Note: The following article concerns a 2006 guidance from the FDA, which purported to affect the way preclinical drug testing is carried out. As noted, I am interested in this subject, and I'd like to do so more work on it, regarding, for example, how this matter is affected by the notice of proposed rulemaking concerning the federal Common Rule concerning human subjects research.

Given recent developments, I am not sure I will post this on the Social Sciences Research Network (SSRN). However, I am not entirely satisfied with the way the footnotes are produced on this blogger website. If any scholars have suggestions, I'd be gratified to hear from you. My email address is on the blog.

Phase 0 Trials: A Fait Accompli?

A Reappraisal From a Ten-Year Perspective (1)

by John Otrompke, JD(*)

In 2006, the FDA released a guidance on Phase 0 trials, in which a ‘microdose’ ( less than 1% of the expected dose) of an experimental drug is administered to humans for a very brief period of time (perhaps one week).2

The guidance generated controversy, such as an article raising ethical questions like whether it is ethical to subject humans to the risk of taking a new drug, which has been subjected to less rigorous preclinical research than in a traditional Phase 1 trial, without offering the possibility of enjoying a therapeutic benefit.3

Today, Phase 0 trials occur frequently, without substantive comment.4 In fact, the entire proposal in advance of amending the U.S. Common Rule doesn’t even mention them.5 So ten years out, are Phase 0 trials a fait accompli?

It would seem so. When Prof. Kimmelman wrote his article, his review of the literature found no more than 10 such studies. Perhaps for this reason, the 2007 article raised, but did not attempt to answer, such ethical questions.

But a similar search conducted on PubMed last month returned 1,892 hits for Phase 0 trials, and 544 hits for microdosing; a search on clinicaltrials.gov returned 97 studies. Regulators in Australia(6) and the European Union(7) have given Phase 0 trials their blessing.

Have the ethical issues raised by Prof. Kimmelman ever been addressed? At least one of the ethical questions he raised, whether Phase 0 trials have scientific value, seems to have been answered, at least to the satisfaction of society and the scientific community. 

Another issue, however, has never been sufficiently addressed: whether society is permitting human volunteers to subject themselves to an unquantifiable but substantial risk, to which they cannot truly consent. 

This article takes the position that Phase 0 trials are part of a next-generation tool-box for drug discovery (including genomic browsers, micro-fluidics, biomarkers, gene signatures and other modern techniques) that may one day eliminate animal testing,(8) and cure cancer. While the practice of Phase 0 trials is only likely to accelerate given the administration’s National Cancer Moonshot initiative, the federal government should take the opportunity presented by the proposal to amend the Common Rule(9) to produce a more definitive response to the ethical issues they raise.

What are Phase 0 Trials?

In its 2006 guidance, FDA defines the concept of microdose trials, and lays out how to use them.

In traditional, pre-2006 drug development, clinical trial research was broken down into three phases, preceded by basic, in vitro research, proof-of-concept, and animal testing; Phase 1, in which doses of a medicine were administered to human beings for titration and to further test for safety; Phase 2, in which the experimental medicine is given to larger numbers of patients, to further test for safety as well as efficacy; and Phase 3, the most complete and scientifically rigorous phase, in which the medicine is administered to a cohort large enough to generate statistically significant results, the primary endpoint being efficacy. 

In order to conduct a Phase 1 trial, a drug developer needs to submit an application to FDA. In its guidance, FDA explained that many drug developers submitted vastly more data than necessary to get approval for Phase 1 trials, unnecessarily constricting scientific progress and hindering medical progress.10 

The FDA explained just how little scientific evidence is necessary to justify a Phase 1 trial, and encouraging drug developers to rely on a hitherto under-utilized technique called the Phase 0, or microdose trial. The point was to simplify the process by sorting out the more promising agents by trying them out earlier in humans in a microdose form.

While traditional Phase 1 trials had once been referred to as ‘first-in-human’ studies, with Phase 0 research, this is no longer the case. 

