Debbie Indyk

Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data

UNLABELLED Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%. PERSPECTIVE This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long-term benefits and risks of this treatment.

De Minimis Risk: A Proposal for a New Category of Research Risk

De Minimis Risk: A Proposal for a New Category of Research Risk Rosamond Rhodes a , Jody Azzouni b , Stefan Bernard Baumrin c , Keith Benkov a , Martin J. Blaser d , Barbara Brenner a , Joseph W. Dauben c , William J. Earle c , Lily Frank c , Nada Gligorov a , Joseph Goldfarb a , Kurt Hirschhorn a , Rochelle Hirschhorn d , Ian Holzman a , Debbie Indyk a , Ethylin Wang Jabs a , Douglas P. Lackey c , Daniel A. Moros a , Sean Philpott e , Matthew E. Rhodes f , Lynne D. Richardson a , Henry S. Sacks a , Abraham Schwab g , Rhoda Sperling a , Brett Trusko a & Arnulf Zweig h a Mount Sinai School of Medicine b Tufts University c The Graduate Center, CUNY d New York University Medical School, CUNY e Union Graduate College f Pennsylvania State University g Indiana University, Purdue h University of Oregon (Emeritus)

An Ethical Exploration of Barriers to Research on Controlled Drugs

We examine the ethical, social, and regulatory barriers that may hinder research on therapeutic potential of certain controversial controlled substances like marijuana, heroin, or ketamine. Hazards for individuals and society and potential adverse effects on communities may be good reasons for limiting access and justify careful monitoring of these substances. Overly strict regulations, fear of legal consequences, stigma associated with abuse and populations using illicit drugs, and lack of funding may, however, limit research on their considerable therapeutic potential. We review the surprisingly sparse literature and address the particular ethical concerns pertinent to research with illicit and addictive substances, such as undue inducement, informed consent, therapeutic misconception, and risk to participants, researchers, and institutions. We consider the perspectives of key research stakeholders and explore whether they may be infected with bias. We conclude by proposing an empirical research agenda to provide an evidentiary basis for ethical reasoning.

The Rationale of Interorganizational Linkages to Connect Multiple Sites of Expertise, Knowledge Production, and Knowledge Transfer: An Example from HIV/AID S Services for the Inner City

Summary This paper presents the rationale for a long-running project in which various community-based and tertiary-based providers are being linked to each other in order to understand, reach, and engage high-risk, hard-to-reach inner-city residents for prevention, treatment, and management of HIV/AIDS. Not simply a program to link disparate actors, the work has developed into a more fundamental approach through which to build and maintain the infrastructure required to generate and sustain knowledge development and integration within and between systems. This work is grounded in the recognition that each type of provider, as well as patients and clients themselves, has a particular type of expertise. All forms of expertise are necessary to fight HIV/ AIDS. Different forms of expertise are necessary to diagnose, treat, prevent, and cure HIV/AIDS and its sequelae. This work suggests revisions in traditional approaches to expertise and to the content and geometry of dissemination networks, and ultimately challenges the very concepts of dissemination and the lay/scientific boundary.

The STARK study: a cross-sectional study of adherence to short-term drug regiments in urban Kenya.

Summary The purpose of the STARK study (Short-Term Adherence Research in Kenya) was to identify factors that predict adherence to short-term drug regimens in Nairobi, Kenya. The participants (N = 357) in the study were recruited from the RAFIKI Foundation Clinic, a free primary healthcare clinic in Kibera, Nairobis largest slum. Quantitative surveys were administered to all the participants regarding their adherence patterns and to a subgroup of mothers (N = 233) regarding their adherence in giving medicine to their children. Forty participated in four focus groups. Fifty-two percent of participants reported taking all of their prescribed medication and 47% took it until they felt better. Over 65% of mothers reported giving all prescribed medication to their children. The most frequently cited barriers to adherence included lack of food and clean water, stress, and financial problems. By identifying obstacles to adherence and strategies to overcome them, this study showed that a community-based clinic with committed healthcare workers in Kenya can empower an economically disadvantaged population to be adherent.

