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About this chapter
The aim is to help pharmacists working in different settings to identify, evaluate and use their own evidence-based sources for improving outcome of patient/client care.
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Evidence-based Pharmacy was first published as a textbook by Phil Wiffen in 2001. The first chapter was published in Eur J Hosp Pharm 2013;20:308–12
We describe strategies for assessing your potential sources for evidence-based medicine information, that is, what resources can you use and trust? Dependent on the type of question (selecting medication, route/dose individualisation or follow-up on effects) we help you to navigate among local, national and international information sources from healthcare providers, authorities and commercial sources; from written publications, internet databases, and smartphone Apps. We base our assessment on patient and client cases.
In previous chapters we have described the fundamentals of evidence-based medicine and pharmacy practice including asking the right questions, tools for searching literature, calculating effect sizes and appraising the evidence. In this chapter, we aim at helping pharmacists to assess and use evidence applicable for their local practice and environment. But can we trust and use local, regional, national and international guidelines, recommendations and information?
We focus on the perspective of selecting, individualising and ensuring follow-up for the best treatment outcomes for a patient (client, customer etc). The aim is to optimise prescribing that is, medication appropriateness. A research tool has been developed for measuring this, the Medication Appropriateness Index (MAI).1 The tool evaluates each drug based on ten items; indication, drug effectiveness, correct dosage, correct directions, practical directions, drug–drug interactions, drug–disease interactions, drug duplication, duration of treatment and expense. Each drug is rated as appropriate (A), marginally appropriate (B) or inappropriate (C) for each of the ten items in the analysis. According to a weighting scheme, a summed MAI score between 0 and 18 can be produced for each medication, and a patient's personal MAI score can be calculated by summing the scores of all medications for each patient.
Different evidence-based sources of information have different aims. Before looking for the evidence you need to think about what kind of support you need. This is the focus for this chapter and is summarised in box 1. For each selected resource you also need to think about whether you can trust and use it. In the previous chapter an appraisal tool with ten questions to make sense of clinical guidelines is presented. There is also a document from the Agree II Consortium (http://www.agreetrust.org) and from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (http://www.gradeworkinggroup.org/) to assist in developing and assess recommendations. GRADE is quite complex, but pharmacists need to know of its existence. box 2 gives a summary of questions to ask about your potential sources.
What is your question, what type of source is needed for optimising patient treatment?
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Selecting medication
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Common disease state or symptom
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Rare disease state or symptom
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Individualise already selected medications
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Route and administration form
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Dose
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Follow-up
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Effects, adverse effects, other problems (ie, identify, solve and prevent drug-related problems)
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Adherence
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Questions to ask for an information source to be evidence based
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Can we trust it?
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Is it up to date?
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Is the content based on best available evidence (eg, a systematic review)?
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Is the process for the preparation fully described and transparent?
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Are important experts, users and customers involved?
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Are conflicts of interest (COI) declared and taken account of?
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Can we use it?
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Is it easy to read, understand and apply?
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Does it give us information to improve patient care?
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In this chapter, we do not discuss in detail the selection of generic compared to innovator products. Of course, there can be problems with information, adherence, double-doses and so on, leading to problems that reduce the cost-effectiveness benefit. All pharmacists also know that there can be differences between individual batches of all medications. As presented in box 3 there can of course also be differences between different products. However, the differences between approved products and batches are normally very small compared to all other interindividual and intraindividual variations when a patient takes a medicine.
Differences between different products
Devit have summarised 2070 bioequivalence studies for generics approved by FDA in a 12-year period.2 The geometric mean ratios and SDs was 1.00+0.06 for Cmax and 1.00+0.04 for AUC. The average difference in Cmax and AUC between generic and innovator products was 4.35% and 3.56%, respectively. Additionally, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%.
Sources for selecting medication
As described in box 1, sources for selecting medication are often different for a common disease state or symptom compared to a rare one. The five cases presented below represent different types of questions where a pharmacist is expected to respond based on evidence-based principles.
But what is the main source for your information? The optimal sources should be easily available, fast and easy to assess, reliable and take account on local effective practice and priorities. General conditions for different sources are summarised in table 1.
Can we use and trust our sources
Practicing EBM is ‘about integrating individual clinical expertise and the best external evidence’.3 It is also ‘the responsible provision of drug therapy for the purpose of achieving definite outcomes that improve a patient's quality of life, that is, according to the initial Hepler and Strand definition of Pharmaceutical care.’4 If you have a patient or client with a common disease state or symptom you can expect to find some local, regional or national recommendation. For a rare disease state or symptom, you are unlikely to find such recommendations, and have to rely on other available resources or to search the literature for individual studies or even case reports, that is, ‘the best available external evidence’.