What Ethical Issues Have Been Raised?

What exactly is the ethical difference between Phase 0 and Phase 1? Chiefly, while the likelihood of a human subject receiving a therapeutic benefit from a Phase 1 trial is small, the odds of receiving any therapeutic benefit from a Phase 0 trial are virtually nil, partially because the dose of the experimental drug is so small, and the period of administration is so brief.11

Stepping back, the U.S. government’s three basic watchwords for bioethical regulation may be found in the Belmont Report, the document which informed the creation of the Common Rule: respect for persons, beneficence, and justice. 

Many of the criticisms leveled at Phase 0 trials come from the proposition that risks and benefits faced by human subjects must be proportional. (Prof. Kimmelman expressly excluded consideration of research in healthy people from his consideration, but the FDA guidance said that exploratory studies could be conducted in healthy individuals).12 Unlike in traditional Phase 1 trials, the dose of the experimental agent in a Phase 0 trial is very small. Therein lies the rub. 

First-in-human studies of experimental medicines can pose grave health hazards. The Guidance addresses such concerns by encouraging animal testing in a rather unrestrained way, notwithstanding the burgeoning evidence that animal research does not produce results reliably generalizable to human beings.13 (At the same time, federal agencies are doing significant work in developing alternatives to animal testing through programs like ICCVAM and NICEATM, programs in which FDA is involved, but in which FDA should place greater confidence).14

Therefore, a human individual taking part in a Phase 0 trial often assumes a significant risk, without much likelihood of enjoying a personal medical benefit. An adult might assume a risk to herself or himself for the benefit of others.15 It is assumed that this can be ethically permissible, if the benefit to others is sufficient. But experimental drugs are tested in humans earlier than was the case in traditional Phase I studies, which involved a more rigorous period of preclinical study. Prof. Kimmelman asks us whether the public benefit is sufficient to justify greater individual risk if Phase 0 trials are unlikely to lead to generalizable scientific knowledge, because, for example, the results of Phase 0 trials may never be publicly available. Is it just if human beings are exposed to danger, not to develop generalized knowledge, but to advance the individual development of a privately-owned drug that will ultimately be sold for profit, sometimes at objectionable rates? Is it possible for an individual to consent in a truly autonomous way to willingly participate in such an unequivocally unilateral procedure, and why would they do so?

To really answer these questions, it would be necessary to quantify the risk to which those who volunteer for Phase 0 trials are subjecting themselves. Are human volunteers experiencing more adverse events than before? Are any Phase 0 volunteers enjoying pharmacological benefit? 

Bioethicists have commented that this is a difficult calculation, because it is difficult to keep track of adverse events encountered by volunteers in clinical trials. These concerns may have been partially alleviated by the expansion of the ClinicalTrials.gov database, which was expanded again this month.16 According to the agencies, the database can be searched for adverse events.

Ten years on, federal regulators and the not-infallible scientific community seem to have concluded that Phase 0 trials present enough promise to justify the individual risk to human volunteers. (Concerns that the benefit is private could perhaps be better addressed by efforts to reform the phenomena of commerce more generally). 

It may be that the outcome of the Cancer Moonshot Initiative will ultimately determine whether the sacrifices made by individual human beings were worthwhile.

Conclusion

Some say that the focus of bioethical regulation in the U.S. has shifted from informed consent to an emphasis on access to experimental medicine. In light of the observations and conclusions contained above, Phase 0 trials are indeed a fait accompli, for the time being at least; but because the history of medical ethics in the last century has been reactive in nature, that could change.

Probably the most important document of research ethics since the turn of the century is the notice of proposed rulemaking to amend the Common Rule.17 The NPR doesn’t explicitly mention Phase 0 trials, but several aspects of its language may bear on some of the ethical concerns discussed above.

Therefore, a subsequent article could explore how that language ameliorates or aggravates the concerns mentioned above.

