Saturday, November 29, 2014

Health Canada Badly Fails Canadians at Risk for HIV Infection

A surprising tweet landed in my inbox some time late yesterday afternoon. Health Canada issued a 'warning' about OraQuick in Home HIV Test. It's currently available for sale on the Canadian site of Amazon. Now, you might think, what qualms could one possibly have about Health Canada issuing a warning about this HIV self-test kit? It might be untested, not doing what it promises to do, etc etc. Makes sense then that the agency 'has initiated compliance and enforcement actions', as it notes darkly on its website, showing its regulatory teeth where it purportedly matters. In any case, you might think, why don't people use a self-test kit that has actually been approved by the agency?

Here the plot thickens. Turns out, 'there are currently no HIV test kits authorized by Health Canada for home use.' In other words, our regulator has chosen not to authorize any HIV self-test kits for use by us. Your guess is as good as mine as to why this hasn't happened. Perhaps our draconian and control obsessed public health agencies want to prevent individual access to self-tests. Perhaps there is an assumption by the medical establishment that we're just too daft to administer the self-test. Perhaps there are mistaken assumptions about our ability to cope should the test results give us reasons to be concerned. Countries such as the United States, and the UK as well as quite a few others have given regulatory approval for these test kits. Apparently competent adults are not treated like children in other parts of the world.

So, what about OraQuick's home HIV test? Let's see, here are customer reviews at US pharmacy chain CVS's website. Yep, it's a 5***** product. People who have used it love it. Well, as we all know, people also love homeopathy, so this tells us little about whether a product is good or works. Let's go then to a regulatory agency that, unlike Health Canada, actually does its job. The United States Food and Drug Administration has approved this home test in 2012.

As I said earlier, I don't know why Health Canada is doing such a lousy job on this front and doesn't evaluate and approve HIV home test kits. They work, they are known to be used widely and they serve to make people more knowledgeable about their HIV status who might - for reasons best known to them - do not wish to inform our Public Health Agency of their HIV status. These people are put off testing by the need to see a doctor and get a script to get tested for HIV. This obviously undermines important public health objectives. Fewer people at risk for HIV infection will get tested. Some HIV positive people will remain ignorant of their status and likely pass on the virus to sex partners. It is public health foolishness not to make access to HIV testing as easy as possible. This, of course, conflicts with the never-ending control freakery public health professionals are notorious for.

I understand why Health Canada needs to act on unregistered products being sold in the country. However, there are products and products. This particular product has been approved for use by a serious, better resourced and arguably better functioning regulatory agency than Health Canada, the FDA. Health Canada has failed for years to test (and approve) this particular product. To now go on a twitter campaign and on an enforcement campaign to prevent the sale of this product in the country suggests seriously wrong priorities at the agency. Meanwhile Canadians tired of this nonsense are at least able to hop across the border, go into any pharmacy they fancy and be treated like actual adults. The product triggering Health Canada's 'compliance and enforcement' activities is on the shelves there. Apparently Health Canada has the resources to engage in compliance and enforcement this-n-that, testing and approving sensible products? Not so much.

How about focusing on actual bogus products or products known to be harmful?

Tuesday, November 25, 2014

On peer review

The debates among journal editors and other academics about the merits or otherwise of particular forms of peer review continue. A growing number of academics in the STEM subjects seem to think that post-publication peer review provides for higher quality control than the traditional post-submission pre-publication review. Their logic is that mistakes in manuscripts are less likely to be found during a process involving only a handful of reviewers. They furthermore argue that post-publication peer review will submit journal articles to scrutiny by a much larger number of readers. Methodological, statistical and other mistakes would almost certainly be found out in post-publication scrutiny with a higher likelihood simply due to the much larger number of expert reviewing (ie reading, analysing and commenting on) manuscripts post publication. It is difficult to argue with this contention, except to note that post publication peer review sites today suggest that only some of the manuscripts there receive such desirable academic community review. What does this proposal mean then for papers that are ignored altogether by peers. Will they still count as some kind of peer reviewed publications or are they just blog-equivalents? Who counts as a reviewer? Would the authors’ best friends be viable options? University administrators and appointments committees will want to know.

Of course, traditional peer review doesn’t preclude post-publication review. It happens that manuscripts that passed pre-publication review are eventually found to be seriously methodologically flawed. Many of those are withdrawn, but reluctant publishers and editors have also gained notoriety by leaving flawed manuscripts in the public domain without errata. Post-publication review depends to some extent on easy access to the manuscripts in question (Open Access being a bonus here), as well as the existence of sophisticated web-based moderated platforms permitting reader-peers to leave comments. It goes without saying that relentlessly profit-driven publishers of academic journals will be reluctant to invest in the staff necessary to manage this process.