Finding, assessing and using evidence-based information for improving client health requires professional skills. The rarer the disease the more skills are needed since you normally have to search for and interpret original publications. Therefore, it is important to learn to use and trust reliable EBM resources. Local, regional or national recommendations and guidelines can be very accessible in various forms such as on a computer or as a clinical decision support (CDS) in, for example, computerised order entry (COE) system. This saves time, requires less skills to use, and is often readily available.
Can you trust and use the information?
Based on the information provided in table 1, the best source for information on selecting medication could be recommendations and guidelines produced by your local or regional healthcare provider if based on evidence-based sources and adapted to the local situation. As a pharmacist or any other health professional, you must assess whether the information is trustworthy and useful for your client. For easier and practical appraisal, the questions in box 2 can be used and appraised by you based on some relevant cases from different practices as presented below.
Case 1
You are working as a clinical pharmacist in a nursing home and are performing a medication review for Christina, 75 years old. Christina is slightly demented, but independent and spirited. She can walk with the help of a walker and is doing great, has partially dysphagia, and gets jelly diet.
Three years ago, she had a stroke, and last year a hip fracture. She is getting Aspirin 75 mg once a day, paracetamol (acetaminophen) 500 mg three times a day and calcium-vitamin D (600 mg/400IE) once a day. You found a bone density measurement with a value of minus 2.5 measured 2 years ago.
Is the treatment for preventing further fractures optimal for Christina?
Case 2
You are working as a clinical pharmacist in an internal medicine department at a University Hospital. The patient, Gregory, 90 years old, has been admitted due to haematuria, tachycardia and tiredness. He has several medications and you are performing a medication review. You can initially not find an indication for Allopurinol 100 mg. On Gregory's’ medication container it is stated ‘prophylactic against gout’. You can find that the patient previously had slightly elevated urate plasma levels but no gout attacks. Is Allopurinol 100 mg an optimal treatment for Gregory?
Case 3
You are working in a pharmacy close to a healthcare centre, and Steve, 65 years old, is collecting his prescription drugs for Parkinson disease. The medications are levodopa/carbidopa 100/25 mg four times a day, and ropinerol 1 mg three times a day. Steve tells you about his major problems with shaking and asks you whether propranolol can help him. His neighbour uses it for shaking problems but does not have Parkinson disease. What can you say to Steven about propranolol for shaking problems?
Case 4
You are working in a pharmacy situated in a commercial centre. A middle aged lady asks you about a preparation containing omega-3 fatty acids. She tells you that her parents both have Alzheimer's disease, and that her older sister also has ‘symptoms’. Can you recommend omega-3 fatty acids for prevention of Alzheimer's disease?
Case 5
You are working in a pharmacy situated in a commercial centre. A young mother is explaining that her 4-year-old daughter has a cold, cough with mucus, and asks if you can recommend any expectorant? What do you recommend?
National examples
Local or national practice guidelines can be very helpful if based on EBM sources. So, can you find and trust your local and nation recommendations and guidelines? Below we give examples from Sweden, England and China (the home countries of the authors) based on the client cases.
Case 1
In Sweden, there are local recommendations with background information available from drugs and therapeutics committees in all county councils, and updated every year. The one from Skåne is selected and presented below. National recommendations and guidelines are available from The National Board of Health and Welfare produced 2012 (selected see details below, table 2), SBU—Swedish Council on Health Technology Assessment 2003 and Medical Products Agency—Sweden 2007. Below we assess the sources based on box 2.
Recommendations and guidelines from Sweden
England and China
Within the UK NHS, there is national advice which translates into local or regional recommendations and guidelines (table 3). In China, there is also normally no local or regional recommendation, but expert opinions do play major roles for local areas (ie, eminence-based medicine).
Recommendations and guidelines from England and China
Suggested response: Based on the sources described above, the usability and trustworthiness differ between sources. Since Christina has a high risk for further fractures (measured eg, by FRAX), the treatment is less than optimal, and suggestions could be to first decrease risk factors and check swallowing problems. If no problem, suggest alendronate orally (discuss weekly or daily doses). If swallowing problems exist, suggest zoledronate injection once every year.
Cases 2–5
No local, regional or national recommendations or guidelines available in the three countries.
Summary of findings and discussion
As presented above, local and regional recommendations only exist in Sweden (for each county), not in England and China where national ones are applied. There seems to be low priorities especially to develop recommendations for self-care, over-the-counter (OTC) medications and remedies as presented in cases 2–5.
International examples
The Cochrane Library and Clinical Evidence are examples of international sources covering almost the whole of medicine. There are also numerous international associations or other groups of specialists covering different other areas of medicine and pharmacy. Finally, there are commercial organisations and companies providing web-based computer or App support. As described in table 1, there are benefits and drawbacks in using the different sources. Below, we tabulate information on the presented cases where we could not find reliable local and national sources, that is, cases 2–5.