* John Otrompke, JD, is a bioethicist and medical journalist. A graduate of DePaul University College of Law, with a certificate in health and hospital law, he was a 2015 faculty recruitment applicant at the Association of American Law Schools. He has never been engaged in the practice of law. He blogs at www.otrompkescommentaries.blogspot.com. He can be reached via email at John_Otrompke@yahoo.com

Notes

1. The author wishes to thank Prof. Barbara Evans, JD, PhD, of the University of Houston Law Center, and Prof. Seema Shah, JD, association professor at the Truman Katz Center for Bioethics at the University of Washington for their many helpful comments. Any errors are my own.

2 Guidance for Industry, Investigators, and Reviewers: Exploratory IND Studies (January 2006).

3 “Ethics at Phase O Clarifying the Issues,” J. Kimmelman, 35 J.L. Med. & Ethics 727 (2007). Prof. Kimmelman raised, but did not answer a number of such ethical questions. See also, “Phase 0 trials: a platform for drug development?”, editorial, The Lancet (July18, 2009), p. 176.

4 For exceptions, see: “Note: The FDA Clinical Trial Process: Effectuating Change in the Regulatory Framework Governing Clinical Trials to Account for the Historical Shift from ‘Traditional’ to ‘New’ Phase I Trials,” J. Aldest, 18 Health Matrix 463 (2008), pp. 474-477; “First-in-Human Trial Participants: Not a Vulnerable Population, but Vulnerable Nonetheless,” R. Dresser, 37 J.L. Med. & Ethics 38 (2009), p. 39 et seq; “Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field,” L. Fatehi, 40 J.L. Med. & Ethics 716 (2012), p. 732-735; “Revising the Regulation of Stem Cell-Based Therapies: Critical Assessment of Potential Models,” B. Von Tigerstrom,  70 Food & Drug L.J. 315 (2015), p. 330.

5 Federal Register, Notice of Proposed Rulemaking, p 539334 (September 8, 2015)

6 “Regulatory Challenges of Synthetic Biology Trials and Other Highly Innovative Investigational Products,” L. Eckstein,  15 Macquarie L.J. 65 (2015), n.12.

7 “Position Paper on Non-Clinical Safety Studies to Support Clinical Trials with a Single Microdose,” EMEA Committee for Proprietary Medicinal Products (23 January 2003).

8 "Early Microdose Drug Studies in Human Volunteers Can Minimise Animal Testing: Proceedings of a Workshop Organised by Volunteers in Research and Testing.” Combes R, et al. 19 Euro J Pharma Sciences 1, pp 1-11 (2003).

9 See, for example, “Significant Changes to Institutional Review Boards Proposed,” J. Otrompke, IEEE’s Pulse Magazine, November-December 2012.

10 Guidance, supra n. 1 (p. 2, n. 4).

11 However, the guidance assumed that some exploratory studies might theoretically “induce pharmacologic effects.” Guidance, supra n.1 (p. 9).

12 Guidance, supra n.1 (p. 5).

13 Animal Research in Medical Sciences: Seeking a Convergence of Science, Medicine, and Animal Law,” J. Pippin, 54 S. Tex. L. Rev. 469 (2012-2013).

14 The author of this present article generally opposes animal testing, because even if it saves human lives, human beings do not adequately compensate the animals, individually or as a species, who are sacrificed.  

15 See, for example, “Research into a functional cure for HIV in neonates: the need for ethical foresight,” S. Shah, et al, Lancet Infect Dis. (2014 September).

16 FDA Amendments Act of 2007,  section 801. According to FDA, this regulation takes effect in January 2017. “The final rule considers all interventional clinical trials with one or more arms and with one or more pre-specified outcome measures to be controlled clinical trials.” Final Rule, Federal Register p. 64982 (Sept. 21, 2016).

