First CRISPR trial in humans is reported to start August 2016

By Sharon Begley @sxbegle
Stat News
Originally published July 21, 2016

Scientists in China plan to use the genome-editing technology CRISPR-Cas9 in patients as early as next month, Nature reported on Thursday. If they go ahead, it would be the first time people would be injected with cells whose DNA has been altered by CRISPR.

A US proposal to run a similar study received approval by a federal ethics and safety panel last month, but it faces months of additional regulatory hurdles before it can go ahead by the end of 2016 at the earliest. The Chinese scientists, led by oncologist Lu You of Sichuan University’s West China Hospital in Chengdu, received approval from the hospital’s review board on July 6, Nature reported, and plan to treat their first patient in August.

Both the US and Chinese scientists would use CRISPR to edit immune-system T cells in patients with cancer in an effort to make those cells destroy malignant cells.

The article is here.

French drug trial leaves one brain dead and five critically ill

By Angelique Chrisafis
The Guardian
Originally published January 15, 2916

Here is an excerpt:

Touraine said the study was a phase one clinical trial, in which healthy volunteers take the medication to “evaluate the safety of its use, tolerance and pharmacological profile of the molecule”.

Medical trials typically have three phases to assess a new drug or device for safety and effectiveness. Phase one entails a small group of volunteers and focuses only on safety. Phase two and three are progressively larger trials to assess the drug’s effectiveness, although safety remains paramount.

Testing had already been carried out on animals, including chimpanzees, starting in July, Touraine said.

Bial said it was committed to ensuring the wellbeing of test participants and was working with authorities to discover the cause of the injuries, adding that the clinical trial had been approved by French regulators.

The story is here.

Informed Consent and Standard of Care: What Must Be Disclosed

Ruth Macklin & Lois Shepherd
The American Journal of Bioethics
Volume 13, Issue 12, 2013

Abstract

The Office for Human Research Protections (OHRP) was correct in determining that the consent forms for the National Institutes of Health (NIH)-sponsored SUPPORT study were seriously flawed. Several articles defended the consent forms and criticized the OHRP's actions. Disagreement focuses on three central issues: (1) how risks and benefits should be described in informed consent documents; (2) the meaning and application of the concept of “standard of care” in the context of research; and (3) the proper role of OHRP. Examination of the consent forms reveals that they failed to disclose the reasonably foreseeable risks of the experimental interventions in the study, as well as the potential for differences in the degree of risk between these interventions. Although the concept of “standard of care” may be helpful in determining the ethical acceptability of other aspects of research, such as clinical equipoise, it is not helpful in discussing consent requirements.

The entire article is here.

Guatemalans deliberately infected with STDs sue Johns Hopkins

By Oliver Laughland
The Guardian
Originally posted April 2, 2015

Nearly 800 plaintiffs have launched a billion-dollar lawsuit against Johns Hopkins University over its alleged role in the deliberate infection of hundreds of vulnerable Guatemalans with sexually transmitted diseases, including syphilis and gonorrhea, during a medical experiment programme in the 1940s and 1950s.

The lawsuit, which also names the philanthropic Rockefeller Foundation, alleges that both institutions helped “design, support, encourage and finance” the experiments by employing scientists and physicians involved in the tests, which were designed to ascertain if penicillin could prevent the diseases.

The entire article is here.

The Best-Selling, Billion-Dollar Pills Tested on Homeless People

How the destitute and the mentally ill are being used as human lab rats

by Carl Elliott
Matter
Originally posted on July 27, 2014

Here are two excerpts:

If you’re looking for poor people who have been paid to test experimental drugs, Philadelphia is a good place to start. The city is home to five medical schools, and pharmaceutical and drug-testing companies line a corridor that stretches northeast into New Jersey. It also has one of the most visible homeless populations in the country. In Philly, homeless people seem to be everywhere: sleeping in Love Park, slumped on benches in Suburban Station, or gathered along the Benjamin Franklin Parkway, waiting for the free meals that a local church gives out on Saturdays.

