Meetings & Minutes

European Science Foundation/University of Barcelona Conference--Pharmacogenetics and Pharmacogenomics: Adverse Drug Reactions

Recent advances in genetic screening will lead to safer pharmaceutical drugs, with reduced adverse side effects, if the methods are incorporated in clinical development. A rallying call to bring key scientists into this growing field of pharmacogenetics, the application of genetics to drug development and safety, was made in July 2008 at a conference organized by the European Science Foundation (ESF) in collaboration with the University of Barcelona and held in the Costa Brava, Spain.

Growing use of pharamacogenetics will not just reduce side effects, but also speed up the process of drug development by helping eliminate unsuitable candidates at an earlier stage and enable researchers to concentrate on the most promising compounds. The potential benefits are therefore enormous, with pharmacogenetics playing a major role in the emerging era of personalized medicine where drugs and treatments are increasingly tailored to the circumstances and genetic makeup of individuals and subgroups within populations. It will complement existing methods, in particular animal testing, which although valuable sometimes fails to identify critical side effects that may be caused by individual genetic traits, or combinations of genes specific to the human species as a whole.

"It was confirmed by the conference that we need to ensure we have the appropriate study designs, including randomized controlled trials, to unravel the complexity of variable drug responses, and we need to embrace the new technologies, such as whole genome scans, to identify novel and known genetic predisposing factors," said the conference chair, Munir Pirmohamed from the University of Liverpool in the U.K.

Side effects can be caused by many factors relating to drug transport, immune response, and sometimes unexpected metabolic pathways, but as Pirmohamed noted, they fall into two main categories, type A and type B.

"The majority (80 to 90 percent) of adverse drug reactions are type A--they are predictable from the known pharmacology of the drug, are dose-dependent, and can be alleviated by reducing or identifying the correct dose for the patient," said Pirmohamed, who gave the example of the anticoagulant warfarin, widely used to prevent thrombosis in susceptible patients by inhibiting blood clotting. But without any blood clotting, patients would sooner or later bleed to death, so clearly warfarin must be given in the correct dose, finding the tight window between dangerous clotting and unstoppable bleeding. The point is that the correct dose varies between individuals, and this is where pharamacogenetics comes in. "Genetic factors can be important here," said Pirmohamed. While type A reactions can often be picked up in animal testing or from general clinical analysis before human trials begin, pharmacogenetics has an important future role to play in establishing the correct dose for individuals.

Type B accounts for most the remaining 10 to 20 percent of adverse drug reactions, including a variety of bizarre or unexpected responses that may be genetically dependent or alternatively shared by all people who take the drug. However, animal testing and other existing methods are much less successful at identifying type B reactions, which are more likely to go undetected until human trials begin. Indeed pharmacogenetics will also play an important role in uncovering these potentially lethal type B reactions, including those involving the immune system's memory cells.

"The immune system is important in adverse reactions, and this conference did focus on certain aspects of predisposition to immune mediated reactions," said Pirmohamed. There was particular interest in the role of the HLA (Human Leukocyte Antigen) system, which directs the production and operation of immunity proteins, and is the source of the individual variation in immune response that leads both to population-wide protection against disease, and rejection of incompatible blood, tissue, or donated organs. This variation in HLA genes can also cause adverse reactions to certain drugs in some individuals but not others, leading in some cases to liver damage, for example.

"It is clear from the conference, and from the findings over the last few years, that the HLA system plays a major role in predisposing to certain immune-mediated adverse reactions," said Pirmohamed. Some drugs cause adverse reactions much more commonly among particular ethnic groups, resulting from particular alleles of HLA genes whose selection has been favored by conditions in a given part of the world. One example is the anticonvulsant drug carbamazepine, used to treat epilepsy, which can cause Stevens-Johnson syndrome. This is a severe allergic reaction causing skin rashes and lesions.