I think, for humanities manuscripts, for the time being, pre-publication anonymous peer review remains the way to go. Anonymous peer review guarantees honest reviews from reviewers. Open review, whereby the reviewers and authors are disclosed to each other, will often prevent honest reviews, simply because reviewers inclined to be critical of a particular submission will be reluctant to burn their bridges by speaking frankly to the quality of a particular submission submitted by a close colleague or friend. Anonymous reviews are not in their own right a guarantee of quality. That’s where journal editors step in. They need to evaluate reviewers’ comments and decide what to do if reviewers’ verdicts vary significantly. You might be surprised to learn that this does not happen all that frequently. Reviewers almost always reach similar verdicts.

The challenge today is, of course, to find knowledgeable reviewers. I have lamented this problem here before. Senior colleagues are often reluctant to undertake this vital work. In fact, a few of them refuse to undertake reviews outright. That does not stop them from complaining bitterly if their manuscripts are, in their view, in the review process for an extraordinary amount of time. Perhaps we ought to institute a policy whereby as editors we would be well within our right to refuse to evaluate submissions from colleagues routinely unwilling to accept review requests.

Another issue arises when it comes to sourcing true peers to review particular content. Having now been an Editor of this journal and its companion journal for the last 15 years, I still struggle on occasion to find a suitable competent reviewer for a particular manuscript. It takes time, especially if the subject matter of a particular manuscript is highly specialised, to find the right peer reviewer. At this journal as well as its companion journal our standard operating procedure is that we as Editors have to find appropriate reviewers. We ask authors only in the rarest of exceptions to suggest possible reviewers to us. It turns out that choosing our own reviewers is a good idea, more so than we thought it is. Journals who ask authors for reviewer suggestions have been hit in fairly significant numbers by fake reviews, written under pseudonym by submitting authors, or by commercial outfits in the business of drafting fake reviews.[i] Post publication peer review publications should take note. You never stop learning when it comes to these matters, and sadly, nothing much surprises me any longer. The public or perish culture in today’s universities has clearly led to unreasonably pressures on academics, leading quite a few of us to stray from the right path.

Courtesy of the rise of open access on-line ‘journals’ we have reason to be weary of claims that the papers published in many such venues have been peer reviewed. As I write this, several incidents were reported where bogus papers have been accepted for publication by such outlets, for a processing fee, of course, delivered to the ‘editor’ via PayPal. Bound to be a classic is undoubtedly this one: The authors conjured up a fake paper with the title ‘Get me off your fucking mailing list’, directed at a SPAM Open Access outlet inviting contributions. Their paper was accepted, ostensibly after peer review.[ii] As any academic with a university affiliation will be able to testify to these days, the same outfits don’t discriminate as editors of more discerning journals would, in terms of competence to review particular academic outputs. A journalist employed at an Ottawa based newspaper reports that his submission of a fake article to a dodgy Open Access outfit ended up with him being now inundated with requests to review manuscripts he is utterly unqualified to review for said ‘publisher’.[iii] It is fair to say that on the odd occasion every editor will call on the wrong reviewer for a particular submission, but that is usually caught by the second or third reviewer, usually the invited reviewer declines. Apparently many pay-for-play Open Access publishing operations are primarily concerned about extracting author processing fees out of the submitting authors. That they can only achieve after they accept submitted content.

An issue remains apparently the Conflict of Interest declaration. There are all sorts of standards deployed by all sorts of publishing outfits, grant giving bodies and so on. Let me just say that I think reviewers would be well advised to err on the side of caution when they declare conflicts of interest. One good yardstick would be to ask yourself whether, if you were at the receiving end of your review, you would want to be advised (as an editor) of particular information that you are considering disclosing. Conflicts of interest could include knowledge of the authors’ identity, financial conflicts, but also that you might be an author harshly criticised or praised in the manuscript that you are reviewing. None of this would disqualify you per se from reviewing, but knowing about these potential conflicts would help editors to assess your comments more competently.
It is pretty obvious to anyone who has been in the business of publishing as an author or editor – or both – that anonymous peer review is far from perfect, and it is conceivable that new publishing platforms will eventually lead to the rise of better peer review processes. I for one am looking forward to those.