17 Note 3, supra.

Note: The review of Prof. Greenberg's book was actually the second of my book reviews published by the ISBA recently. I thought readers might enjoy my review of Prof. Bob McWhirter's illustrated history of the Bill of Rights, which I wrote last year.

The citation is to the ILLINOIS STATE BAR ASSOCIATION’S HUMAN RIGHTS NEWSLETTER, VOL. 42 #1, SEPTEMBER 2015.

Bills, Quills and Stills offers something for everyone, but most of all the serious scholar

BY JOHN OTROMPKE

ABA Releases a New and Heavily- Illustrated Popular History of the Bill of Rights

Late in the first chapter of Bob McWhirter’s colossal and profuse new book, Bills, Quills, and Stills: An Illustrated, Annotated and Illuminated History of the Bill of Rights, the author makes a fascinating point about the interplay of the two main clauses of the First Amendment.

Pointing to the emergence of the internet, he says, “By any measure, we have more freedom of speech and religion today.” Continuing, he adds, ‘“The media’ seeks
to manipulate us every day, to influence who we vote for to the toothpaste we buy...We need something to help see the lines between the messages we get. That something can be traditional religion, a code of ethics, a philosophy, or principles by which to live. In this sense, even an atheist can have ‘religion.’”

After having read to the conclusion of McWhirter’s opus, a skeptic might propose an addition to that list: what about history?

In fact, McWhirter’s tome manages to combine a thorough and detailed history
of the origins of most of the Bill of Rights with enough scintillating images that almost anyone would want to pick it up, at least for a few minutes- a client in the waiting room of a law office, a junior high school student, teacher or judge- and it also contains such a thorough wealth of scholarly references that it will be of use to the scholar and the practicing lawyer as well.

McWhirter, a supervising attorney at a teaching law firm operated by Arizona State University, as well as an author and experienced litigator, got the idea for the book years ago, when he was assigned to give a presentation to the Arizona State Police and stumbled upon a 1937 reference by Nelson B. Lasson called ‘The History and Development of the Fourth Amendment to the United States Constitution.’

“I was going to write about the history of the criminal law amendments, such as the Fourth, Fifth, Sixth, and Eighth, which I actually use every day, and it became natural to write a book on the history of the Bill of Rights,” said McWhirter, a criminal lawyer who has also authored two books on immigration law.

One of the most interesting insights of the book is that Alexander Hamilton and other federalists believed the Bill of Rights was unnecessary and redundant: why would a federal government of limited powers (such interstate commerce, the suppression of piracy, etc.) ever try to restrict speech or the right to bear arms?

But those who drafted the Constitution knew that Anglo-Americans had taken
great pains over several centuries of English history to acquire a detailed legal history
in which certain rights were preserved, and Madison and others were intent on including them explicitly in the document.

While the first chapter of the book drags a little (sometimes it seems McWhirter is giving us a history of western civilization rather than the First Amendment), by the time he gets to the Second Amendment, the author more than makes up for it with a compelling recapitulation of English history, a wealth of scholarly footnotes, and an inexhaustible fount of imagery.


One is left with amazement at the reflection that some of these concepts (due process, for example) have survived the American Revolution and Civil War, and innumerable civil wars in England, and yet some laws remain unchanged and intact.

Sometimes McWhirter’s footnotes even touch on a topic that seems to compel literary research of its own, such as his argument, all too brief, that a proper understanding of the Fifth Amendment’s takings clause compels reparations for slavery, or that the concept of fundamental law is more rooted in natural law than English history, for example. (“Fundamental law is not just contractual; natural law is that which creates the greatest good,” he tells us, parsing the language of the Declaration of Independence as drafted by Jefferson and then edited by Franklin). While this volume may be too general to focus on a thorough development of such controversies, the serious scholar will find more than enough here to spark the idea for many a thesis.