The ESF conference set the stage for developing methods of identifying such adverse reactions in advance by seeking associations between genes that may indicate where unexpected problems or severe reactions may occur. In particular, it helped identify future targets and research objectives, said Pirmohamed, who added, "As with any other conference, the aim is for world class scientists to present their latest work, and for the audience to then consider whether it would be appropriate to incorporate particular techniques or methodologies into their work, and to individually decide how to do it. I know for many attendees, this did happen. It certainly did for me!"

Source: EurekAlert! 9/16/08

CRX08--The 2008 Clinical Research Excellence Conference

The 2008 Clinical Research Excellence Conference (CRX08), focusing on the strengths of the clinical research industry across Australia and New Zealand at conducting early phase clinical trials, was held at the Brisbane Convention & Exhibition Centre in Queensland, Australia in August. The conference was hosted by Nucleus Network, the Queensland Clinical Trials Network Inc., and The University of Melbourne’s Faculty of Medicine, Dentistry, and Health Sciences in cooperation with the Association of Clinical Research Professionals (ACRP), the National Health and Medical Research Council, and the British Association of Research Quality Assurance.

More than 300 attendees and nearly 50 speakers from a wide range of clinical research organizations, universities, trial centers, and industry organizations participated in the three-day program, including globally recognized researchers such as Professors Michael Good, Ian Frazer, Warwick Anderson, and Peter Morley. More than 50 abstracts were submitted for considerations at the conference; from these, 12 authors were invited to deliver special 15-minute oral presentations and 20 were invited to display posters. Four international speakers also provided a global perspective on clinical research, including Deborah Lasher, RN, MPH, CCRC, chair of the Association Board of Trustees for ACRP, who presented on "The International Perspective in Research Certification," "Use of Medical Devices in Research," and "Emerging Markets."

The program highlighted five distinct streams: research, investigators, regulation and policy, indigenous health, and centers for clinical research excellence. A clinical partnerships forum and a series of social functions were integrated into CRX08 to ensure delegates had an opportunity to catch up socially and professionally. An Education Forum provided an opportunity for clinical researchers to share their thoughts on skills, education, and professional development that would provide the best foundations for improving clinical research in Australia and the Pacific Rim region.

The guest of honor at the official opening ceremony was the new Governor of Queensland, Ms. Penelope Wensley, AO. Guests also enjoyed Professor Richard Murray's address at the conference dinner highlighting the need for understanding the additional challenges confronting clinical activities and health researchers in the northern parts of Australia, while at the same time showing how simple some of the solutions can be if time is taken to think laterally and work thoughtfully with local communities.

Nucleus Network represents the Australia Chapter of ACRP and provides internationally respected good clinical practice (GCP) clinical research education and training platforms to the Australian and New Zealand clinical research industry. Nucleus Network is also Australia’s leading clinical research organization for the conduct of early phase clinical trials. The organization has two state-of-the-art, purpose-built early phase clinical trial units (30 and 16 beds) within specialist teaching hospital and research excellence precincts, and provides clinical research consulting services to local Australian biotech start-ups.

ACRP has been represented in the Australia/New Zealand region for approximately four years, during which time, nearly 950 research professionals have been trained in GCP and more than 100 have been involved in ACRP certification programs.

The next Clinical Research Excellence Conference will next be held in Melbourne, Australia in August 2009. All ACRP members are welcome to attend. Please send inquiries to Robyn Lichter, director of education and training for Nucleus Network at r.lichter@nucleusnetwork.com.au.

For more information about CRX08, click here.

U.S. Pharmacopeia's 2008 Annual Scientific Meeting

The U.S. Pharmacopeia (USP) Convention's 2008 Annual Scientific Meeting will be held in Kansas City, Mo., September 24 to 26. The meeting is an opportunity to interact with the USP experts responsible for establishing internationally recognized standards for prescription and over-the-counter medicines, food ingredients, and dietary supplements.

The keynote speaker will be Kenneth D. Mandl, MPH, associate professor at Harvard Medical School and director of the Intelligent Health Laboratory at the Children's Hospital Informatics Program in Boston, Mass.