[i] Ferguson, C. 2014. It’s happened again: Journal cannot rule out possibility that author did his own peer review. Retraction Watch November 10. [accessed November 25, 2014]

[ii] Bealls, J. 2014. Bogus Journal Accepts Profanity-Laced Anti-Spam Paper Scholarly Open Access November 20. [accessed November 25, 2014]

[iii] Spears, Tom. 2014. How my fake science paper earned me a shot at an editor's job.  Ottawa Citizen. November 25. [accessed November 25, 2014]

Friday, November 14, 2014

Canadian judge rules that First Nations child's survival interests don't matter more than parental choice

In what has been described as a precedent setting case a Canadian judge has decided today that First Nations parents are well within their right to remove her child from hospital care and place it in an alternative healing outfit (registered in Florida as a massage parlour!). The 'doctor' practicing there has no medical qualifications.

Here's the background of the case: The child suffers from childhood leukemia. Standard chemotherapy has a 95% likelihood of complete remission of the cancer. The family in question has decided instead to transfer the child to an alternative healing facility. The child in question is 11 years old. The local Children's Aid Society decided not to intervene, because the parents were providing 'care' to their child. Apparently to the Children's Aid Society it didn't matter at all what the evidence of success for the parental 'care' was. Turns out that it is non-existent. Another First Nations child also 'treated' in said alternative healing facility has since experienced a serious deterioration in her health because leukemia has returned with a vengeance courtesy of the quack treatment meted out by the Florida based quack healer on behalf of the parents. The family paid close to 20,000 $ for the non-treatment of their child by the Florida based operator of said massage parlour.

Remarkably, the judge in the case seems to be buying into the postmodern relativism that drives the argument of the Children's Aid Society. Here's what the National Post reports from the trial

"But Justice Gethin Edward of the Ontario Court of Justice suggested physicians essentially want to “impose our world view on First Nation culture.” The idea of a cancer treatment being judged on the basis of statistics that quantify patients’ five-year survival rate is “completely foreign” to aboriginal ways, he said.
“Even if we say there is not one child who has been cured of acute lymphoblastic leukemia by traditional methods, is that a reason to invoke child protection?” asked Justice Edward, noting that the girl’s mother believes she is doing what is best for her daughter.
“Are we to second guess her and say ‘You know what, we don’t care?’ … Maybe First Nations culture doesn’t require every child to be treated with chemotherapy and to survive for that culture to have value.”

This sounds almost farcical. The judge apparently doesn't think child survival is what's at stake, but the value of First Nations society. A nice sentiment so long as you aren't a vulnerable child desperately needing proven medical care. He is also essentialising aboriginality in an indefensible way. Here's what the CBC reports about the logic underlying his decision, 'Edward ruled that the young girl needs protection, but that the court had also to consider how aboriginal family rights apply in the case. As part of that consideration Edward described the traditional Haudenosaunee creation story to point out that the practice of traditional medicine existed before contact with Europeans.' The one thing that clearly doesn't feature at all as a relevant criterion is that thing some call 'scientific evidence'. Creation stories apparently trump that at any time.  - Surely, the essential question here is this: Should we, as a society override parental care decisions for their children in cases where there is overwhelming evidence that they're harming their children irreversibly, or, as in our case, where the children would die almost certainly?

The long and short of it is that we have always done this. The children's (objective) best (survival) interests trump parental best intentions, parental ignorance, parental fanaticism, parental scepticism with regard to mainstream medicine etc etc. Hospitals routinely override parental decisions by Jehova's Witnesses that refuse life-preserving blood transfusions for their children. And they are right to do so. There is no parental right to kill their children, not even with the best of intentions. Anyone recall the cases of children who died because their parents thought prayers would do the trick?

What is not known is whether these two cases (same hospital) are a result of a communications break-down between the health care professionals and the parents. But even if this was the case, it remains shocking that the Children's Aid Society could possibly justify its inaction with the view that the parents were just trying something different. Since when has the life of a child become so cheap that we leave it to misguided parents who wish to do as they see fit, evidence be damned?

The apparent 'justification' here is that it is a First Nations child. If this is a case of trying to make-up for past injustice, let me just say that this isn't quite a sensible way to go about this matter.

Seems a classic 'only in Canada' kind of event where society falls over itself trying to accommodate even the greatest nonsense. Child welfare clearly isn't that much of a priority. I'm glad to see that the hospital where both children would have been successfully treated took this case to court. Only once the courts of the land decide that child welfare isn't a relevant consideration and that parental good intentions intentions and the value of 'aboriginal culture' supersede child welfare concerns, can they make future treatment decisions that override patient well-being concerns.  

