Closing the Gap Now — the conference

I’m at a remarkable conference at the University of Minnesota, Kudos to John Morrissey for bringing this group together, and thank you, John, for inviting me to speak.

The conference challenges the conventional wisdom that new cancer drugs that show promise in Phase 1 trials must be further evaluated through large phase 2 and 3 studies.

One problem in finding innovative approaches to cancer is the inertia of federal regulatory agencies, including FDA and OHRP. Their circumstances are not quite the same, however.

FDA is solidly entrenched and widely known as the agency that will have control over what new drugs, devices, and biologics can be marketed. We hope that FDA will become more open to new ways of demonstrating therapeutic effectiveness apart from classic randomized controlled trials.

OHRP is in a more tenuous situation. Its name is unknown outside the research community. We know today that the regulatory approach of OHRP, and the IRB process that it oversees, has failed. The sooner everyone involved realizes this, the better.

This audio is of the 13 minute talk I gave on the problems with regulation under OHRP and the possible solutions. It’s a live recording, please forgive the occasional rattle of silverware and coffee cups.

I mention Brittany Madden, the young woman, suffering from incurable brain cancer, who moved to Oregon in order to be able to get medical help in hastening her death at the time she chose. It’s a heartbreaking story. We should be doing more to find answers to brain cancer and other serious diseases, and less to regulate (and slow) the scientists who can find those answers.



Your IRB Service

This is taken from a forthcoming manual for IRB members.

You should take pride in your work on the IRB, but pride should not be your only reward. You should serve on fair terms and, in particular, you should be fairly compensated and adequately protected. [Read more…]

Protecting the Scientist from her Subjects

You are a young British woman living in the United States, studying what happens to prisoners after they are released on parole. You come to know many of these men as they try to adapt to their new lives; they are free at last, but free to do what? They face many challenges.

Ruth Armstrong

They are not criminological stick figures. They are real men, who tell you candidly the challenges they face.

And they challenge you. You cannot be a detached, objective observer and still deserve their trust. Through your conversations with them, you understand their lives, their hopes and their failures. [Read more…]

European Privacy Legislation Threatens Research

Thoughtless privacy protection threatens vital research. This problem is now in the news in Europe, although it’s a problem all over the developed world. The European Parliament is considering two amendments that would make it impossible to conduct vital health research.

When medical records were kept on paper, privacy protection meant keeping an unauthorized person from flipping through your file. Now that medical records are (mostly) electronic, privacy protection can still mean excluding unauthorized persons. But when it excludes qualified researchers, it is likely to do more harm than good.

We need to rethink our concepts of what privacy means and how it must be protected. [Read more…]

Ethics and Regulation

This is part of a forthcoming manual for IRB members.

Your IRB performs a regulatory function with an ethical purpose.


Your IRB balances two ethical goals: improving our collective welfare and protecting individual research subjects. Hans Jonas, a philosopher, has examined these goals, praising the value of research in promoting “health and, in its more critical aspect, life itself,” which are “clearly superlative goals.” Society benefits from “active and constant improvement in…the waging of the war against nature. This is an expansive goal” with “the nobility of the free, forward thrust. It surely is worth sacrifices.”1

But, Jonas continues, this ethical goal cannot be pursued by unethical means. Society cannot conscript the unwilling individual to serve as an experimental subject, no matter how important the knowledge to be gained. To do so would be to abandon “the moral basis on which society’s existence rests.”1 Henry Beecher, another early ethicist, put it more bluntly: “Whoever gave the investigator the god-like right of choosing martyrs?”2 [Read more…]

The Goals of Consent

This is taken from a forthcoming manual for IRB members.

Consent is intended to serve both subjects and scientists. Consent makes some research that is risky possible. A scientist has no right to conduct biomedical research with any measurable risk unless the subject consents. That same research is made ethical by the participation of willing subjects.

Consent also serves subjects in many ways. Consent puts subjects on notice that they are in an experiment of some kind. It provides potential subjects with information they may use to make a decision about participation. It informs them of what to expect if they enter the study. Preparing a consent form is also a reality check for the investigator: is it reasonable to expect people to participate in this research? Consent thus acts on both the scientist and the subject. [Read more…]

IRB Control of Subject Payment

This is taken from a forthcoming manual for IRB members.