Experts from USP, the Food and Drug Administration, National Institutes of Health, academic institutions, leading manufacturers, the United Nations, and the World Bank will present information aimed at improving drug, supplement, and food ingredient quality. More than 450 attendees are expected to make the trip to Kansas City this year to attend the cutting-edge sessions, provide feedback, and network with colleagues.

In the wake of recent drug and food safety crises like adulterated heparin and pet food, this year's event will focus on topics such as detecting impurities and heavy metals to work towards preventing these tragedies in the future. General tracks and special topics include Quality of Manufactured Medicines: Impurities, Quality of Manufactured Medicines: General Notices and Process Topics, Quality of Manufactured Medicines: General Chapters & Performance Testing (Microbiology Topics and Packaging Safety Topics), Quality of Manufactured Medicines: Drug Products, Quality of Food Ingredients and Dietary Supplements, Quality of Veterinary Drugs, Drug Safety and Efficacy in Global Markets, and Heavy Metals.

"USP relies on the feedback it receives from scientific experts as we develop standards for the quality, purity, and strength of medicines and food ingredients. [This meeting] is a wonderful opportunity for those who are affected by our standards to participate in the process, which is why the meeting is so important. I look forward to robust discussions with regulators and industry representatives at the meeting as we work together to help ensure the quality and safety of medicines and food ingredients," said Darrell Abernethy, MD, PhD, chief science officer for USP.

Registration is currently open and can be completed online by clicking here. The registration rate is $1,350 per person through September 12. For members of associations, academia, and government, the rate is $650. The registration fee covers the program, meeting materials, breakfast and lunch daily, and all meeting social activities.

The USP is a private, nonprofit, standards-setting organization that advances public health by ensuring the quality and consistency of medicines, promoting the safe and proper use of medications, and verifying ingredients in dietary supplements. These standards, which are recognized worldwide, are developed by a unique process of public involvement through the contributions of volunteers representing pharmacy, medicine, and other healthcare professions, as well as science, academia, government, the pharmaceutical industry, and consumer organizations.

For more information about USP and its four public health programs, click here.

Source: EurekAlert! 9/3/08

Michael J. Fox Foundation PD Therapeutics Conference

The Michael J. Fox Foundation for Parkinson's Research (MJFF) will host its second annual PD Therapeutics Conference on Monday, Sept. 15, in Chicago. Chaired by Jeffrey Kordower, PhD, director of the Research Center for Brain Repair and Jean-Schweppe Armour Professor of Neurological Sciences at Rush University Medical Center, the conference will bring together academic and industry scientists to focus on novel research advances impacting development of improved disease-modifying and symptomatic interventions for the diagnosis and treatment of Parkinson's Disease (PD). Select MJFF-funded investigators will present research on topics including novel neuroprotective agents, innovative mechanisms to address disease symptoms and improvements in relevant animal models, and biomarker discovery/development. In addition to scientific talks, a small poster session will highlight novel targets and animal models relevant to PD research. Confirmed speakers include D. James Surmeier, PhD (Northwestern University), on the FDA-approved diabetes drug that may protect dopamine neurons in the Parkinson's brain; Anders Björkund, MD, PhD (Lund University, Sweden), on the role of serotonin (better known for the part it plays in depression) in dyskinesias, the disruptive movements brought on by long-term dopamine replacement therapy; Erwan Bezard, PhD (Universite Victor Segalen, Bordeaux, France), and Piu Chan, MD, PhD (Beijing Institute of Geriatrics, China), on conducting preclinical and clinical research in China; and Patrik Brundin, MD, PhD (Lund University, Sweden), on the state of cell replacement approaches for Parkinson's disease. Last year's inaugural conference in New York City drew a multidisciplinary audience of nearly 200 academic, pharmaceutical, and biotechnology industry researchers. Funding for the PD Therapeutics Conference has been provided by Elan Corp., plc, Novartis Pharmaceuticals Corp., and the Licensing Executive Society. Source: EurekAlert! 8/7/08

Medical Device Innovators Discuss Next Generation of Implants

“Opportunities for Next-Generation Implants,” the 2008 Materials and Processes for Medical Devices Conference, brought together the diverse innovators who envision, create, and apply devices for cardiovascular, orthopaedic, neurological, and pulmonary applications.