I do hope that the hospital will appeal this decision.

Tuesday, November 11, 2014

Placebo controlled trials, catastrophically ill patients and access to experimental drugs

Here's the long version of a piece I wrote on this topic for  The Conversation where it was published today (sans a few bits and pieces that I would have liked included). Interestingly enough, the site saw it fit to alert readers of my piece to an article expressing a different point of view. Fair enough, except, when you read said article you'll note that it doesn't link back to my piece.

In the last six months Colorado, Louisiana, Missouri, Michigan and, most recently, Arizona have passed “right to try” laws that allow terminally ill patients to access treatments that have only passed FDA Phase I clinical trials. All patients need is permission from a drug company and a prescription from a doctor.
Right to try laws are designed to ensure that terminally ill patients taking part in clinical trials are true volunteers and have no incentive to cheat the clinical trials system as has happened in the past.
Recently, these laws have been critiqued as misguided, and the ethics of allowing patients to use experimental drugs are still up for debate. These laws do not guarantee access to experimental treatments and patients may have to pay for them out of pocket.
Critics of these laws worry that alternative trial designs, or access to such experimental drugs outside the clinical trials system will significantly delay the development of effective therapies.
Right to try laws are ethically defensible because they give desperately ill patients a choice. They can decide to participate in placebo controlled clinical trials or to access experimental agents as a possible last-chance treatment. The clinical trial system demands that participants are true volunteers. But, without right to try laws, terminally ill patients have no choice but to access these experimental treatments through placebo controlled trials.

AIDS and the origins of ‘right to try’

Throughout the 1980s, AIDS activists and patients fought to change the clinical trials system. Dying from what was then a terminal illness, many people with AIDS insisted on the right to access experimental drugs that had successfully passed Phase I clinical trials.
Phase I trials are designed to establish the toxicity profile of a particular drug. A small group of volunteers (often not more than a handful) test the drug to find out whether it has serious side-effects. They don’t have to be patients, because the objective is to determine what negative effects, if any, the short-term use of the experimental agents could have.
The only option for AIDS patients in the 1980s was to join a post-Phase I placebo controlled trial or go without access to experimental agents that might give them a shot at survival. These drugs trials are typically double-blind. Double-blind means that neither the doctors nor the patients know who receives the experimental agent and who receives the placebo. This aims to eliminate any bias that might arise from patients or doctors knowing who receives what.
Taking part in clinical drug trials meant that AIDS patients faced the chance of being assigned to the placebo control group, and not the group receiving the experimental treatment. These patients understood perfectly well the steep odds against these drugs working. But at least there was a chance. The same cannot be said of placebos.
There is a sound methodological reason to test a new experimental agent against a placebo control when we have no gold standard of care. We need to know whether the new agent does better or worse than the existing standard of care. Even in cases where there is no effective or well-developed standard of care we are usually, but not always, justified in undertaking placebo controlled trials.
But, we expect patients participating in clinical trials to be true volunteers. Patients need to choose to participate and give first person voluntary informed consent.
AIDS patients charged that the clinical trials system was essentially coercive. To access experimental treatments, these patients were more or less forced to take part in these clinical trials. If they did not volunteer to participate in a placebo controlled trial, they couldn’t access experimental treatments.
Many patients grew frustrated with this system and, often in collusion with their doctors and pharmacists, lied and cheated to access particular clinical trials. They analyzed who got placebos and who got the experimental drugs, and shared the drugs. Patients dropped out of clinical trials they believed offered trial designs not conducive to their own survival. Controlled trials become nearly impossible under such circumstances.
Undoubtedly this made it harder to get a sense of what drugs worked and what didn’t and may have delayed the development of life-preserving anti-HIV medication.