The NIH’s original IRB, the Clinical Research Committee, was not troubled that some of the Clinical Center’s subjects were paid. The 1966 guidelines that established the IRB system did not mention subject payment, nor do the regulations that OHRP administers today.

This is appropriate. In ordinary circumstances, an IRB will have nothing to contribute to the issue of subject payment. [Read more…]

IRBs and the Literature Search

This is taken from a forthcoming manual for IRB members.

Your IRB will be at a disadvantage in understanding any given protocol compared with scientists who have made this specific niche their life’s work. Some commentators see a thorough review of the literature as a vital tool to bring the IRB to near parity with the investigator. This literature review could be done by the investigator or the IRB itself. Let’s consider first whether your IRB should conduct its own literature review.

I support your putting in the time to attain a reasonable understanding of the science you review. There is no reason to restrict yourself to the information provided in the protocol, and there would be no harm in conducting your own literature search, but it will rarely be necessary. In most institutions, IRB members with questions are encouraged to contact the investigator directly, and you can always query outside experts. A review of the literature can be useful on a case by case basis, but I am not aware of any IRB that routinely reviews the literature for all, or even most, of the protocols it reviews. [Read more…]

(Genetic) Information is Safe

Barbara Evans is doubtless the only First Amendment scholar with a degree in electrical engineering, so when she writes about the uproar that William Tyndale’s Bible caused in 1525, then links that controversy to the return of genetic information to research subjects in 2014, the chances are good that she’s up to something interesting.

Barbara Evans

Barbara Evans

Evans’s article, “The First Amendment Right to Speak about the Human Genome,” is fascinating; you can access it without charge at I’m not going to diminish the astonishing connections Evans makes by summarizing them here. Go to the article itself.

She and I have been corresponding about the issues involved, and she wrote:

I want to convey the message that respecting First Amendment rights is the SAFE thing for IRBs and institutions to do. ”Facts are Friendly,” even if they sometimes make people upset or uncomfortable, and even if an honest disclosure needs to make clear that the facts are still very much up in the air. I’m not saying to foist information on unwilling listeners or to force investigators to spill information they do not want to disclose. But if a research subject asks for information and an investigator is willing to provide it, IRBs and regulators should not get in the way of consensual communication.

A segment of the bioethics community seems convinced that information is dangerous and that IRBs need to protect the world from it. Information is not dangerous. Facts are safe.  If people do crazy things in response to that information, then we need to intercede to get them not to do those silly things. But we should not block the flow of information.  People are better off knowing facts than not knowing them.  That’s the point of the First Amendment. I don’t agree that information is dangerous.  It’s just information.

Evans’s message is having an impact. Rod Smolla, the distinguished Constitutional scholar, is including her essay in the next edition of The First Amendment Law Handbook, published by West, a yearly compendium of notable First Amendment law review articles. Look for it in the Fall.


Controversy in the Social Sciences

This is taken from a forthcoming manual for IRB members.

The IRB should remember that research in controversial topics is a hallmark of a vigorous university and do all it can to support it.

Every IRB must have a member who is not affiliated with the institution, who is typically referred to as the “community member.” The community member needs to be particularly cognizant of the value of controversy promoting a healthy society; otherwise the conventional wisdom and political correctness, repackaged as community values, will suppress important research.

Another View: Never Give Offense

Whalen and Khin-Maung-Gyi see the community member as representative of community sensibilities. They write that “the voice of the IRB is a social and cultural one and not exclusively one of technical (scientific, public policy, legal, public relations, political, or economic) expertise.”1 In this view, the IRB is justified in forbidding research that is socially or culturally offensive to the community member. [Read more…]

Consent in Social Science Research

This is taken from a forthcoming manual for IRB members.

The social sciences have their own traditions of how subjects consent to participate in research. Sometimes consent is omitted because the scientist intends to expose the subject’s illegal or immoral conduct. This does not fit well with the biomedical paradigm, but it is appropriate when the subjects are corrupt politicians, brutal police officers, or members of the Ku Klux Klan.

In another section, I said that your goal remains “to protect the rights and welfare of innocent subjects.” The word “innocent” is important. The IRB should feel no duty to protect the corrupt, the brutal, and the racist from exposure.