Hosted by Cleveland Clinic and ASM International, and held with the support of BioEnterprise, the forum was attended by surgeons, clinicians, biomedical engineers, device designers, and materials scientists and engineers. The event was held August 5 through 7 at the InterContinental Hotel in Cleveland and was cochaired by Shuvo Roy, PhD, of Cleveland Clinic’s Lerner Research Institute, and Dana Medlin, PhD, of South Dakota School of Mines and Technology.

Surgeons and clinicians provided their perspectives and specific clinical examples; and engineers described the design and manufacturing challenges involved in the selection and applications of materials and coatings, including issues like manufacturability, reliability, and affordability.

The last day of the conference featured presentations by leading experts in failure analysis, who described case studies based on actual device successes and failures. Source: Newswise 8/5/08

2008 Alzheimer's Association International Conference on Alzheimer's Disease

Results from four studies of potential new treatments for Alzheimer's--even an unsuccessful late stage clinical trial--increase the field's knowledge and point scientists toward advances in therapies for the disease, according to research reported July 29 at the 2008 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD 2008), in Chicago.

The reports included data from:

-- A Phase III trial of tarenflurbil (Flurizan, Myriad), an antiamyloid therapy, that failed to achieve its primary endpoints.

-- A 12-week, Phase IIa trial of PBT2 (Prana Biotechnology), which reduces the toxic form of amyloid by preventing the interaction of amyloid with copper and zinc in the brain.

-- A 84-week, Phase II trial of methylthioninium chloride (Rember™, TauRx Therapeutics), a tau aggregation inhibitor that targets toxic tau aggregates, or "tangles." Tangles of tau in the brain are another characteristic hallmark of Alzheimer's.

-- A proof of concept clinical trial in mild Alzheimer's of Souvenaid (Danone Research-Centre for Specialised Nutrition), a "medical food" product that encourages the formation of brain synapses and may reduce beta amyloid.

"While researchers continue to investigate amyloid as a target for Alzheimer's therapies--it is the most mature theory being pursued--we must also examine other potential avenues given the urgency of conquering this disease," said Samuel Gandy, MD, PhD, chair of the Alzheimer's Association's Medical and Scientific Advisory Council. "We can't leave any stone unturned if we hope to aid the 5 million people currently living with Alzheimer's and the millions more that will be devastated by this epidemic."

ICAD 2008 was the largest gathering of international leaders in Alzheimer's research and care ever convened. More than 5,000 researchers from 60 countries shared groundbreaking information and resources on the cause, diagnosis, treatment, and prevention of Alzheimer's and related disorders. As a part of the Alzheimer's Association's research program, ICAD serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community. ICAD 2008 was held in Chicago at McCormick Place, Lake Side Center, from July 26 to 31.

For more information about ICAD 2008, click here.

2008 BIO International Convention

The 2008 BIO International Convention, held recently in San Diego, Calif., drew 20,108 industry leaders from 70 different countries and 48 states to discuss and share the latest developments and most pressing issues facing the biotech industry. The convention featured the largest gathering of biotech exhibitors in history, with more than 2,100 companies and 80 pavilions within the BIO Exhibition. For a first-hand account of the biotech industry's visit to San Diego, check out the convention website here.

Europe's Leading Pharmacologists Meet in Manchester

Hundreds of leading pharmacologists and bioscientists from across Europe met in Manchester, U.K. in July for the 5th Congress of the Federation of European Pharmacological Societies. Hosted by the British Pharmacological Society, EPHAR 2008 had a packed programme of plenary lectures, cutting-edge symposia with subject-leading speakers, and satellite meetings and trade exhibitions. The four-day meeting showcased the research of leading scientists from EPHAR's 24 affiliated pharmacological societies and promised to be the most important international pharmacological event of the year. Key themes included reducing risk in drug discovery and development, respiratory pharmacology, pain and inflammation, and pulmonary and cardiovascular pharmacology. The gathering closed with a lecture on drug provision for the developing world by world-renowned political philosopher, Professor Thomas Pogge. For more information about EPHAR 2008, click here.