That’s not to say that the book is flawless. The images can sometimes be distracting, and combined with the footnotes; they usually take up more than half the page. One may question some of the author’s well-established truisms; for example, the author quotes Pericles in the First Amendment chapter to tell us that “[H]appiness...[is] the fruit of freedom and freedom of valor,” but the history so expertly recounted in the rest of the book leads one to wonder if it is not wealth that leads to happiness, while bravery, at least for many of the English personages described by McWhirter, will only get you sent to jail.

Also curiously omitted was a history of the due process clause, at least 800 years old this summer with the recent anniversary of Magna Carta. The book concludes with a brief discussion of the Civil War Amendments (13th, 14th and 15th), which may have been a perfect place to discuss this seemingly all-encompassing concept of due process. But maybe McWhirter is saving such a discussion for a forthcoming volume (his next book, he tells us, will deal exclusively with the Civil War Amendments).

“I consider myself an originalist, but the intent of the framers of the13th, 14th
and 15th Amendments was very broad,” he says. “A lot of people say the framers never intended the constitution to do this, that, or the other. For example, maybe James Madison didn’t intend for you to pay federal income tax, but the framers of the 16th Amendment certainly did.”

All of that said, Bills, Quills and Stills remains one of the most physically gorgeous books ever published by the ABA. For schoolteachers, it is a natural go-to text; for the casual browser, its images and wit will be irresistible; and for serious readers, it is so well researched and annotated that it may find an eternal and irreplaceable slot on the shelves of your libraries or law office. 􏰁

I wrote the following review of Karen Greenberg's book, 'Rogue Justice,' this past spring. It was published in The Illinois State Bar Association’s Human Rights Newsletter, Vol. 43 #2, October 2016.

Book Review

‘Rogue Justice: The Making of the Security State’
Karen J. Greenberg
Crown Publishing, New York, 2016
$28 Hardcover

A Compelling Legal History of a Contemporary Civil Rights Catastrophe

Karen Greenberg’s ‘Rogue Justice’ is a Brief, but Encyclopedic Account of Modern Times 

by John Otrompke

It is a rude awakening to realize that, in the past 16 years, an entire generation in the U.S. has reached young adulthood, without ever knowing life before 9/11. They have lived only during the longest ‘war’ in American history, perhaps inured to a never-ending stream of public massacres. They have been told that Americans have lost our civil rights, but perhaps they can’t really know what that means.

Prof. Karen Greenberg, PhD, does an excellent job of providing a concise, compelling history of the legal aspects of this brutal, dystopian modern era. In ‘Rogue Justice: The Making of The Security State’ (Crown Publishing, New York, 2016), Greenberg, director of the Center on National Security at Fordham University School of Law, unwinds much of the entire narrative in 266 pages.

Every landmark event of this era finds its locus in the text: the 1998 African embassy bombings, the World Trade Center attacks, the passage of the PATRIOT Act, the invasion of Afghanistan, and the second invasion of Iraq . More recent phenomenon are also chronicled: Bin Laden’s killing, the Tsarnaev atrocities in April 2013, the release of the government’s report on torture, and the disclosures of Edward Snowden and Chelsea Manning.

To be sure, Greenberg is a historian, not a lawyer, although she teaches a course on national security issues and the law at Fordham Law School. She touches on almost each facet of the retrenchments in American civil liberties made in the past 15 years, with particular emphasis on the apparently universal secret surveillance, the torture policy, and, ultimately, the extra-judicial killing of American citizens by drones commanded by the president.

The work is unbiased, for the author is very unstinting in her criticism not only of the Bush, but of the Obama administration, too. This slim, well-researched volume also goes into the nitty-gritty of recent legal phenomenon such as indefinite detention without trial, growingly harsh punishments for whistle blowers, undisclosed use of surveillance evidence in criminal prosecutions, and even a body of secret law.