Drug companies control access to experimental treatments. Taiyo FUJII/Flickr, CC BY

Right to try, but not right to access

Since the 1980s special access protocols have been implemented in the United States, Canada and other countries. These protocols meant to ensure that catastrophically ill patients can access experimental agents outside the clinical trials’ system.
At least in theory. In practice, things are different. Right to try laws do not guarantee the right to access experimental treatments. Even with laws in place, access is still controlled by drug manufacturers.
In Canada the government permits people with terminal illnesses to access drugs that are in the clinical trials system, and they can do so without having to participate in the trials. In return they promise to have their doctors monitor the impact of the drug carefully and report it back to the manufacturer or whoever runs the clinical trial.
Access to these treatments depends on the goodwill of pharmaceutical companies keen on recruiting patients into their clinical trials. Drug manufacturers effectively coerce terminally ill patients into their trials by refusing access to the experimental agents. Experimental drugs are sometimes released outside of clinical trials on so-called compassionate grounds, but that doesn’t always happen. Here is just one example of a since deceased cancer patient. Adrienne Cotton died earlier this year. She tried to access a particular experimental drug that was already in a phase 3 clinical trial (we had reasonable evidence that it worked against the cancer that was killing her from phase 2 clinical trials). The medication she was successfully denied access to by the drug's manufacturer has since received market approval as a cancer drug in Japan.
And who pays for these experimental treatments? For good reasons insurance plans in the US (or, in Canada, government programs assisting uninsured patients) will not pay for drugs that are untested and are not known to work. As a result of this patients in both Canada and the US must pay out of pocket for these experimental agents.
Pharmaceutical companies are free to charge whatever they wish for these agents, and so, arguably, are in a situation to exploit financially desperate dying patients. This also gives them an opportunity to deny patients access in order to coerce them into trial participation. Regulators need to look at this problem as a matter of urgency.

Ebola patients subjected to placebo controlled trials

FDA officials and influential former NIH staffers are currently falling over one another propagating placebo controlled trials to test experimental agents on Ebola virus infected patients in West Africa. It goes without saying that impoverished catastrophically ill patients there – in the real world – have no alternative other than to accept the deal on the table. There are methodologically sound alternative trial designs available that do not rely on placebos, yet – much like during the 1980s – the FDA remains intransigent to the human suffering caused by its edicts. Remarkably, trial designs that are not acceptable unless alternative access to the experimental agent is offered in a bunch of of US states are foisted so on desperate African trial participants if the FDA has its way.

Monday, November 10, 2014

Another review of 50 Great Myths About Atheism

Courtesy of the author, Diesel Balaam. It was originally published in the pages of the Pink Humanist, on page 15. The magazine is published by that wonderful Pink Triangle Trust, an organization of which I am proudly a Patron.

50 Great Myths About Atheism
Russell Blackford & Udo Schűklenk Wiley Blackwell
ISBN 978-0-470-67405-5
Richard Dawkins was spot-on, when he commented that it was useful to have all 50 myths about atheism listed in one book (having encountered all but 3 of them himself), so Blackford and Schűklenk's book will be invaluable to any atheist who comes up against charges that range from the challenging "Atheists are Certain There is No God" via the insulting "Atheists are Intolerant" to the downright pernicious "Atheists are to Blame for Religious Fundamentalism".
The need for such a book is perhaps a little mystifying to those of us living in the north western corner of Europe, where to declare oneself an atheist generally excites little controversy - at worst, it causes minor irritation to some, akin to declaring oneself a Chelsea supporter. Outside of ethnic minority circles, atheism (or more accurately, secularism) appears to be the modus operandi of the vast majority of citizens, who distance themselves from, and distrust, overt religiosity, certainly of any Abrahamic stripe. Nonetheless, Blackford and Schűklenk quickly broaden out from a slightly US-centric starting point to encompass a wider perspective that includes Muslim countries where the safety of declared atheists really is precarious.
Blackford and Schűklenk provide an informed, reasoned, and calmly dispassionate deconstruction of the many myths used to try and discredit the atheist position, whether those myths are borne of genuine misunderstandings, or desperate cynicism. In particular, the risible - if tenacious - arguments, deployed against atheists by Dinesh D'Souza, a prolific "religious apologist" (as the authors describe him), are systematically unpicked throughout the book and exposed as ill thought-out, flawed and cynical. This is of particular relevance to gay atheists and secular humanists, as D'Souza's starting point is that we became atheists just to swerve the Almighty's opprobrium for our sexual immorality!
The authors' ability to summarise a complex argument is impressive. For example, at the end of their detailed deconstruction of Myth 39 "Atheism Depends on Faith, Just the Same as Religion" they roll their entire argument into just 34 words: "Atheism is not a faith position because atheists do not require something extra that can be called 'faith' to bridge the gap between experience of the world and extraordinary beliefs about a transcendant realm". How cool is that? This book will help many an atheist fortify their position, as well as provide the means to articulate it more effectively.
50 Great Myths About Atheism is thorough, meticulously reasoned, and impeccably well-referenced and researched; its avoidance of jargon and academic grand-standing shows this was intended to be a very accessible book and is all the more welcome for it. The authors are sparing in their use of witty asides and mockery, no doubt anxious to avoid the charge of facetiousness, although the inclusion of some choice Jesus & Mo cartoons for the succinct illumination of various points does add a lighter discursive dimension to the book.
Perhaps some will find the authors' approach slightly too dispassionate and cautious at times. Myth 28 inadequately deals with Hitler's alleged atheism (he was, in fact, professing his ambivalent faith well into the early 1940s - nor is any mention made of those rather more tangible "Gott Mit Uns" Wehrmacht belt-buckles), while in Myth 29 the reader will detect some pussy-footing hesitancy to criticise the followers of Islam. Arguably, rhetorical questions are also over-used (see Myth 31 "Atheists are Intolerant"). Indeed, in his assessment of the book, Richard Dawkins states that "the long final chapter treats theological arguments with more respect than I would have bothered with".
Nonetheless, in spite of its Hush Puppy liberalism, assembling 50 Great Myths About Atheism into one book like this was the authors' master-stroke, a neat and dynamic way of organising and unifying what could otherwise have been a rather disjointed atheist treatise. This is what ultimately gives the book its authority and immediate appeal as a "go-to" source for any atheist who is in a hurry to marshall good contrary arguments, in order to defend their position against any pushy religionist who feels their elaborate nonsense of choice is under threat.

