warrant a change of attitude and behaviour towards dogs.

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Can We Trust Research in Science and Medicine?

26 Jul, 17 | by bearp

By Brian D. Earp  (@briandavidearp)

Readers of the JME Blog might be interested in this series of short videos in which I discuss some of the major ongoing problems with research ethics and publication integrity in science and medicine. How much of the published literature is trustworthy? Why is peer review such a poor quality control mechanism? How can we judge whether someone is really an expert in a scientific area? What happens when empirical research gets polarized? Most of these are short – just a few minutes. Links below:

Why most published research probably is false

The politicization of science and the problem of expertise

Science’s publication bias problem – why negative results are important

Getting beyond accusations of being either “pro-science” or “anti-science”

Are we all scientific experts now? When to be skeptical about scientific claims, and when to defer to experts

Predatory open access publishers and why peer review is broken

The future of scientific peer review

Sloppy science going on at the CDC and WHO

Dogmas in science – how do they form?

Please note: this post will be cross-published with the Practical Ethics blog. 

Not Just About Consent: The Ethical Dimensions of Research Methodology Knowledge in IRBs

15 Jun, 17 | by bearp

Guest Post: Sarah Wieten

The recent article, “Some Social Scientists Are Tired of Asking for Permission” in the New York Times inspired a great deal of debate about the role of institutional research ethics board (IRB) oversight in social science, which some argue is in most cases unlikely to involve significant harm to participants.

While the role IRBs play in sociological research is being re-examined, the importance of IRB oversight for medical research was not similarly called into question. But what exactly does IRB oversight in medical research involve? Should these groups be content with assuring that patients and participants in medical research have provided informed consent? Or do they have wider duties? What is the relationship between methodologically rigorous science and ethical science?

The approval of research projects by IRBs is an integral part of the conduct of research in universities. IRBs ensure that all research follows key ethical guidelines and is pursued for good reason, and in doing so, they aim to keep patients and participants out of harm’s way. IRBs are important gatekeepers of institutional research, and serve as a check on the work of scientists, physicians, and others who are pursuing new knowledge.

We would assume then, that people serving on IRBs have a clear understanding of relevant research design. That way, they can check the research for ethical issues stemming from the methodology. They can also make sure that methodologically poor studies do not proceed, as this would be an unethical waste of resources (and would put participants at risk without a reasonable prospect of gaining reliable knowledge in exchange).

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“NOW’s interest in pharmaceutical gender equity seems to have disappeared with its funding.”

15 Jun, 17 | by Iain Brassington

There’s a remarkable piece on the Hastings Center’s blog by Alycia Hogenmiller about a drug called Addyi.  Addyi is a drug that doesn’t work to treat a condition that doesn’t exist, pushed by campaigners who are actually industry shills.

Sprout Pharmaceuticals, run by Cindy and Robert Whitehead, was determined to obtain regulatory approval for flibanserin (Addyi), an antidepressant-turned-aphrodisiac that had already twice failed to gain approval by the FDA.  To create this fake feminist campaign, Sprout hired Blue Engine Media, a PR firm that created a sham organization called Even the Score. The campaign hired two feminists: a former director of the FDA Office of Women’s Health, and the former president of the Women’s Research and Education Institute – both well-known to women’s groups.  Even the Score recruited and paid consumer advocacy groups to pressure the FDA into approving flibanserin for Hypoactive Sexual Desire Disorder – a condition previously created by industry to sell another drug.

I want to know more about those people hired.  What were they thinking?  What did they think they were doing?  What weren’t they thinking?

It’s sad to see advocacy groups become mouthpieces for pharma.  It is even sadder when those mouthpieces are feminist groups that should be protecting the interest of women but instead are protecting a company’s bottom line.  Every single one of the advocacy groups that don’t take money from pharmaceutical companies opposed Addyi’s approval and use.  For example, the National Women’s Health Network, the Jacobs Institute for Women’s Health, the National Center for Health Research, the Reproductive Health Technologies Project, and the New View campaign all publicly opposed the drug before and after approval.  “This decision to approve flibanserin is a triumph of marketing over science,” said Cindy Pearson, head of the National Women’s Health Network.