   An International Law Perspective Essential to Evaluating American Foreign Policy

In documenting these developments, Greenberg has given us an inside look at the official policy-shaping acts of influential lawyers inside the executive’s Office of Legal Counsel, and other branches of the federal government, new and old, through successive presidential administrations.  The author has developed this exhaustively-researched history through numerous interviews, personal observation of dozens of trials of jihadists, and even a personal visit to Guantanamo Bay.

Greenberg’s conclusion could be pithily summed up in her statement on p. 40 that the past era has constituted “an undeclared war being waged not on a particular enemy but on an idea, terrorism, which, like most ideas, is probably impossible to eradicate.”

While I admire Greenberg’s work, and respect her methodology, there are some changes I would like to see, should the book go to a second edition. First, while ‘Rogue Justice’ is a popular history rather than a legal text, she touches on enough matters of scholarly and practical interest that the book could use numbered footnotes and better citation to legal authority complying with Blue Book style. 

Additionally, there are several issues under international law, the inclusion of which could supplement Greenberg’s perspective. Shortly after 9/11, for example, some experts said that because Bin Laden was not alleged to be acting on behalf of a nation-state, but instead was international criminals, the U.S. was required to demand the trial or extradition of the perpetrators prior to invading Afghanistan (see, for example, “Legal Control of International Terrorism: A Policy-Oriented Assessment,” C. Bassiouni, 43 Harv. Int'l L.J. 83, (Winter 2002)).

Then, in 2003, there was the Bush administration’s violation of the U.N. Charter when France and other Security Council members disclosed their intent to veto the second Iraq war (“We don’t need a permission slip to defend our country.”) It seems that many of the world’s continuing problems stem from that oft-criticized invasion: ISIS, the deadly refugee catastrophe in Syria, perhaps even a fracture in the European Union.

     Foreigners May Prefer POW Status to Criminal Trial in Federal Court

Additionally, I disagree with one of Greenberg’s primary themes: that the federal courts are preferable as a locus for the trial of enemy combatants or jihadis, compared to courts martial. As Greenberg has written elsewhere:

            “These vexing issues could be far more readily resolved in U.S. federal courts, where  

           handling classified material under the Classified Information Procedures Act is a time-honored 

           and effective mechanism — and where judges have addressed the difficult issues involved in

           terrorism cases for three decades now. In fact, over 400 cases have been prosecuted in federal   

           courts since 9/11.”

“Those 28 pages on the Saudis, and these 5 trials of 9/11 plotters: Are we looking for closure in the wrong place?” K. Greenberg, New York Daily News, May 23, 2016 (editorial).

I doubt if a federal court would be more fair to certain jihadis than the military commissions she describes. As she describes it, the case of Ahmed Ghailani (p. 189) is a powerful illustration of this argument. 

Ghailani, indicted for a role in the pre-9/11 bombings of African embassies in 1998 in which 224 were killed, was tried not by a military commission, but before a federal court in the Southern District of New York. Although indicted on 285 charges, the jury convicted Ghailani of only one: conspiring to destroy property and buildings. He was not of any charges involving the deaths of human beings. Nonetheless, Ghailani was sentenced to life. But from a defense perspective, an act of war by a combatant arguably should not be prosecuted as a crime, unless it’s a war crime. Had Ghailani been treated as a prisoner-of-war, instead of a federal criminal defendant, arguably he could expect to go home some day.

Greenberg also describes another decision favoring a foreign combatant as retrogressive. The conviction of Salim Hamdan by a military commission for material support was  reversed by the D.C. district court after he had served his sentence and been released (p. 248). The federal court found that Hamdan could not be convicted of material support, because that was not a crime when the acts in question took place, long before 2006.  

Greenberg says that the 2012 decision “threatened to bring [progress] entirely to a standstill...The military commissions were not only failing to make forward progress; they appeared to be on the verge of moving backward.” 

The author tells us that today, these cases (when tried) are almost always brought in federal court. But I have grave misgivings about the expanding assertion of universal criminal jurisdiction by U.S. federal courts, especially when the U.S. has repeatedly refused to recognize the universal jurisdiction of other international bodies.  

