The Fight Against Antimicrobial Resistance: Important recent publications

By Timo Minssen

One of my previous blogs discussed the growing threat of antimicrobial resistance (AMR). I concluded that antimicrobial resistance is a growing and complex threat involving multifaceted legal, socio-economic and scientific aspects. This requires sustained and coordinated action on both global and local levels.

A recent medical review on drug resistant tuberculosis supports these findings and provides further fodder to the debate. In their study, which was published in April 2014 in The Lancet – Respiratory Medicine, the authors analyzed the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medico-legal aspects of extensively drug-resistant tuberculosis and other resistant strains. In particular, the authors discussed the increasing threat of functionally untreatable tuberculosis, and the problems that it creates for public health and clinical practice. The paper concludes that the growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis—and increased funding to strengthen global control efforts, research, and advocacy—even more pressing.

This was also recognized in the recent WHO’s Global Surveillance Report on AMR, which was published this April. It is the first WHO report that studied the problem of AMR on a global level. Noting that resistance is occurring across many different infectious agents, the report concentrates on antibiotic resistance in seven different bacteria responsible for common, serious diseases such as bloodstream infections (sepsis), diarrhoea, pneumonia, urinary tract infections and gonorrhoea. The results demonstrate a wide-spread growth of resistance to antibiotics, especially “last resort” antibiotics. In particular the report reveals that this serious threat is no longer a mere forecast for the future. AMR is a contemporary problem in every region of the world and has the potential to affect anyone, of any age, in any country. Consequently the WHO report concludes that antibiotic resistance is now a major threat to public health that needs to be tackled on a global level.

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Good news for many South African HIV patients—with a big glitch

On Wednesday, South African Health Minister Aaron Motsoaledi announced that, as of January 2015, HIV-positive patients in the country would start receiving free antiretroviral treatment once their CD4 count fell below 500, instead of current threshold of less than 350. Some patient groups would start receiving antiretrovirals immediately upon being diagnosed with HIV infection, regardless of their clinical stage.

Last month, Till Bärnighausen, Dan Wikler and I predicted in PLoS Medicine that sub-Saharan nations would move in the direction that South Africa is now moving, and pointed out a big complication. This policy change might make several gigantic trials of so-called treatment-as-prevention in sub-Saharan Africa impossible to complete successfully. As we explained, these trials remain important for assessing the potential of treatment-as-prevention to curb the spread of HIV in general populations (with many different relationship types and different levels of care delivery and support).

In treatment-as-prevention, antiretrovirals are offered to patients immediately upon their diagnosis with HIV. The hope is that very early treatment would be better for these patients and prevent them from infecting others. We also offered some ways out of this mess, but they involve untraditional approaches to research conduct and to policy. Our piece was featured in the June issue of UNAIDS’ HIV This Month.

When Should you Be Able to Subpoena Clinical Trial Data? “Clinical Trials and the Right to Remain Silent” in JAMA Internal Medicine

Should litigants in products liability or other litigation be able to subpoena data from clinical trials to help prove their case? Does it matter whether the clinical trial is ongoing, finished recruiting but still analyzing data, or published? Michelle Mello and I have an invited commentary on this issue in JAMA Internal Medicine “Clinical Trials and the Right to Remain Silent” with our analysis and recommendations. We are discussing a real case from Yale where a subpoena was sought for data from a placebo-controlled trial of pioglitazone conducted there, where the person seeking the data had sued the manufacturer and believed she had been injured by pioglitazone but was not a clinical trial participant. In the same issue of JAMA IM, Yale gives its own account about how it handled the case here.  Dr. Kernan (the investigator) and I also have a nice interview podcast on the issue

Translating “ELSI” into Policy

by Guest Blogger Wylie Burke MD, PhD.

When the Human Genome Project began in 1990, the National Center for Human Genome Research – now the National Human Genome Research Institute (NHGRI) – created a research funding program for evaluation of the ethical, legal, and social implications (ELSI) of genomics. ELSI scholars study a wide range of issues, from the responsible conduct of genomic research, to implementation and outcomes of genetic testing programs, to intellectual property challenges.  But how should this research be evaluated? In particular, what impact should we expect for this kind of research? These questions are particularly challenging for those of us who work in the multidisciplinary Centers of Excellence in ELSI Research (CEERs) funded by the NHGRI, because these centers have been given a programmatic charge to consider policy-relevant questions and help to inform the policy-making process. A group of ELSI researchers, representing seven CEERs, have been deliberating these questions and recently published a paper with recommendations.

We noted, first of all, that policy-making occurs in many venues. Although discussions often focus on governmental policies, policy-making in other venues often influences genomic translation, including actions as diverse as Institutional Review Board (IRB) decisions about consent and return of results; guidelines promulgated by professional organizations; funding decisions of health insurers; and investment decisions of venture capital.   In addition, policy-making in one arena may influence the need for policies in another. For example, practice guidelines influence the use of genetic testing and may in turn influence how clinical data are accessed to evaluate test outcomes, or how IRBs decide what genetic results should be returned to research participants. Read More

Bumps on the Road Towards Clinical Trials Data Transparency- A recent U-Turn by the EMA?

By Timo Minssen

In a recent blog I discussed the benefits and potential draw-backs of a new “EU Regulation on clinical trials on medicinal products for human use,” which had been adopted by the European Parliament and Council in April 2014. Parallel to these legislative developments, the drug industry has responded with its own initiatives providing for varying degrees of transparency. But also medical authorities have been very active in developing their transparency policies.

In the US, the FDA proposed new rules which would require disclosure of masked and de-identified patient-level data. In the EU, the EMA organized during 2013 a series of meetings with its five advisory committees to devise a draft policy for proactive publication of and access to clinical-trial data. In June 2013 this process resulted in the publication, of a draft policy document titled “Publication and access to clinical-trial data” (EMA/240810/2013).

Following an invitation for public comments on this document, the EMA received more than 1,000 submissions from stakeholders. Based on these comments the EMA recently proposed “Terms of Use” (TOU) and “Redaction Principles” for clinical trial data disclosure.

In a letter to the EMA’s executive director Dr. Guido Rasi, dated 13 May 2014, the European Ombudsman, Emily O’Reilly, has now expressed concern about what seems to be a substantial shift of policy regarding clinical trial data transparency. Read More

“That’s a Lot of Marijuana”

By Nadia N. Sawicki

Earlier this month, the Drug Enforcement Administration issued notice that it would be increasing the 2014 production quota for marijuana from 21 kilograms to 650 kilograms – an almost 3000% increase. In the words of DEA spokeswoman Barbara Carreno, “That’s a lot of marijuana.” This step, according to the National Institute on Drug Abuse (NIDA), was a necessary response to a dramatic increase in current and proposed marijuana research. Read More

SAVE THE DATE: 9/18/14, Post-Trial Access to Medicines: Responsibilities and Implementation

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Please join us for a day-long conference at Harvard Law School on September 18, 2014, which will include presentations by leading experts and varied stakeholders as well as small group discussion and break out sessions that will work toward developing consensus in this difficult area.

Key questions include:

  • How should post-trial access be defined?
  • What type of interventions should be included in post-trial access obligations?
  • What are the responsibilities of various stakeholders?

More information, including the developing agenda, will be posted on the Petrie-Flom Center’s website as it becomes available.

Cosponsored by the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School and the Multi-Regional Clinical Trials Center at Harvard University.

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