Wednesday, November 05, 2014

Well-intentioned OA journal bites the dust

There seem to be broadly three types of Open Access (OA) journals (and I won't bore you with green, gold and other fancy colours here). In my world, there are journals that are owned by dodgy OA publishers, they likely make the bulk of existing (pardon me, non-existing) OA journals, then there are commercially successful behemoths like PLoS and biomed central, and last but not least there are well-intentioned efforts by academics aiming to break the stranglehold of subscription based journals on their discipline.

There no need to say much about the dodgy publishers, there's a reasonably comprehensible list maintained for that purpose. There is also little to say about PLoS and biomed central. They have managed to get their hands on the pots of cold funders typically empty over STEM subject research grant holders. Typically they charge an article processing fee sometimes approaching thousands of dollars to maintain their infrastructure, and, if they're for-profit, to keep their shareholders happy. There's no equivalent to these sorts of pots of gold in the arts and humanities, yet academic and policy debates about OA are typically driven by STEM folks who are ignorant of the different circumstances faced by academics in the arts and humanities disciplines. Pay-for-play would render many academics unable to publish peer reviewed content in those disciplines.

So, the pay-for-play (aka OA) campaigns quietly forget to tell us who'd give us the money to play under the new OA regimes proposed generously everywhere. Unsurprisingly, research funding councils haven't made up for the in-the-future unnecessary expenditures on journal subscriptions by handing over pots of gold to libraries so that they can fund OA publications. Really what is being shifted here is the responsibility for the financing of research publishing to academic researchers, across disciplines, regardless of the funding situation in those disciplines.

The last group of OA initiatives tries to address this. It relies on academics exploiting themselves in order to maintain the publishing infrastructure that commercial publishers typically maintain (for a steep price). As one would expect of well-intentioned academics they initially offer the having-your-cake-and-eating-it option whereby they maintain the journal infrastructure free of charge, until they eventually fold up or begin charging. The having-your-cake-and-eating-it thingie never tends to work that well in the real world.

A case in point here is the demise of Canada's Open Medicine journal. It was set up as an OA alternative to the Canadian Medical Association Journal after the latter experienced a major scandal involving the publisher interfering with its editor's and editorial board's editorial independence. The journal initially tried to be both OA as well as free of charge, but decided (too late) to begin charging article processing fees. After 8 years and undoubtedly many volunteer hours by its excellent editors, it closed reportedly its door today. The editors note with gratitude the thousands of volunteer hours given to the journals by its supporters. At the risk of coming across as an ungrateful brat gloating over the well-intentioned journal editors' failure, it isn't clear to me at all why academics would want to get into the operational side of the journal publishing enterprise in the first place. As an editor of the equivalent of a monthly journal I can assure you that it takes a lot of time to just deal with the content aspects of journal production.

As far as I can see, this tale is telling. Either you end up with a commercially sustainable business model (PLoS or biomedcentral like), where costs eventually are still incurred at very significant scale, just not by libraries but by authors (in fact, the greater your research output the bigger the financial hit you take!), or you accept that subscription fees will remain a necessity to maintain professional academic journal publishing output.