[…]

Addyi was never a true symbol for gender equity.  The drug doesn’t work well and was never safe.

Just roll back a bit…

Every single one of the advocacy groups that don’t take money from pharmaceutical companies opposed Addyi’s approval and use.

Whoa.

Several lessons can be learned from the story of Even the Score.  First, don’t trust, support, or listen to purported consumer advocacy groups that take money from pharmaceutical companies.

D’ya reckon?

Go and read the whole thing.  It’s astonishing.

The conference in respect of which the post is written looks good, too.

A Plutocratic Proposal: An Ethical Way for Rich Patients to Pay for a Place on a Clinical Trial

8 Jun, 17 | by miriamwood

Guest Post: Alexander Masters and Dominic Nutt
Paper: A Plutocratic Proposal: an ethical way for rich patients to pay for a place on a clinical trial

Is it ethically possible to fund a clinical trial by charging the participants?  We believe we have discovered a way to do it.  Our suggested method has, as far as we know, never been proposed before.

In A Plutocratic Proposal: an ethical way for rich patients to pay for a place on a clinical trial we show how the system could work and argue that all the usual and obvious objections to patient-funded clinical research do not apply in this case; indeed, in several respects the Plutocratic Proposal is more ethical than established methods of funding human experiments.  Furthermore, we believe the Plutocratic Proposal will provide new money for research, particularly for neglected research into rare diseases; it will not deplete the already limited resources of traditional funders.

The ‘usual ethical objections’ include such points as:

  • paying participants could be exploited by research teams desperate to run their trials;
  • research teams might bend their inclusion criteria to accommodate rich patients and so encourage bad science;
  • by enabling research groups to charge patients directly, they can bypass the peer review process and so promote quack ideas;
  • paying patients will attempt to buy their way off concurrent comparison wings, which is not only ethically but scientifically ruinous.

How can a patient-financed funding scheme overcome such fundamental and, until now, apparently insuperable ethical objections?  Read the paper to find out

Breakthrough Immunotherapies Seem Like a Dream Come True for Children with Leukemia

18 Apr, 17 | by miriamwood

Guest Post: Nancy Jecker, Aaron Wightman, Abby Rosenberg, Doug Diekema

Paper: From protection to entitlement: selecting research subjects for early phase clinical trials involving breakthrough therapies

A breakthrough therapy to cure cancer in children suffering from acute lymphoblastic leukemia (ALL) is a dream for many families.  New immunotherapies appear to make this dream a reality. Such therapies use a person’s own immune cells to recognize and combat their disease. In the largest study to date of ALL patients treated with a form of immunotherapy known as Chimeric Antigen Receptor (CAR) T-Cell therapy, a 93% remission rate was reported. Such results are a glimmer of hope for those whose prognoses were previously considered very poor.

However, the good news is tempered by the fact this potentially lifesaving experimental therapy may not be available to everyone who might benefit. And demand is growing as word spreads. Since CAR T-cell therapy for ALL is available only through clinical trials, do patients have a right to participate? How should we choose among medically suitable candidates?

We have faced these questions before. Most recently, with ZMapp to treat Ebola Virus Disease, azidothymidine (AZT) to treat HIV and AIDS, and Immunitab (Gleevac) to treat Chronic Myleogenous Leukemia. Are patients suffering from devastating, life-threatening diseases entitled to breakthrough therapies?

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Individually-Randomized Controlled Trials of Vaccines Against the Next Outbreak

11 Apr, 17 | by miriamwood

Guest Post: Nir Eyal, Marc Lipsitch

Paper: Vaccine testing for emerging infections: the case for individual randomisation 

The humbling experience of international response to Ebola taught the world a thing or two on preparing for Zika and for other emerging infections.