The regulations were written with biomedical subjects, not Klan members, in mind, so they provide no exception for the work of anthropologists or sociologists. Instead, the regulations state flatly that “no investigator may involve a human being as a … unless the investigator has obtained the legally effective informed consent of the subject …”1 There is no exception for cases in which the scientist is investigating antisocial or criminal conduct. This wording, taken literally, means that a sociologist who loathes the Ku Klux Klan and wants to attend a meeting must first obtain the informed consent of the local Wizard. [Read more…]

Ethics Boards and Risk in Social Science Research

This is taken from a forthcoming manual for IRB members.

Although the regulations were drafted with biomedical research in mind, most or all American universities require IRB oversight of research in the social sciences, including sociology, anthropology, economics, and political science; many extend IRB responsibilities to other fields, including history, the humanities, journalism, and empirical legal studies. Thoughtless application of the regulations outside of biomedicine can produce results that are ridiculous or flat wrong.

Your IRB must find a way to apply inapplicable rules and reach a sensible regulatory result.

Officials at OHRP have provided no systematic help. In fact, as Zachary Schrag has shown in his shocking Ethical imperialism: Institutional review boards and the social sciences, 1965-2009,1 federal officials, since the creation of OPRR, have put more effort into extending the system’s dominion over history and the social sciences than attempting to govern them sensibly.

In the absence of thoughtful federal guidance, you’re on your own. You cannot even find a consensus within the social scientists as to what constitutes ethical research practices. The American Sociological Association, for instance, has a code of ethics that some sociologists detest because they believe it privileges civility over inquiry.

My own conviction is that everyone benefits when social scientist are free to ask awkward questions as they explore how society works. Here as elsewhere, IRBs function best when they focus on serious threats to the rights and welfare of innocent subjects, bearing in mind that the word “subjects” is often inapposite in this work. [Read more…]

Academic Freedom

 This is taken from a forthcoming manual for IRB members.

You are in a privileged position. If your IRB reviews research in psychology, the social sciences, or other fields like English and journalism, you will be at a ringside seat as scientists and scholars in a multitude of academic niches struggle to better understand our world, to train the young scholars that will follow them, and to debate each other—sometimes politely, sometimes with venom.

James Shannon of the NIH specifically intended IRBs to review PHS-funded research in the social sciences,1 and the National Research Act of 1974 requires IRB review of “biomedical and behavioral” research. Lest IRBs use their position of power to pursue political ends, the regulations specifically state, “The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.”2

So, for instance, an IRB member may be personally in favor of affirmative action, but he or she is prohibited from blocking research intended to show that affirmative action programs fail. The IRB should evaluate research like this in terms of its safety for subjects, not its impact on society.

Controversy is Valuable

Your IRB has a duty to protect research subjects’ rights and welfare. As a member of the university (or another learning institution), you also have an obligation not to meddle with research that seems misguided or offensive, so long as its subjects are not placed in jeopardy. The university should be at the vanguard in discussions of issues that are important to society, including such sensitive issues as racial and gender discrimination and the treatment of military detainees. Your IRB should interfere in this tumultuous but vital discourse only when there is clear evidence of risk to subjects that cannot be mitigated through an appropriate consent process.

During the student protests of the 1960s, the University of Chicago asked a group of senior faculty to report on “the University’s role in political and social action.” Law Professor Harry Kalven, Jr., chaired the group, and the report included this memorable statement: “The mission of the university is the discovery, improvement, and dissemination of knowledge. Its domain of inquiry and scrutiny includes all aspects and all values of society. A university faithful to its mission will provide enduring challenges to social values, policies, practices, and institutions. By design and by effect, it is the institution which creates discontent with the existing social arrangements and proposes new ones. In brief, a good university, like Socrates, will be upsetting.”3

Another Viewpoint: The University’s Reputation Must be Protected

Jonathan Moss, Professor of Anesthesiology and Critical Care and Chair of the IRB for biological sciences at the University of Chicago, rejects this point of view and sees the IRB as an important tool in protecting the university’s interests. IRBs, he writes, “can forestall the public image problems and protect the institution’s reputation by weeding out politically sensitive studies before they are approved.”4

No one has surveyed IRB members to see how they feel about controversial research, but I hope that few agree with Moss that they should suppress research on political grounds. Yet Stephen Ceci and his coauthors demonstrated politically-motivated review in a troubling study in 1985, thus showing that fear of controversy far antedates Moss’s 2007 comments.

