Laurence A Goldberg
More than 17,600 delegates, including 822 from 46 overseas countries, attended the 41st Midyear Clinical Meeting of the American Society of Health-System Pharmacists (ASHP) at the Anaheim Convention Centre, California, in December 2006. One hundred and five sessions offered a menu of more than 300 hours of programming, and over 380 companies participated in the exhibition.
Clinical pharmacist recognised
In the opening session, David Angaran (Assistant Director, Experiential Programs, College of Pharmacy, University of Florida, Gainesville) received the ASHP award for distinguished leadership in pharmacy practice for his dedication to quality improvement in hospital pharmacy, managed care, specialty pharmacy and academia. As one of the pioneers of clinical pharmacy in the USA, he played a role in helping to establish clinical pharmacy services in the UK in the late 1970s. He worked at the University of Manchester and Hope Hospital, Salford, as part of an academic exchange programme and assisted in the development of the first clinical pharmacy master’s degree in the UK.
Marvin Shepherd (Director, Center for Pharmaco economic Studies, University of Texas, Austin), who also received an award from the ASHP for his leadership role in protecting the US public from counterfeit, diverted and substandard medicines, described several techniques that are available for validating the authenticity of pharmaceutical products. These include encrypted serial numbers for each package that can be validated by the manufacturer, overt labelling technologies such as holograms, colour-shifting ink or raised print, forensic techniques using minute quantities of inert, easily identifiable additives (taggants) and a variety of covert methods such as invisible inks, micro magnetic wires and computer chips (radiofrequency identification [RFID]). Dr Shepherd said that some of the counterfeit medicines that have been detected have been made in the USA and have entered the legitimate supply chain, but most are made outside the USA and are smuggled into the country and then illegally placed in the distribution network. In addition, counterfeit medicines have been found in US homes, having got there by way of foreign and domestic internet pharmacies. According to the World Health Organization (WHO), counterfeit drugs are estimated to comprise 1-10% of the world market, but this depends on the country and region. In developed countries the figure is claimed to be less than 1%, but the figure rises to 10% in some developing countries and as high as 30% in Africa, parts of Asia and Latin America. The market size is estimated to be $30-40 billion (see Resources).Dr Shepherd went on to say that in spite of enforcement efforts counterfeit medicines continue to plague the drug distribution system. As a worldwide problem it is growing at about 13% annually, and by the year 2010 it is estimated that it will be a $75 billion industry.
The US Food and Drug Administration (FDA) wants to introduce a drug pedigree system for 2007. The overall goal is to develop a system that will protect the public and ensure drug product integrity. It is proposed that each package (bottle, unit dose, patient pack) should have a unique serialised number (licence plate) that can be authenticated throughout the supply chain. Barcodes or RFID tags will be a means of identifying these numbers. Dr Shepherd concluded by saying that RFID is now with us and will become the norm, but although barcodes have serious limitations they are not likely to disappear in the near future. They will continue to be used, and eventually they will serve as a backup to RFID.
A practical five-step evidence-based medicine process for the clinician was described by Patrick Bryant (Director, Drug Information Centre and Clinical Professor, School of Pharmacy, University of Missouri, Kansas City [UMKC]). With practice, it should be possible to complete the process in 10-20 minutes, he told the audience. The advantages of the UMKC process are that it has been modified specifically for pharmacy clinicians making drug therapy decisions, it is rigorous and it categorises evidence logically without being too complex to apply. The five steps are:
- Defining the clinical question.
- Searching for pertinent literature.
- Evaluating the literature critically.
- Determining the quality of evidence.
- Developing recommendations with justifications.
Defining the question is an important step; experience at UKMC has shown that on 85% of occasions the question that is eventually addressed is significantly different from that which was first asked. It takes time to work out the real question, and pharmacists need to understand the context of the question and the scope of the issue or problem, said Dr Bryant.
Most pharmacists are able to carry out the literature search but are less confident about determining the quality of the evidence. A list of 10 major considerations is used to analyse the evidence that has been retrieved (see Box 1). Each can be a strength or limitation depending on the evidence.
The statistical power of a study becomes important when a difference between two groups is not detected. In the absence of a power calculation it is impossible to say whether a real difference could have been detected, and this is a major limitation. If a power calculation was performed but insufficient numbers were recruited then, again, this is a major limitation, explained Dr Bryant.