(cut)

Not long ago, such offers would have been considered unethical. Paying any volunteer was seen as problematic, even more so if the subjects were poor, uninsured, and compromised by illness. Payment, it was argued, might tempt vulnerable subjects to risk their health. As trials have moved into the private sector, this ethical calculus has changed. First came a hike in the sums that volunteers could be paid: Many clinical trial sites now offer over $6,000 for an inpatient drug study. Eligibility requirements have changed, too. For years, trial sites paid only healthy volunteers, mainly to test new drugs for safety. These days people with asthma, diabetes, kidney disease, liver disease, and other conditions can be paid take part in trials.

The entire article is here.

Ethics is for human subjects too: Participant perspectives on responsibility in health research

By Susan Cox and Michael McDonald
Social Science & Medicine
Volume 98, December 2013, Pages 224–231

Abstract

Despite the significant literature as well as energy devoted to ethical review of research involving human subjects, little attention has been given to understanding the experiences of those who volunteer as human subjects. Why and how do they decide to participate in research? Is research participation viewed as a form of social responsibility or as a way of obtaining individual benefits? What if anything do research subjects feel they are owed for participation? And what do they feel that they owe the researcher? Drawing on in-depth individual interviews conducted in 2006 and 2007 with 41 subjects who participated in a variety of types of health research in Canada, this paper focuses on subject perspectives on responsibility in research. Highlighting the range of ways that subjects describe their involvement in research and commitments to being a ‘good’ subject, we present a typology of narratives that sheds new light on the diverse meanings of research participation. These narratives are not mutually exclusive or prescriptive but are presented as ideal types typifying a set of circumstances and values. As such, they collectively illuminate a range of motivations expressed by human subjects as well as potential sources of vulnerability. The typology adds a new dimension to the literature in this area and has significant implications for researchers seeking more human-subject centred approaches to research recruitment and retention, as well as research ethics boards trying to better anticipate the perspectives of prospective participants.

Highlights

• Participant responsibility is a neglected aspect of research ethics.
• Responsibility can be conceptualized according to degree of agency and altruism.
• Participants' narrative accounts yield four main orientations to responsibility.
• These reveal differing motivations and sources of vulnerability.

The entire article is here.

Harvard Researchers Used Secret Cameras to Study Attendance. Was That Unethical?

By Rebecca Koenig and Steve Kolowich
The Chronicle of Higher Education
Originally published November 6, 2014

A high-tech effort to study classroom attendance at Harvard University that used secret photo surveillance is raising questions about research ethics among the institution’s faculty members. The controversy heated up on Tuesday night, when a computer-science professor, Harry R. Lewis, questioned the study at a faculty meeting.

During the study, which took place in the spring of 2013, cameras in 10 Harvard classrooms recorded one image per minute, and the photographs were scanned to determine which seats were filled.

To some professors, it was an obvious intrusion into their privacy—and their students’.

The entire article is here.

Human-subjects research: The ethics squad

By Elie Golgin
Nature
Originally published October 21, 2014

Here is an excerpt:

Ethical dilemmas in research are nothing new; what is new is that scientists can go to formal ethics consultancies such as Silber's to get advice. Unlike the standard way that scientists receive ethical guidance, through institutional review boards (IRBs), these services offer non-binding counsel. And because they do not form part of the regulatory process, they can weigh in on a wider range of issues — from mundane matters of informed consent and study protocol to controversial topics such as the use of experimental Ebola treatments — and offer more creative solutions.

The consulting services are “a really new area”, says Joshua Crites, a research ethicist at the Pennsylvania State College of Medicine in Hershey. “Even some of the most basic questions get complicated really quickly, and it's better to have a group of ethicists working together to sort this out.”

The entire article is here.