SLEEP 2008 Overview

More than 5,500 sleep medicine physicians, sleep researchers, sleep technologists, and others involved in the sleep field gathered in Baltimore in June for the 22nd annual meeting of APSS, the Associated Professional Sleep Societies (SLEEP 2008).

SLEEP 2008 commenced with a plenary session that included an awards ceremony, a presentation on the National Heart, Lung, and Blood Institute's 2008 strategic plan, and a keynote address on “Sleep, Dreaming and Consciousness – A New Paradigm.”

At the annual membership meeting, Dr. Mary Susan Esther was installed as the 23rd president of the American Academy of Sleep Medicine (AASM). In her address, Dr. Esther outlined her goal for her tenure: ensuring balance. Embracing the diversity of the membership and their professional interests, Dr. Esther reaffirmed the AASM’s commitment to academic sleep medicine, clinical practice, and research, and stressed her goals of working closely with the Centers for Medicare & Medicaid Services and independent carriers on policies as well as promoting the sleep medicine physician. The Board of Directors for 2008 to 2009 was also installed at the meeting.

At SLEEP 2008, the AASM launched an initiative to help members and accredited centers across the country establish and incorporate state sleep societies. A session provided attendees with information they need to organize at a local level and to run an effective state society. A separate session was a forum for members to discuss local regulatory policies and legislation as well as ongoing initiatives in state government.

Two days of postgraduate courses marked the beginning of the scientific program. This year’s program included 17 symposia, four discussion groups, seven clinical workshops, 18 meet-the-professor lunch sessions, eight invited lecturers, 36 brief oral presentation sessions, and more than 900 poster presentations.

The invited lecturers at SLEEP 2008 were among the most notable names in the field. Dr. Ronald Grunstein presented “Managing Sleep Apnea – Are We There Yet?” and Dr. Ronald Szymusiak lectured on “Hypothalamic Regulation of Sleep Onset and Sleep Maintenance.” Dr. Charles Czeisler talked about “Sleep and Circadian Rhythms in Humans: Tales of Translation from the Lab to Practice” and Dr. Colin Espie addressed “Treating Insomnia with CBT: Should We Step Up to Stepped Care?” Dr. Christopher Early discussed “Restless Legs Syndrome: From the Bed to Bench and Back Again” and Dr. Terri Weaver explained “Not Tonight Honey! The Effect of Sleepiness on Daily (or Nightly!) Functioning.”

This year, 159 companies displayed the latest products, goods, and services available for the sleep field. The exhibit hall, which was the largest to date, enabled attendees to learn more about the latest therapies available for sleep disorders, get first-hand demonstrations of products, and interact with sales staff. The exhibitors also introduced new trends and offered a glimpse of future trends for the field.

Next year, SLEEP 2009 will be held June 6 to 11 in Seattle, Wash., with AASM Past President Dr. Michael Sateia serving as Chair of the APSS Program Committee.