Stephen Ceci

Stephen Ceci

[Read more…]

IRB Censorship

This is taken from a forthcoming manual for IRB members.

When you serve on the IRB, you are likely to review controversial research (for instance, studies of sexual behavior or racial discrimination). This raises the important and complex question of censorship.

IRBs at times, most unfortunately, disapprove research simply because the topic is politically sensitive. This is not only an affront to academic freedom. It is an act of censorship, for the First Amendment protects our right to ask questions of people and publish what we learn. IRBs act like this with the best of intentions—to protect the university from controversy or to block ideologically reprehensible research. Good intentions, however, are not enough.

In 1979, the great political scientist Ithiel de Sola Pool attacked IRB regulations that “require prior review (i.e. censorship) of much research that is to be conducted by interviews and other forms of speech.” Pool noted the First Amendment’s prohibition of prior restraint of speech and concluded, “Beyond doubt, any attempt by DHEW to require researchers to get permission from a review board before they engage in conversation (i.e. speech) with a human subject is unconstitutional.”1

Philip Hamburger

Philip Hamburger

Pool’s argument has recently been expanded by Philip Hamburger, a distinguished professor at Columbia Law School. Hamburger agrees that IRBs can regulate the behavior of some biomedical researchers. But it is a violation of the Constitution when an IRB regulates “inquiry, recording, talking, writing, and publishing.” Licensing—a system in which people were forbidden to publish without a license from the government—was characteristic of early English systems of censorship, and Hamburger sees the IRB system as a replica of that reviled model. As he writes, “The federal government imposes a system of licensing, and research institutions and their IRBs carry it out.”2 [Read more…]

Governing Research at Alder Hey Children’s Hospital

A sick child’s fear is dangerous. A frightened child cannot answer questions or relax enough to permit an optimal physical exam. Consider a typical scenario, one that is played out over and over in emergency departments around the world, including the busy service at internationally-recognized Alder Hey Children’s Hospital in Liverpool.

In this discussion, Alder Hey illustrates both the creative and valuable role research plays in modern medicine, and how an antiquated system of ethics review could, and should, be replaced by a rational model.

Image courtesy of Shutterstock

Image courtesy of Shutterstock

We’ll assume the little boy (we’ll call him Aidan) was brought in, feverish and irritable, by his grandmother. Aidan lies on the gurney in room 4, his face flushed. His grandmother, seated next to him, holds his hand.

A Challenging Exam

A man in a white coat enters; we will call him Dr. H. He speaks quietly with Aidan’s grandmother, then turns to the boy and explains he is going to check him to see what is wrong. Aidan begins crying as Dr. H’s soft hands press on his belly, under his arms, then bend and straighten his limbs, one at a time. [Read more…]

The Ethics Hammer

In 2003 I surveyed federally-funded scientists about their experience—good, bad, or indifferent—with IRBs. I was surprised when one said that because “our emails may be monitored” it might be unwise to conduct the survey by email. Another respondent spoke from experience about board members with an agenda: “There is…quite some show of ‘muscle’ and if a member has a score to settle with an investigator, woe to the whole study.”1

Their observations are supported by published evidence. The University of North Carolina used its IRB to help silence Mary Willingham, the education specialist who exposed the system through which some Tar Heel athletes are cheated of a college education.2 As Stewart Baker commented on the Volokh Conspiracy, “what handier weapon to use against inconvenient speech” than the ethics regulations?

The Montreal Neurological Institute used its ethics board as part of a campaign against neuropsychologist Justine Sergent. Sergent apparently did not know that the only survival method when the ethics board reprimands you is to assume a posture of abject humility. Instead, she fought back, which egged the institution on; this struggle ended only with her suicide.3


Will van den Hoonaard

Will van den Hoonaard, in his excellent if frightening Seduction of Ethics, documents research ethics boards (REBs) that conduct vendettas against disfavored investigators. You don’t even have to be deficient in humility; you can simply be too successful. One example “involves an REB’s desire to create obstacles for a very promising, relatively young and highly acclaimed researcher. Members of the REB were jealous of that researcher’s accomplishments.”4 [Read more…]

A New IRB Manual: The System’s Creation and Triumph

The IRB manual is under revision. I’ll put a note on twitter when I have a new version ready to post (@Suff_Science).