Five levels of evidence are recognised: level 1 corresponds to interventional trials where the power requirement is met; level 2 is where the power requirement is not met; levels 3 and 4 are observational studies, where level 3 is prospective and level 4 is retrospective; and level 5 refers to case studies, where there are no controls or randomisation. Level 1 evidence forms the basis for the strongest recommendations, and level 5 for the weakest. Evidence should be sorted by level and by the presence of major limitations. When drafting recommendations, Dr Bryant suggested that clear statements should be made concerning efficacy, safety, special considerations or populations, and cost. This approach is useful not only for clinical decision but also for keeping abreast of developments in clinical practice, he concluded. Evidence-based guidelines potentially influence the care of large numbers of people, and so they must be based on solid, reliable evidence, explained Heather Pace (Assistant Director, Drug Information Center and Assistant Clinical Professor, School of Pharmacy, UMKC). Guidelines should always be carefully evaluated to avoid the application of biased guidelines that might not work in practice, she continued. Guidelines may be evidence-based or consensus-based, relying largely on expert opinion. Occasionally, it is possible to find existing guidelines that fit one’s needs perfectly, but it is more usual to find outdated guidelines or guidelines that do not quite fit. Good places to find guidelines include professional organisations, appropriate government bodies and the guideline clearing house (see Resources). Two tools that can be used to ï¿½evaluate guidelines are AGREE (Appraisal of Guidelines Research and Evaluation) and COGS (Conference on Guideline Standardization) (see Resources). The AGREE tool assesses the quality of the evidence but the method of development, whilst the COGS tool is useful for guideline development but does not assess the quality of the guideline, noted Dr Pace. The process for updating a guideline should follow the method described by Dr Bryant. It is essential to conduct a thorough search first and then to evaluate the levels of evidence carefully. At the end of this process the original guideline may or may not be changed, depending on the weight of evidence. Firm recommendations can only be made if there are rigorously controlled trials on which to base them, otherwise recommendations must be cautious, said Dr Pace.
Asked how to tackle the situation in which there are two meta-analyses with conflicting conclusions, Dr Pace recommended that the studies included in the meta-analyses should be retrieved and carefully checked and the process for inclusion should be checked.
Medication safety reports
Two reports concerned with medication safety that had been published at about the same time made far-reaching recommendations for the safe use of medicines, according to Michael Cohen (President, Institute for Safe Medication Practices, Huntingdon Valley, Pennsylvania). “Preventing Medication Errors” and “The Future of Drug Safety” were published by the Institute of Medicine (IOM) and the FDA, respectively. Key recommendations of the FDA report included:
- The introduction of the “black triangle” mark for new products (as is done in the UK).
- A formal review of the risks and benefits of a product five years after launch.
- A moratorium on “direct-to-consumer” advertising during the first two years after the launch of a new product.
- Clear authority and enforcement tools available to the FDA to ensure industry compliance with label changes and conditions.
The IOM report (see Resources) contains a detailed review of the most relevant publications concerning medication errors and concludes that, as yet, not enough is known about the patterns of medication errors. The report also makes numerous recommendations to improve the safe and effective use of medicines.
Handling hazardous drugs
The risks of occupational exposure to hazardous drugs, in particular cytotoxic drugs, could increase as the population ages and cytotoxic drugs are used more widely, for example for non-cancer indications and in veterinary oncology, said Thomas Connor (Research Biologist, National Institute for Occupational Safety and Health [NIOSH], Cincinnati, Ohio). Hazardous drugs have been defined by NIOSH (see Box 2), and at present 140 drugs are included in this category. Two-thirds of these are ï¿½antineoplastic drugs, and the remainder are antivirals, immunosuppressants and monoclonal antibodies. The main concerns when handling hazardous drugs are the risks of acute toxicity, reproductive or developmental effects, cancer and genotoxicity. Currently, 51 cytotoxic drugs are recognised to pose risks during pregnancy, but 46 of these are “category D” (for which the benefits outweigh the risks) and only five are “category X” (for which there is clear evidence of fetal damage). There is some evidence of reproductive and developmental toxicity in healthcare workers; a systematic review had identified two significant studies concerned with spontaneous abortions and two concerned with fetal malformations. No studies concerned with stillbirths had been identified. There was limited evidence for increased cancer rates in healthcare workers exposed to cytotoxic drugs, and no studies of this type had been conducted in the USA. Dr Connor concluded that, because of the ubiquitous nature of contamination with hazardous drugs, proper engineering controls,administrative controls and personal protective equipment should be in place at all times where hazardous drugs are handled.
WHO.IMPACT, November 15 2006, Counterfeit Drug Update Report
National Guideline Clearinghouse
Appraisal of Guidelines Research and Evaluation Collaboration
Shiffman RN, Shekelle P, Overhage JM, Slutsky J, Grimshaw J, Deshpande AM. Standardized ï¿½reporting of clinical practice guidelines: a proposal from the Conference on Guideline Standardization. Ann Intern Med 2003;139:493-8
Institute of Medicine of the National Academies
NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and other Hazardous Drugs in Health Care Settings [DHHS (NIOSH) Publication No. 2004-165]