Source: American Academy of Sleep Medicine 6/19/08

In Rare Move, FDA Reclassifies Device Type

According to information found in the May 30 issue of the Federal Register, the Food and Drug Administration (FDA) is reclassifying the device type known as "tissue adhesive for the topical approximation of skin" from Class III (Premarket Approval) into Class II (Special Controls). Tissue adhesives for nontopical uses remain in Class III and continue to require premarket approval applications (PMAs). FDA is proposing this reclassification in accordance with the Federal Food, Drug, and Cosmetic Act. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled ``Class II Special Controls Guidance Document: Tissue Adhesive for the Topical Approximation of Skin,'' which will serve as the special control for the reclassified device type. This final rule is effective June 30, 2008.
The Minneapolis-based organization Regulatory and Clinical Research Institute, Inc. (RCRI) had petitioned the FDA to down-classify tissue adhesives for topical approximation to the skin from Class III to Class II. According to RCRI, out of 17 petitions of its kind in the last six years, this petition represents one of only two reclassifications petitions that the FDA has approved.
Representing a leading manufacturer in the medical industry, RCRI developed the petition and presented the case to FDA’s General and Plastic Surgery Devices Advisory Panel. RCRI and leading experts offered significant evidence supporting the safety and effectiveness of this device type, as well as evidence that the design and manufacturing of such tissue adhesives was controllable and well understood. As a result, RCRI proposed that general and special regulatory controls will be adequate to provide reasonable assurance of the safety and effectiveness of future tissue adhesives, and therefore the regulatory oversight requirements of Class III devices, including the PMA submission, are no longer necessary.
The panel unanimously agreed and recommended the reclassification of tissue adhesives for the topical approximation skin from Class III into Class II, and that a guidance document that includes several voluntary consensus standards serve as the Special Control for the reclassified device type. The FDA agreed with the panel’s recommendation, and after periods of review and public comment, this Reclassification Order has been granted concluding that these devices will now be cleared for commercial distribution via a Premarket Notification 510(k) submission rather than a PMA. As suggested by the Special Controls guidance document, this will mean that clinical trials will likely only be required for external tissue adhesives utilizing new materials, new technology, or new indications.

Impressions of a First-Time Attendee at the ACRP Global Conference

I attended my first Global Conference in Boston this year. Prior to arriving, I was somewhat bewildered by the complexity of the agenda. After arriving, I was impressed by how elegantly this vast and diverse scope of presentations unfolded.

For a number of reasons, I found this experience to be engaging. There is one reason in particular that I would like to mention: I was struck by the juxtaposition of lectures on scientific topics and lectures on humanistic topics. There were scientific presentations on erudite subjects such as genomics, proteomics, and microarrays. On the humanistic side, there were ethical discussions regarding such topics as informed consent and conflict of interest. There was even a presentation on humour in the research industry (sadly, one that I missed).

Medicine, even today, can still be defined as the art and science of the advancement of human health. By extension, medical research also contains both elements. The APPI seal reflects this duality. On it, science and humanity are both addressed. There is the staff of Aescelapius along with a Latin inscription, "melior valetudo per scientia." This translates to "better health through science."

Conference discussions reflected these two elements in varying proportions. In certain areas of medical research, these two elements of science and art can even have polarizing effects. This tension was well demonstrated in a lively debate regarding conflict of interest. When promoting this debate in the April issue of The Monitor, Dr. Jonathan Seltzer predicted: "Expect fireworks." I was not disappointed. Both sides were brilliantly argued, one from primarily an ethical standpoint and the other from primarily a scientific standpoint. For medical research to advance safely, we should continue to foster both.

With my past classical education failing me, I returned to my hotel room after the last presentation and used my computer to get the Latin translation of the APPI inscription on the seal. I "googled" valetudo and found that, if written as two words, vale tudo, it means in Portugese "anything goes"—something that I will point out at next year's presentation on humour.

Submitted by Robert Jeanfreau, MD
Metairie, La.

The European Forum for Good Clinical Practice Annual Conference 2008 on Safety in Clinical Trials—Are We in Jeopardy?

For a report on this conference, which was held 29–30 January 2008, Résidence Palace, Brussels, Belgium, click here.

The development of new medicines depends on a host of different factors, but chief of these is exposure of human subjects to new compounds the effects of which, at first, are largely unknown. It is only by conducting clinical trials that these effects are revealed, some of which will be unwanted. The discipline of clinical research, however, is governed by one of the most stringent legislative frameworks within our society, designed to protect human subjects taking part in such research. Even so, risks abound and the history of unexpected crises is a vivid memory within the clinical research community. How can all those taking part in the clinical research process best meet these challenges? How is the safety of research subjects to be safeguarded?