       Americans Can Be POWs, but POWs Have Habeus Corpus Rights

Perhaps what Prof. Greenberg is concerned about is the prospect of American dissidents being tried by military commissions. After all, Greenberg describes several other recent manifestations of executive totalitarianism, such as surveillance, torture, and extrajudicial disappearances, as well as international aggression.

As a bit of backstory, perhaps one reason that fear has not come to pass (at least not yet) has to do with a series of decisions by the Supreme Court, which, when it has acted at all in recent years, has generally issued opinions supporting principles of humanism and fairness in this context.

As Prof. Greenberg notes, the Supreme Court first held that an American cannot be tried by a military court in the civil war-era case Ex parte Milligan (p. 89). But the High Court reached a different decision during World War II in Ex parte Quirin (p. 65), which was distinguished from Milligan because the Americans being tried by military commission in Quirin had actually been a formal part of the German army.

But a different issue is presented, as Greenberg says, by the important question of whether federal courts have any habeus corpus jurisdiction over POWs at all. Many years ago, the Supreme Court told us no, in the World War II-era case of Johnson v Eisentrager. The individuals in Eisentrager (who were not Americans) could not avail themselves of federal habeus corpus review, because jurisdiction only lay in courts in the jurisdiction in the which prisoners are located. 

So why do federal courts have jurisdiction over POWs today? The principle of Eisentrager was overruled, the Supreme Court told us in Rasul v Bush, by a rather esoteric Supreme Court case from 1973, called Braden v 30th Judicial Circuit Court of Kentucky, which did not involve prisoners-of-war. In Braden, the Supreme Court ruled that a habeus petition can be brought in any district court in which  the custodian can be served, regardless of the location of the prisoner.

That is how foreign combatants came to have access to the great writ: in an act of legal jiu-jitsu, the Supreme Court relied on an obscure 1973 opinion, authored by Justice Brennan, to protect human rights in the midst of the civil liberties catastrophe that followed in the wake of 9/11.

        An Unprecedented Expansion of Freedom in the 21st Century

So for young adults, how has life changed in the U.S. since the PATRIOT Act? Surprisingly, in many ways, Americans are far freer today than we were in 2001. 

In the past era, there were no LGBTQ rights under the U.S. Constitution. Cannabis was universally criminalized here, and the Second Amendment was not thought to protect an individual right to own a firearm. While massacres in the U.S. have become a phenomenon of appalling recurrence and regularity, they have been most often committed by Americans. 

In short, as a matter of visible law, many Americans have been seeing an unprecedented expansion, not a contraction, of our civil rights. This contrasts with the experience of many generations in the Middle East, going back to the period after World War I, for whom American foreign policy was often anything but a boon.

Developments since 2001 make it clear that radical change can be effectuated in the federal courts. When it has acted at all, the Roberts Court has often acted to promote human freedom, sometimes in surprising ways. But a foreign combatant might prefer prisoner-of-war status to a trial in a federal court.

‘Rogue Justice’ is a gripping account of a true history which moves through the history of the past 15 years with the energy of a whirlwind. While I may disagree with one of her themes, Greenberg’s diligent research has made a significant contribution to the legal history of current events.

(c) 2016 John J. Otrompke, JD

One Method of Researching Child Suicides, the Psychological Autopsy, May be Hindered by the Common Rule and IRB Requirements

Child suicides in the U.S. are increasing, yet research is hampered by low incidence and high fluctuation. One method of research, the psychological autopsy (involving interviews of the deceased child's family members) may not be available for universal application due to IRB requirements. This could make it more difficult to understand what is causing an increase in suicides among very young children.

This article, based on a poster at a recent meeting of the American Academy of Child and Adolescent Psychiatry, first appeared on my journalism blog.

I am very interested to explore whether the proposed changes in the notice of proposed rulemaking to the federal Common Rule would effect this regulatory hurdle.