Some of those lessons pertain to vaccine development against emerging infections. One lesson was that vigorous vaccine development should start long in advance of outbreaks. CEPI, the Coalition for Epidemic Preparedness Innovations, was recently launched with an initial investment of half a billion US dollars from the Gates Foundation, Britain’s Wellcome Trust and the governments of Japan, Norway and Germany. There is also growing recognition that best practices on vaccine testing should be developed prior to outbreaks, from a study methodology viewpoint.

By contrast, in Zika, ethical guidelines on response in general and on an aspect of vaccine testing were created only once the pandemic erupted. Shouldn’t ethical disputes, e.g. on trial design for vaccine candidates, be ironed out in advance of emerging infections?

One persistent ethical question in vaccine testing pertains to individually-randomized control in efficacy trials. At the height of the 2014-5 Ebola outbreak, individually-randomized controlled trials were much maligned. Our paper at the Journal of Medical Ethics sets out to defend that approach for vaccine efficacy testing in emerging infections, including highly fatal and untreatable ones in developing countries.

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The Deadly Business of an Unregulated Global Stem Cell Market

30 Mar, 17 | by miriamwood

Guest Post: The deadly business of an unregulated global stem cell industry

Tereza Hendl and Tamra Lysaght

In our paper, we report on the case of a 75-year old Australian woman who died in December 2013 from complications of an autologous stem cell procedure. This case was tragic and worth reporting to the medical ethics community because her death was entirely avoidable and the result of a pernicious global problem – doctors exploiting regulatory systems in order to sell unproven and unjustified stem cell interventions.

The patient at the centre of this case, Sheila Drysdale, underwent a liposuction procedure administered by cosmetic surgeon, Dr Ralph Bright, at his private Sydney clinic. Dr Bright did not perform this procedure for cosmetic reasons, but rather to ‘treat’ her advanced dementia with adipose (fat) derived stem cells. Mrs Drysdale died within ten hours of the surgery. Following an inquest into her death, the New South Wales Deputy Coroner stated that the utilisation of stem cells to ‘treat’ dementia was “highly questionable” and displayed “some of the hallmarks of ‘quack’ medicine,” particularly owing to the lack of scientific evidence supporting such ’therapy.’ The Coroner, thus, called for a more rigorous regulation of ‘innovative’ medical procedures in Australia that would protect vulnerable patients. Sadly, the relevant regulatory authorities have done very little to bring about any justice for Mrs Drysdale, or to address the systemic problems in Australia’s legislative framework that allows medical professionals to offer unproven stem cell-based interventions to patients without any accountability.

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How to Keep HIV Cure-Related Trials Ethical: The Benefit/Risk Ratio Challenge

20 Feb, 17 | by bearp

Guest Post by Nir Eyal

Re: Special Issue of the Journal of Medical Ethics on the ethics and challenges of an HIV cure

For most patients with HIV who have access to antiretroviral treatment and use it properly, that treatment works well. But the holy grail of HIV research remains finding a cure. Sometimes that means a literal, sterilizing cure that would remove HIV from the body. But increasingly the aim is to find a mere functional cure that would send HIV into sustained remission during which antiretrovirals would be unnecessary.

Early successes in cure-related research, most notably the apparent cure of ‘Berlin patient’ Timothy Brown, prompted the International AIDS Society and the US National Institutes of Health to declare cure-related research a high priority. Recent successes in animal models have re-kindled hopes, and cure-related research is ongoing.

But there is a catch. Many of the early-phase cure-related studies that are currently planned or under way carry risks that are either very high or hard to quantify. These risks come from toxicity (e.g., of stem cell transplantation in an immunocompromised population), necessary interruptions to antiretroviral treatment (either short ‘pauses’ or intentionally longer breaks), or invasive physical exams. They affect study subjects and, sometimes, third parties like sexual partners or foetuses.

While high or unknown risks are a mainstay of early-phase trials in areas like cancer research, cure study participants typically have a safe and efficacious alternative to those risks: remaining on antiretrovirals. Can we justify asking patients who are doing well on antiretrovirals to accept the risk and uncertainty of many HIV cure-related trials? If we cannot, we might need to give up on the hope of curing HIV, or of achieving controlled remission.