AFROGUIDE: A Pan-African and International Project on Guidelines for Health Research in Africa

The AFROGUIDE Project on Guidelines for Health Research in Africa was launched by experts and policymakers from Africa and the international community during a roundtable on health research facilitated by the Good Clinical Practice Alliance – Europe and the Cameroon Bioethics Society at the "Science with Africa" conference organized by the United Nations Economic Commission for Africa and the African Union in Addis Ababa, Ethiopia, on March 4–7, 2008.

African countries suffer from a disproportionately high percentage of the global disease burden while possessing remarkably low investment in health research. Clinical trials and other directed research engagements are particularly important for finding new prophylactic, diagnostic, and therapeutic interventions that will address prominent diseases on the continent, such as HIV/AIDS, tuberculosis, malaria, sleeping sickness, and cancer. This health research needs to be supported by clear guidelines in Good Clinical Practice, informed consent, ethical review, genetics, pediatrics, and other areas, taking into account the specific needs of African communities and the continent as a whole.

The project partners represent high level expertise in health research and health policy. They include the Good Clinical Practice Alliance – Europe, a Brussels-based not-for-profit organization with leading expertise in the creation of guidelines in ethics and clinical research as well as model law development and adaptation; the Cameroon Bioethics Society, based in Yaoundé, which has played a parenting role since the late 1980s in the development of ethics and research on the African continent; and Science for Development, a not-for-profit organization with expertise in the application of science to needed areas of development in policy and in society.

The primary objective of the AFROGUIDE Project is the development and implementation of model laws and guidelines for health research in African countries with the aim of strengthening African legal and regulatory systems for health research while advancing the development of health policy on the continent.

This overall objective is achieved through the following specific objectives:

• developing a comprehensive database on existing guidelines and legal frameworks in the context of health research in all African countries, including frameworks on ethics, biomedical research, clinical trials, and gene research;

• achieving stakeholder support, in particular from African countries, through the organization of meetings in Africa, Europe, the U.S., Asia, and Latin America;

• drafting guidelines with experts from African countries, international institutions, and industry in the fields of clinical trials, ethics, pediatrics and special populations, biomedical research, and genetic research;

• supporting the development of a model law to be adopted at the African level and implemented into national legislation and practices; and

• supporting the development of political will to realize the adaptation and implementation of the guidelines into the policies and practices of African countries.

The project objectives will be achieved through the following work packages:

WP1 (Survey) This work package gathers comprehensive information about the existing guidelines and legal frameworks on health research in all African countries. The information is collected and organized on a publicly accessible Internet database.

WP2 (Fundraising) This work package focuses on raising the necessary financial resources for the project. The resources are used to finance the secretariat and to organize the meetings, including flight and accommodation costs for the African and international participants. The project follows stringent rules on transparency and conflict of interest.

WP3 (Networking) This work package brings together leading stakeholders by developing communication, education, and interaction structures. Networking structures provide for an essential capacity-building structure to ensure cross-fertilization and impact across all regions and sectors of the Africa communities.

WP4 (Guidelines Development) This work package concerns the development of model laws and guidelines from the inception of ideas, through drafting in working parties and across consultations, to their editing and cross-referencing and publication and translation.

WP5 (Guidelines Implementation) This work package implements the model laws and guidelines into law, policy, and practice at the continental, regional, national, and local levels. It also provides for adaptation, feedback, and eventual revision of the original model laws and guidelines.

The AFROGUIDE Project advances and facilitates health research across Africa, contributing to the development of health across African communities.

Submitted by Francis P. Crawley
Executive Director, Good Clinical Practice Alliance – Europe

An Overview of Recent SACHRP Actions

The Department of Health and Human Services (HHS) Secretary's Advisory Committee on Human Research Protections (SACHRP) met on March 27 and 28, 2008. Agenda items over the two-day period were essentially 1) discuss issues surrounding research and quality assurance activities; 2) evaluate the recommendations of the Subcommittee on the Inclusion of Individuals with Impaired Decision-Making Capacity in Research (SIIIDR); 3) review recommendations on research in disaster areas; and 4) review recommendations from the Subpart A Subcommittee.

