Medical Research: An Ethical Breakdown / NYT Editorial

From today's NY Times on yet another medical research project (performed at 23 top academic medical centers) that was done sloppily, missing a standard-care arm, and failed to provide truly informed consent... performed on unconsenting very low birthweight newborns, who were at extremely high risk of a bad outcome, but who might also lead a normal life:

Despite reforms to protect patients from being harmed by medical research in recent decades, 23 academic institutions authorized a research project that failed to meet the most basic standard: providing an informed consent document to parents that accurately described the risks and benefits of the research to be conducted on extremely premature babies. 

This failure was startling, and deplorable. Federal officials have rightly demanded that the University of Alabama at Birmingham, the lead institution, and Stanford, Duke and Yale, among others, take corrective action to prevent a recurrence. Such actions, which must be approved by federal officials, could include requiring investigators to undergo additional training in the ethical conduct of research, enhancing oversight by institutional boards that monitor research and notifying parents of the ethical breach. 

The study involved more than 1,300 premature babies, born between 24 weeks and 27 weeks of gestation. The underdeveloped lungs in such babies are often unable to extract enough oxygen from the air to nourish the brain, so doctors often supply extra oxygen. 

The danger is that too much oxygen can cause severe eye damage and blindness, whereas too little can lead to brain damage and death. The current standard of care calls for the blood to be saturated with 85 percent to 95 percent oxygen, but the researchers sought to pinpoint a more exact range that would minimize eye damage without increasing the risk of death. 

The study, financed by the National Institutes of Health, was conducted between 2004 and 2009 and published in 2010. The researchers randomly divided the 1,300 babies into two groups; one got oxygen at the low end of the range, while the other got oxygen at the high end of the range. The parents were asked to sign consent forms that had been approved at all 23 medical centers by the institutional review boards that are supposed to ensure ethical conduct of federally supported research. 

But, in this case, the federal Office for Human Research Protections concluded that the consent forms failed to reveal that there was a greater risk of dying in the low-oxygen group and a greater risk of severe eye damage in the high oxygen group. The form also stated that, because both groups would receive oxygen within the standard of care, there would be no predictable increase in risk no matter which group a baby was in. 

But the federal agency found that many infants could have faced greater risks by participating. For example, if a baby whose clinical needs might ordinarily have led doctors to deliver a relatively high level of oxygen was enrolled in the study, the infant might be randomly assigned to receive lower levels of oxygen. The Department of Health and Human Services needs to investigate how this breakdown occurred. And if the institutions do not offer strong reforms, the agency can suspend their ability to conduct federally financed research on human subjects.

Rights Groups, in Letter to Obama, Question Legality and Secrecy of Drone Killings/ NYT

Finally, human rights advocates are asking the US government on what legal basis it can choose to assassinate people, and by the way, what is the process for choosing who gets offed and another thing, what's up with the drones?!  The usual administration response is just too precious: “Our approach is marked by scrupulous adherence to the rule of law.”

Scott Shane of the NYT reports on a letter sent by NGOs and some at the NYU and Columbia law schools:

In a letter sent to President Obama this week, the nation’s leading human rights organizations questioned the legal basis for targeted killing and called for an end to the secrecy surrounding the use of drones.The “statement of shared concern” said the administration should “publicly disclose key targeted killing standards and criteria; ensure that U.S. lethal force operations abroad comply with international law; enable meaningful Congressional oversight and judicial review; and ensure effective investigations, tracking and response to civilian harm.”The nine-page letter, signed by the American Civil Liberties Union, Amnesty International, the Center for Constitutional Rights, Human Rights First, Human Rights Watch, the Open Society Foundations and several other groups, is the most significant critique to date by advocacy groups of what has become the centerpiece of the United States’ counterterrorism efforts.While not directly calling the strikes illegal under international law, the letter lists what it calls troubling reports of the criteria used by the Central Intelligence Agency and the Pentagon’s Joint Special Operations Command to select targets and assess results. The reported policies raise “serious questions about whether the U.S. is operating in accordance with international law,” the letter says. It is also signed by the Center for Civilians in Conflict and units of the New York University and Columbia Law Schools.The letter comes as American strikes in Pakistan, Yemen and Somalia, and the example the United States has set for the world, are drawing intense scrutiny. United Nations human rights investigators are reviewing the American record, and Congress has shown a new willingness to discuss the classified program in public, with a House subcommittee hearing on the constitutional and counterterrorism implications of targeted killing set for April 23. That hearing was postponed for a week in an effort to persuade the administration to send an official to testify, a committee aide said.Caitlin Hayden, a spokeswoman for the National Security Council, said the administration was “committed to institutionalizing and explaining to the Congress and the public as much as possible about our drone policies, including the process for making strike decisions.” She added: “Our approach is marked by scrupulous adherence to the rule of law.”By the count of the New America Foundation, a research group that tries to track targeted killing, the United States has carried out 422 strikes in Pakistan and Yemen, 373 of them since Mr. Obama took office in 2009, in addition to a handful in Somalia. The foundation estimates the number of deaths resulting from the strikes to be between 2,426 and 3,969, of which about 10 percent were of civilians and nearly as many of which were identified as “unknown.” An overwhelming majority of the strikes have been carried out by unmanned drone aircraft, though cruise missiles, fighter jets and helicopter gunships have also been used.Agreeing to the degree of openness sought by the human rights groups would mean a sea change for the Obama administration. Though officials have given a series of careful speeches on the administration’s legal reasoning, the Justice Department’s classified legal opinions on the subject have been shared only recently, even with the Senate and House Intelligence Committees, and the government has asserted in battling Freedom of Information Act lawsuits that the Pakistan strikes are too politically delicate even to be officially acknowledged.Gabor Rona, the international legal director of Human Rights First, said that the letter to Mr. Obama reflected increasing concern that government secrecy has hidden grave legal and practical problems with the strikes.“The more the administration is rightly forced to disclose about who it is killing and why,” he said, “the more obvious it becomes that the practice is growing, is illegal in its scope, is causing large-scale civilian casualties and is a slow-moving train wreck with serious blowback consequences to U.S. national security.”In pushing for greater candor, both the human rights groups and Congress are responding to Mr. Obama’s own stated goal. In his State of the Union address in January, the president said: “In our democracy, no one should just take my word that we’re doing things the right way. So, in the months ahead, I will continue to engage with Congress to ensure not only that our targeting, detention and prosecution of terrorists remains consistent with our laws and system of checks and balances, but that our efforts are even more transparent to the American people and to the world.”No action has followed so far. In announcing his plans for a Judiciary Committee hearing, Senator Richard J. Durbin, the Senate’s second-ranking Democrat, noted that Mr. Obama “has made it clear he wants to work with Congress to establish ‘a legal architecture’ for drone strikes to prevent abuses.” Mr. Durbin said the hearing would “begin this important constitutional debate.”The Obama administration has been asked to provide a witness to discuss its position on the drone strikes, but the administration has so far not agreed to provide one, according to the committee’s staff. Similarly, efforts on Thursday by Representative Jan Schakowsky, Democrat of Illinois, to get John O. Brennan, formerly the president’s counterterrorism adviser and now the C.I.A. director, to discuss strike policies during a hearing of the House Intelligence Committee went nowhere.“I would say right now that I am at the helm of the C.I.A. and will carry out policy guidance as directed by the administration,” Mr. Brennan said.Ms. Schakowsky was prompted to question Mr. Brennan in part by an article this week by McClatchy News Service reporting that it had obtained classified government documents showing that the drone strikes had killed hundreds of low-level suspected militants whose identities were not known. The article suggested that the documents undercut assertions by Mr. Obama and his aides.“There are a lot of things that are printed in the press that are inaccurate, in my mind, and misrepresent the facts,” Mr. Brennan said. When Ms. Schakowsky pressed the point, he said, “I’m not going to engage in any type of discussion on that here today, congresswoman."

Association between Guillain-Barré syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis/ Lancet

A US government-Harvard-Hopkins study confirmed what was obvious from many prior, similar studies:  flu shots cause occasional cases of paralytic Guillain Barre Syndrome, with or without adjuvants.  In this case, about 1.6 additional GBS cases per million vaccinations, or approximately double the baseline risk in the six weeks following the vaccination.  From the Lancet:

Dr Daniel A Salmon PhD a c , Michael Proschan PhD d, Richard Forshee PhD e, Paul Gargiullo PhD f, William Bleser MSPH a,Dale R Burwen MD e, Francesca Cunningham PharmD g, Patrick Garman PhD h, Sharon K Greene PhD i, Grace M Lee MD i, Claudia Vellozzi MD f, W Katherine Yih PhD i, Bruce Gellin MD a, Nicole Lurie MD b, the H1N1 GBS Meta-Analysis Working Group†

The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barré syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barré syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barré syndrome.MethodsData were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barré syndrome per million vaccinations. We used a self-controlled risk-interval design.FindingsInfluenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barré syndrome (incidence rate ratio 2·35, 95% CI 1·42—4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barré syndrome per million people vaccinated.InterpretationThe modest risk of Guillain-Barré syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks.FundingUS Federal Government.