U.S Troops and Patients Were Used as Malaria Guinea Pigs

By Bill Briggs
NBC News

Tens of thousands of mental patients and troops unknowingly became malaria test subjects during the 1940s — part of a secret federal rush to cure a dread disease and win a world war, according to a book published Tuesday that exposes vast, previously unknown breaches of medical ethics.

“The Malaria Project” — operating via the same covert White House machinery that drove the Manhattan Project — tasked doctors with removing malaria from naturally exposed U.S. troops then injecting those strains into people with syphilis and schizophrenia, reports author Karen Masterson, who researched files at the National Archives.

Some details of the project have been previously reported, but the book's new revelations renew debate over the ethics of using unsuspecting people as test subjects — similar to the Tuskegee Syphilis Study on low-income black men.

The entire story is here.

This will hurt a bit

By David Hunter
BMJ Group Blogs
Originally posted April 11, 2014

Here is an excerpt:

In this piece she describes the case of a Cornell graduate student who carried out a piece of self-experimentation without IRB approval (based on the mistaken belief it wasn’t required) which aimed to assess which part of the body was worst to be stung by a bee on and involved:  ”five stings a day, always between 9 and 10am, and always starting and ending with “test stings” on his forearm to calibrate the ratings. He kept this up for 38 days, stinging himself three times each on 25 different body parts.”

The entire blog is here.

World Medical Association Declaration of Helsinki

Ethical Principles for Medical Research Involving Human Subjects
World Medical Association
JAMA. Published online October 19, 2013. doi:10.1001/jama.2013.281053

Preamble

1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human subjects, including research on identifiable human material and data.

The Declaration is intended to be read as a whole and each of its constituent paragraphs should be applied with consideration of all other relevant paragraphs.

2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. The WMA encourages others who are involved in medical research involving human subjects to adopt these principles.

The entire document is here.

Human Subjects Research Landscape Project – Analysis Dataset

The Presidential Commission for the Study of Bioethics

In order to respond to President Obama’s November 24, 2010 charge “to determine if Federal regulations and international standards adequately guard the health and well-being of participants in scientific studies supported by the Federal Government,” the Commission recognized that a critical first step would be to define and understand the landscape of “scientific studies supported by the Federal Government.” Finding no comprehensive publicly available source for this information, the Commission asked the 18 federal departments and agencies that have adopted the Common Rule—and therefore were likely to support scientific studies with human subjects—to provide basic project-level data for department/agency-supported human subjects research in Fiscal Year 2006 to Fiscal Year 2010.

These data, which include study title, number and location of sites, number of subjects, and funding information, were compiled into the Commission’s Research Project Database, and analyzed as part of its Human Subjects Research Landscape Project.

Posted here is the Commission’s analysis dataset, which incorporates minimal data cleaning as detailed in “Appendix II: Human Subjects Research Landscape Project Methods.”  Also posted is a data dictionary that defines the dataset’s fields. The data are available in two formats: Microsoft Access and .CSV.  The Access file contains the same information as the three .CSV files.

As detailed in the Methods, department/agency-reported information in the dataset was not independently audited or verified.  Moreover, the dataset is static; no additional data will be added to it.

For further information, and to read the Human Subjects Research Landscape Project Methods, please see “Appendix I: Human Subjects Research Landscape Project: Scope and Volume of Federally Supported Human Subjects Research” and “Appendix II: Human Subjects Research Landscape Project Methods.”

The entire study is here.

Experts propose overhaul of ethics oversight of research

The Hastings Center
Press Release
Originally released January 2013

Hastings Center Special Report aims to 'provoke a national conversation'

The longstanding ethical framework for protecting human volunteers in medical research needs to be replaced because it is outdated and can impede efforts to improve health care quality, assert leaders in bioethics, medicine, and health policy in two companion articles in a Hastings Center Report special report, "Ethical Oversight of Learning Health Care Systems." One of the authors calling for a new approach is the main architect of the current ethical framework.

Seven commentaries in the publication, written by leaders with national responsibility for ethical oversight of medical research and efforts to improve health care quality, find areas of agreement and offer critiques.