These ethical questions about HIV cure-related trials were first raised by an activist, then asked again and again. They also arise in human subject research beyond HIV cure-related studies: what should we do when it is hard to keep a socially-important study beneficial in prospect to study participants? Are we ever permitted to compromise the individual’s objective interests in the pursuit of collective goals? What are legitimate ways of pre-empting this dilemma? The entire February 2017 issue of Journal of Medical Ethics is dedicated to clarifying and trying to answer these questions.

After an introduction, the journal issue provides a background by leading HIV-cure related researchers Dan Kuritzkes and Kenneth Freedberg and Paul Sax, as well as myself, a philosopher. Articles by legally-trained bioethicists Rebecca Dresser and Seema Shah and philosopher Caspar Hare suggest ways to quantify and mitigate risks to participants of cure-related studies. Contributions by philosopher Lara Buchak, bioethicist and lawyer Emily Largent, and AIDS activist David Evans assess how much the potential benefits to study participants, ranging from the remote hope of being cured through financial incentives to the satisfaction of having helped others, can legitimately offset any remaining risks. Legally-trained bioethicist George Annas and philosopher Danielle Bromwich explore how much participants’ fully informed consent can count as ample protection in cure-related studies, and when that consent counts as full. Philosophers Dan Wikler, Nick Evans (with first author public health expert Regina Brown), Rahul Kumar, and Frances Kamm assess when, if ever, the potential public health benefits of research—e.g., finding a cure for HIV—can warrant placing individual study participants at high net risk. An afterword asks how these investigations should affect future directions in research ethics.

Many contributions agree that myriad ways exist to justify studies that, at least on the face of it, run counter to the best medical interests of candidate participants. Furthermore, one need not be a utilitarian to argue as much. Even so-called contractualist ethicists such as Rahul Kumar can justify such studies, provocative though they may be for current culture in clinical study oversight. That culture, these articles suggest, is hard to defend from a wide spectrum of ethical theories.

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NOTE: This post will be cross-published at BMJ Opinion.

HIV Cure Research and The Dual Aims of the Informed Consent Process

25 Jan, 17 | by miriamwood

Guest Post: Danielle Bromwich and Joseph Millum

Paper: Informed Consent to HIV Research 

Special Issue: The benefit/risk ratio challenge in clinical research, and the case of HIV cure

A cure for HIV would be tremendously valuable. Approximately 37 million people worldwide are HIV-positive and 15 million are currently on antiretroviral therapy. Until recently it was assumed that this therapy would be the extent of HIV treatment and that those with access to it would need to take their drugs for life. But what once seemed impossible is now in early phase clinical trials: interventions designed to completely eradicate HIV from the immune system.

Excitement surrounding these “HIV cure” studies is tempered by ethical concern. They require participants to come off their antiretroviral therapy and undergo highly risky interventions using gene transfers or stem cell therapy. These are currently proof of concept studies—no one expects the participants to be cured. Their purpose is to provide essential information about safety and pharmacokinetics, but in doing so they expose participants to high risks with little prospect of direct benefit.

If we could be confident that participants understood their trials’ true risk-benefit ratio, these high risks might be less troubling. But such confidence would be misplaced. Decades of data show poor comprehension of risk among participants in clinical trials. The fact that HIV is still a stigmatized condition amplifies this concern. Potential participants may be desperate to be rid of their disease and so downplay the risks and exaggerate the potential benefits. Understandably, HIV cure researchers and research ethics committees are worried. What should they do with a patient-participant who wants to come off his medication and receive a high-risk experimental intervention because he thinks that he’ll be “the one” who is cured?

Informed consent is generally thought to be one key protection for participants enrolled in risky studies. The standard view of informed consent says that valid consent requires the person giving consent to understand the risks and benefits of study participation. According to this view, someone who seriously misunderstands the study’s true risk-benefit ratio can be excluded on the grounds that he has not given valid consent to study participation.

In a recent paper, part of a special collection on HIV cure research in the Journal of Medical Ethics, we analyze a range of concerns about informed consent for HIV cure trials.

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