For the first agenda item, the advisory committee heard testimony from a panel consisting of Donald Berwick, MD, MPP (president and CEO of the Institute for Health Improvement), Brent James, MD, MStat (executive officer for the Institute for Health Care Delivery Research and chief quality officer for Intermountain Health Care), Carolyn Clancy, MD (director of the Agency for Health Research and Quality), Christine Grady, MSN, PhD (head of the Section on Human Subjects Research Department of Bioethics at the National Institutes of Health Clinical Center), and Nancy Neveloff Dubler, LLB (director of the Division of Bioethics at Montefiore Medical Center and professor of bioethics at Albert Einstein College of Medicine's Department of Family and Social Medicine).

After presentations, the advisory committee members and the public were allowed to question the panelists and offer further comment. Although much of the discussion pulled from the "Keystone study" between Johns Hopkins and the Michigan Hospital Association and the HHS Office for Human Research Protections' (OHRP) actions there and their impact, the committee remained focused on not trying to figure out who was right or wrong in that case, but focused on what the committee can do to assure that healthcare providers can provide the necessary ethical quality improvement while also protecting the rights of patients and research subjects. There was a general consensus that there were "quality improvement operations" and "quality improvement research" and that, instead of regulations, HHS could provide guidance on the differentiation as to when a quality assurance/improvement activity is research or not.

The SIIIDR then presented its summary of activity and recommendations. It reviewed a summarized version of the comments received from the RFI posted by OHRP, the comment period for which ended in July. The chair of the subcommittee (David Strauss, MD) presented its recommendations, which consisted of no additional regulations, but requested guidance be issued by OHRP that addresses several key issues. The first was that a concept of "consent capacity" be defined; the second was that detailed recommendations should be drafted related to identification of individuals who may lack consent capacity, understanding that this was not directed to specific clinical diagnoses, but to a current state of capacity independent of diagnosis. Additional items included a request for further clarification of what a "Legally Authorized Representative" is, and the role of surrogate decision makers. The subcommittee also recognized many local levels have a void in this area, and discussed the need for the development of a "model state legislation" or other appropriate approach. The committee also recommended that the drafters be cautious that such guidance not be an inhibitor of enrollment.

For research in disaster areas, the advisory committee recommended that HHS create policy in this area. It was generally recognized that research involving humans in the aftermath of disasters was critically important for individual and societal benefit, and that HHS should be proactive to promote its planning. The committee members were (and requested such regulations be) cognizant of the concerns that research not distract from the provision of aid in disaster areas. Additionally, they asked that regulation provide the mechanism to protect subjects while still allowing research to be executed in a time-sensitive manner. They also recommended that the process involve relevant input from potentially affected governmental agencies and other stakeholders, as well as the public.

Daniel Nelson, MS, CIP, and Elizabeth Bankert (of Dartmouth College, filling the expiring term of Felix Gyi, PharmD, CIP, of Chesapeake Research Review), cochairs of the Subpart A Subcommittee, re-presented the assumptions of the committee about inappropriate interpretation/application of the Subpart A regulations imposing administrative burden without meaningful human subject protections, also noting that associated practices do not enhance the safe and ethical conduct of research due to diversion of resources. The subcommittee had previously worked on a list of 29 recommendations to Subpart A and furthered its review of a few of these items to the full advisory committee. Specifically, additional clarifications on each of the criteria for exemption were determined to be needed and discussed, and changes were requested to the requirements for institutional review board roster change reporting to OHRP. Additional recommendations will be presented at a later date on waiver of documentation of consent.

It is always important to note that the discussions and decisions made at SACHRP are neither law nor guidance. They are facilitated to produce recommendations in an advisory capacity to the Secretary of HHS, who will act accordingly.

Submitted by David Vulcano, MSW, LCSW, MBA, CIP
Vice Chair, ACRP Association Board of Trustees