In an accompanying editorial, co-guest editors Mildred Z. Solomon, President of The Hastings Center and Ann C. Bonham, Chief Scientific Officer at the American Association of Medical Colleges, wrote that by inviting these commentaries, they aimed to "provoke a national conversation." According to Solomon, "The challenge is to design oversight that adequately protects patients without impeding the kinds of data collection activities we need to improve health care quality, reduce disparities, and bring down our rate of medical errors." (See video of Dr. Solomon on the importance of this debate.)

For nearly four decades, protection of human participants in medical research has been based on the premise that there is a clear line between medical research and medical treatment. But, the two feature articles argue, that distinction has become blurred now that health care systems across the country are beginning to collect data from patients when they come in for treatment or follow-up. The Institute of Medicine has recommended that health care organizations do this kind of research, calling on them to become "learning health care systems."

In particular, the articles challenge the prevailing view that participating in medical research is inherently riskier and provides less benefit than receiving medical care. They point out that more than half of medical treatments lack evidence of effectiveness, putting patients at risk of harm. On the other hand, some kinds of clinical research are no riskier than clinical care and are potentially more beneficial; an example is comparative effectiveness research to find out which of two or more widely used interventions for a particular condition works best for which patients.

"Relying on this faulty research-practice distinction as the criterion that triggers ethical oversight has resulted in two major problems," the authors write. First, it has led to "delays, confusion, and frustrations in the regulatory environment" when institutional review boards, which are responsible for the ethical oversight of research with human subjects, have difficulty distinguishing between research and clinical practice. Second, it has "resulted in a morally questionable public policy in which many patients are either underprotected from clinical practice risks (when exposed to interventions of unproven effectiveness or to risks of medical error) or overprotected from learning activities that are of low risk . . . and that stand to contribute to improving health care safety, effectiveness, and value."

The authors call for a new ethical framework that "is commensurate with the risk and burden in both realms." Their second article outlines such a framework for determining the type and level of oversight needed for a learning health care system. The basic structure consists of seven obligations: 1) to respect the rights and dignity of patients; 2) to respect the clinical judgment of clinicians; 3) to provide optimal care to each patient; 4) to avoid imposing nonclinical risks and burdens on patients; 5) to reduce health inequalities among populations; 6) to conduct responsible activities that foster learning from clinical care and clinical information; and 7) to contribute to the common purpose of improving the quality and value of clinical care and the health system. The first six obligations would be the responsibility of researchers, clinicians, health care systems administrators, payers, and purchasers. The seventh obligation would be borne by patients.

Authors of the feature articles are Nancy E. Kass, deputy director for public health in the Johns Hopkins Berman Institute of Bioethics; Ruth R. Faden, director of the Johns Hopkins Berman Institute of Bioethics; Steven N. Goodman, associate dean for clinical and translational research at the Stanford University School of Medicine; Peter Pronovost, director of the Armstrong Institute for Patient Safety and Quality at Johns Hopkins; Sean Tunis, founder, president, and chief executive officer of the Center for Medical Technology Policy in Baltimore; and Tom L. Beauchamp, a professor of philosophy at Georgetown University and a senior research scholar at the Kennedy Institute of Ethics. Beauchamp was a chief architect of the Belmont Report, which established the existing research ethics framework in the United States.

The commentaries on the articles find common cause with the need to update clinical oversight for learning health care systems, but offer important critiques of the proposed framework. In particular, some hold that the research-treatment distinction is still useful and are concerned that the obligation for patients to participate in quality improvement efforts would exempt too many studies from voluntary informed consent and IRB protections.

Reconsidering the Declaration of Helsinki

By Ezekiel J. Emanuel
The Lancet, Volume 381, Issue 9877, 
Pages 1532 - 1533, 4 May 2013
doi:10.1016/S0140-6736(13)60970-8

Next year will mark the 50th anniversary of the Declaration of Helsinki. Consequently, the World Medical Association (WMA) is developing its eighth version of the Declaration. This anniversary presents an excellent opportunity to reconsider the problems of the Declaration and how they can be remedied to ensure the document retains its prominent status.