Micronutrients in HIV: A Bayesian Meta-Analysis

Background Approximately 28.5 million people living with HIV are eligible for treatment (CD4<500), but currently have no access to antiretroviral therapy. Reduced serum level of micronutrients is common in HIV disease. Micronutrient supplementation (MNS) may mitigate disease progression and mortality. Objectives We synthesized evidence on the effect of micronutrient supplementation on mortality and rate of disease progression in HIV disease. Methods We searched MEDLINE, EMBASE, the Cochrane Central, AMED and CINAHL databases through December 2014, without language restriction, for studies of greater than 3 micronutrients versus any or no comparator. We built a hierarchical Bayesian random effects model to synthesize results. Inferences are based on the posterior distribution of the population effects; posterior distributions were approximated by Markov chain Monte Carlo in OpenBugs. Principal Findings From 2166 initial references, we selected 49 studies for full review and identified eight reporting on disease progression and/or mortality. Bayesian synthesis of data from 2,249 adults in three studies estimated the relative risk of disease progression in subjects on MNS vs. control as 0.62 (95% credible interval, 0.37, 0.96). Median number needed to treat is 8.4 (4.8, 29.9) and the Bayes Factor 53.4. Based on data reporting on 4,095 adults reporting mortality in 7 randomized controlled studies, the RR was 0.84 (0.38, 1.85), NNT is 25 (4.3, ∞). Conclusions MNS significantly and substantially slows disease progression in HIV+ adults not on ARV, and possibly reduces mortality. Micronutrient supplements are effective in reducing progression with a posterior probability of 97.9%. Considering MNS low cost and lack of adverse effects, MNS should be standard of care for HIV+ adults not yet on ARV.

The shifting locus of risk-reduction: the critical role of HIV infected individuals.

Summary This article discusses the shifting locus of control over risk-reduction and examines its implications for the care and support of HIV-positive individuals. We begin by presenting a brief history of the continuum of HIV related risk, illustrating the ways in which advances in risk-assessment and intervention have led to this important shift. Second, we discuss the current state of risk assessment and intervention as it relates to three factors: (a) the point along the continuum of risk at which risk assessment and intervention occurs; (b) the locus of control over risk reduction; and (c) the distinction between primary and secondary risk reduction efforts. Finally, we discuss the meaning of HIV risk and the role of HIV-positive individuals in the new geometry of care that integrates treatment and prevention. How is HIV-risk defined and understood? Who is of risk to whom? Who is responsible for reducing risk?

Wiring the HIV/AIDS system: building interorganizational infrastructure to link people, sites, and networks.

Summary This paper presents a case example of the new “geometry of care” (Rier and Indyk, this volume), by examining selected examples from five facets of a program developed by the lead author and in operation since 1989. This program is designed to understand, build, revise, and maintain the organizational infrastructure with which to link diverse players and sites, and combine these into a web for producing, assessing, and exchanging the information needed to combat HIV/AIDS. Each example demonstrates how opportunities were exploited for developing and linking resources within and between systems of care and prevention. The program began as an iterative and systems approach to improve access of high-risk, hard-to-reach inner city New York populations to HIV/AIDS services, treatment, and research. The approach is also currently being further elaborated and applied in Argentina and India (see Boylan et al., this volume), and is adaptable to other local and global public health challenges (see Indyk & Rier, this volume).

Requisites, benefits, and challenges of sustainable HIV/AIDS system-building: where theory meets practice.

Summary This paper is the third and final of a series that has previously presented the rationale (Rier and Indyk, this volume) and major program elements (Indyk and Rier, this volume) of an approach to link community and tertiary sociomedical providers, clients/patients, sites, and systems into an integrated response to HIV/AIDS. The primary goal has been to improve sociomedical HIV/AIDS services for a hard-to-reach inner city population. The current paper first summarizes the main advantages (e.g., greater efficiency; more realistic, effective programs with greater credibility among the community; stimulation of knowledge production and dissemination amongst players rarely formally engaged in such activities; creation of a platform useful for other applications) of this work. It then examines some of the main organizational challenges in conducting the work (involving issues such as personnel, coordination, funding, turf conflicts, sustainability). From this discussion emerge organizational requisites to conducting this work (e.g., development of key boundary-spanning figures; attention to the specific interests of potential linkage partners; translation efforts to demonstrate the value of participation; a continuous quality improvement approach featuring wide distribution of feedback in user-friendly form; flexibility, tact and patience), so that others can adapt and apply the linkage approach to manage HIV/ AIDS or other problems. Finally, we explain how theory and practice have driven one another in this work.

HIV-infected individuals as partners in prevention: a redefinition of the partner notification process.

Summary Over the past ten years, the advances that have turned HIV into a chronic illness have also highlighted the importance of integrating prevention and care in the fight against the epidemic. This integration involves not only the creation of new programs, but also a reexamination of the process through which services and supports are provided. In this article, HIV partner notification is used as a case example; the discussion includes: the shifting time frame within which partner notification occurs; the expanding role of HIV-positive individuals in effecting both disease management and prevention goals; the connection between partner-notification and behaviorally-based risk reduction; and the ethical implications of advances on the partner notification process. The authors argue that partner notification services must be located in the context of overall treatment for infected individuals, and demonstrate how a redefinition of the partner notification process can serve as a spring-board for ongoing prevention counseling and support.