How Cancer Research Should Be Governed

The procedure room smells of disinfectant. The man in the white coat, sitting on a stool, keeps up a reassuring patter as he swabs the skin of the old man. “I am Dr. Southam,” he says. “I’m going to clean a spot on your leg with some alcohol.”

Chester Southam

Chester Southam

Southam takes a small syringe from the stand. “This is Novocain, it doesn’t hurt, you’ve had it before.”

There is no suggestion that this unfamiliar procedure is not part of the patient’s routine care. If the man demands to know what is being done, Southam has a ready explanation. “I’m going to inject some cells to test your immune system.” Southam takes a second syringe from the tray and deftly injects a small amount of cloudy fluid just under the skin.

The year was 1963; the cloudy fluid contained live cancer cells. 1

Scandal at the Jewish Chronic Disease Hospital

[Read more…]

Suffocating Science Harms Everyone

Research ethics boards block scientists and scholars from doing important research, wielding their power in universities and hospitals from Perth to Liverpool to San Francisco. They may be called ethics committees (in Australia, the United Kingdom, and Canada) or institutional review boards/IRBs (in the United States). Under any name, their malign effects are the same.

They may be called research ethics committees, but don’t let the word “ethics” deceive you: They are regulators. The people who staff them are honest, hard-working, and well-meaning, but the system has acquired a malignant life of its own, one that focuses on the rules and disregards anything that gets in the way. It harms science and scholarship by slowing and damaging research. Hundreds of articles in the professional literature tell this story; it is time to move the discussion into the public arena.

The Suppression of Inquiry

In theory, their remit is to protect research subjects. But they have moved far beyond that limited goal and now suppress the rights of scientists to find better treatments for diseases and of scholars to study individuals and society. Because I am a professor, I must obtain permission from an ethics board before I can talk with people and publish what I learn, just as my colleagues must ask permission before they can do research in child abuse or Alzheimer’s disease.

Philip Hamburger

Philip Hamburger

Philip Hamburger, a distinguished scholar at Columbia Law School in New York, has written two superb essays about the unconstitutionality of the system. If you are interested in how this government-required system strips scholars of their rights to speech and inquiry, his essay Getting Permission is fascinating—and shocking. [Read more…]

Influenza Research Gridlock in the UK and the US

Ian Sample, science correspondent for the Guardian, reports that the regulation of research in the United Kingdom is still stuck hard in bureaucratic mud in Thousands of lives put at risk by clinical trials system that is ‘not fit for purpose’.

Ian Sample

Ian Sample

The 2009 Influenza Pandemic-and-Debacle

For background, Sample takes us back to the 2009 influenza pandemic, when Peter Openshaw, a specialist in lung disease, planned a study to determine why some people infected by the virus lived when others died—clearly useful information to have.

Peter Openshaw

Peter Openshaw

The pandemic began in April; Openshaw hoped to begin recruiting subjects in May. But obtaining the required approvals was so cumbersome that he did not enroll his first patient until December, when the first wave of the pandemic was already waning.

Ethics review was only part of the problem. Openshaw told Sample that he not only had to obtain a legal agreement with every one of the 11 hospitals involved, but that some of the hospitals wanted separate contracts with all the other hospitals.

What a nightmare! So how are things now?

Things Haven’t Gotten Much Better

Jeremy Farrar, head of the Wellcome Trust and an expert on infectious diseases, says that the system puts “public health at risk” because research governance systems “are not fit for purpose when the situation is moving quickly.” As a result, it is “impossible to run crucial tests in good time.” [Read more…]

Research Ethics Review—A Failed System of Risk Management.
Part 1: Overcome by Risk

Research ethics boards serve a risk management function, but they do so using an archaic approach to risk management that has long been discarded in management theory. This outdated method predictably leads to their failure to reach appropriate judgments across a broad array of research disciplines.

Despite minor differences from country to country, the fundamental problems are the same around the globe. Ethics board decisions lack balance because boards focus on the risks of research without giving due weight to other considerations such as benefit to society. Further, they function without the oversight that would otherwise give them a chance to correct their unbalanced review. [Read more…]