In 1964 when the Declaration of Helsinki was initially enacted, it contained 11 articles and 713 words. At that time, the Declaration was unique. Over the years, ethical guidance on research involving human participants has proliferated substantially to encompass the Belmont Report by the US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research; the International Ethical Guidelines for Biomedical Research Involving Human Subjects of the Council for International Organizations of Medical Sciences; multiple laws and regulations, such as the US Federal Policy for the Protection of Human Subjects (known as the “Common Rule”, 45 CFR part 46) and the European Union's Clinical Trials Directive; and the eight principles of What Makes Research Ethical?. Simultaneously, the Declaration of Helsinki has been revised six times and tripled in size with its 35 articles and 2045 words. The revisions have often been extensive. For instance, the distinction between “clinical research combined with professional care” and “non-therapeutic clinical research” was eliminated after much withering criticism. The article that relates to use of placebos was revised and scaled back multiple times between 2000 and 2008.

Over the years problems with, and objections to, the document have accumulated. I propose that there are nine distinct problems with the current version of the Declaration of Helsinki: it has an incoherent structure; it confuses medical care and research; it addresses the wrong audience; it makes extraneous ethical provisions; it includes contradictions; it contains unnecessary repetitions; it uses multiple and poor phrasings; it includes excessive details; and it makes unjustified, unethical recommendations. For instance, the Declaration reads like a haphazard list of articles without an overall logical framework. The topics of articles 21 to 24 are literally a jumble: they cover the importance of the research outweighing research risks, the requirement for voluntary consent, the need to protect participants' privacy, and informed consent requirements for competent individuals, respectively.

The entire article is here.

Overhaul of Rules for Human Research Hits Impasse

By Paul Basken
The Chronicle of Higher Education
Originally published March 7, 2013

After months of trying to reconcile the sometimes competing goals of making the rules both simpler and tougher, while engaging 17 different federal agencies affected by the Common Rule, participants are describing the process as stalemated.

"I think it's dead, pretty much," said E. Greg Koski, a former director of the human-research-protections office, reflecting assessments he's heard from key players in the process.

The office has a published timetable suggesting it will formally propose a new set of regulations next month. In a written statement, the current director of the Office for Human Research Protections, Jerry A. Menikoff, said he intended to keep trying.

"This is, of course, a complicated undertaking, as was stated from the outset, and it takes time," Dr. Menikoff said.

The entire story, including The Chronicle's paywall, is here.

Ethics of 2 cancer studies questioned

India studies funded by Gates Foundation, National Cancer Institute draw scrutiny

By Bob Ortega
The Republic
Originally posted February 15, 2013

For more than 12 years, as part of two massive U.S-funded studies in India, researchers tracked a large group of women for cervical cancer but didn’t screen them, instead monitoring them as their cancers progressed. At least 79 of the women died.

One study, funded by the National Cancer Institute, did not adequately inform more than 76,000 women taking part about their alternatives for getting cervical-cancer screening; and those women did not give adequate informed consent, according to the Office of Human Research Protection, part of the U.S. Department of Health and Human Services.

The other study, funded by the Gates Foundation, is under review by the Food and Drug Administration, according to Kristina Borror, the OHRP’s director of compliance oversight. That study has raised similar concerns regarding 31,000 women who were tracked but not routinely screened or treated for cervical cancer.

Both studies continue today, though researchers for both told The Arizona Republic they have begun to offer screening to the women.

While the two studies differ in important respects, both included large numbers of women placed in “control groups” who were offered free visits with health-care workers, but who, until recently,were not screened for cervical cancer. Instead, researchers met with and tracked these women to monitor how many would develop cervical cancer and die, so their death rates could be compared with those of women who were being screened and treated for free.

The entire story is here.