Case 2
Searching Google for ‘gout prophylaxis allopurinol’ gave 1.2 million hits (20 February 2014). The first ‘About.com’, the second ‘Patient.co.uk’ (see selected details below) and the sixth ‘MDweb’ are all internet-based advice from commercial sources. Searching ‘medication’ in IPhone App Store (20 February 2014) gave 574 hits. Number 3, drugs.com medication guide, was the first related to selection of medication (see selected details below). This App links to an internet homepage with the same address.
There are international guidelines (in English) on gout prophylaxis focusing on allopurinol and other drugs from several sources. The European League Against Rheumatism (EULAR) have a guideline. The British Society for Rheumatology has a ‘Guideline for the management of gout’ but does not focus on prophylaxis, and it is from 2007. The American College of Rheumatology have ‘Guidelines for management of gout’ from 2012 (see selected details below).
The Cochrane Library has a protocol but no finalised review on ‘allopurinol for chronic gout’. In a review ‘febuxostat for treating chronic gout’ allopurinol is used as comparator (see selected details below).
Suggested response: Suggest withdrawal of allopurinol since the patient does not have gout and there is no evidence supporting asymptomatic high serum uric level treatment.
Case 3
Searching Google for ‘propranolol and Parkinson’s Disease’ gave 262 000 hits (20 February 2014).
The third hit was for the Cochrane Database of Systematic Reviews.13 This is a systematic review from 2003, of 4 studies, 72 patients, RCT, double-blind. The review states that there is lack of evidence for efficacy and safety. There was some evidence of a high frequency of bradycardia in normotensive elderly patients but that study was small. Additional hits were for the TRIP database (http://www.tripdatabase.com) who made a direct reference to Cochrane, and the Merck manuals database (http://www.merckmanuals.com) states that β-blockers may be used to reduce the severity of a tremor, without any specific reference. At ‘Patient.co.uk’ and ‘drugs.com’ described in case 2 there is no information, and the international movement disorders society (http://www.movementdisorders.org) also had no recommendation.
Suggested response: Since this is a question presented from a client in a pharmacy, a reasonable response could be the information from the Cochrane Review, that although based on very limited evidence, propranolol can be of value and can be tested especially if the patient also suffers from high blood pressure and does not suffer from asthma or other airway diseases. The client should also be informed to discuss this further with their physician.
Case 4
Searching Google for ‘omega 3 and Alzheimer’s Disease’ gave 2. 7 million hits (20 February 2014). Among the first 100 we found no international recommendations and guidelines or clear recommendations from databases and Apps as presented in case 2.
In the Cochrane Database of Systematic Reviews there is a review from 201212 on Omega 3 fatty acid for the prevention of cognitive decline and dementia . The researchers conclude that the longer-term effects of omega-3 fatty acids on cognitive decline and dementia need to be explored further, particularly in people with low dietary intake. In the meantime, they stress other potential health benefits. ‘Fish is an important part of a healthy diet and we would still support the recommendation to eat two portions a week, including one portion of oily fish’.
Suggested response: This is a question from a middle aged lady presented at a pharmacy, and a reasonable response could be that there is limited evidence on the benefit and that a normal healthy diet, including fish and also oily fish, is probably a better choice.
Case 5
Searching Google for ‘cold and expectorant’ gave 2 800 000 hits (February 2014) with the top 100 only focusing on sales and identification of preparations. At ‘Patient.co.uk’ and ‘drugs.com’ described in case 2 there is no recommendation. There are 31 Cochrane Reviews on the topic ‘Common cold & cough’ including almost all of the potential remedies you can imagine. Not focused direct on cough and expectorant, but one from 2012 on ‘OTC medications for acute cough in children and adults in ambulatory settings’ stated that no studies using expectorants met their inclusion criteria. Their conclusion was ‘there is no good evidence for or against the effectiveness of OTC medicines in acute cough. The results of this review have to be interpreted with caution due to differences in study characteristics and quality. Studies often showed conflicting results with uncertainty regarding clinical relevance. Higher quality evidence is needed to determine the effectiveness of self care treatments for acute cough.’
Suggested response: The response must be based on the results and discussion from the Cochrane database. There is no evidence to support the benefit of expectorants or any other preparation.
Summary of findings and discussion
As presented, international recommendations and guidelines differ largely in usability and reliability (tables 4 and 5). The Cochrane Database of Systematic Reviews and also expert organisations can generally be trusted but need some effort to find and read, although the abstract and conclusion is often what is needed to respond to a question. More commercial internet and smartphone applications (Apps) are easy to find but are less reliable. Especially Apps with no counterpart internet application can be very difficult to assess for reliability, so beware!
International recommendations and guidelines
International sources for individualisation of medication
The number of Apps for health-related information is rapidly growing, so is the number of users, including among healthcare professionals.16 Recently, Mosa16 studied 57 Apps for healthcare professionals focusing on disease diagnosis (21), drug reference (6), medical calculators (8), literature search (6), clinical communication (3), Hospital Information System client applications (4), medical training (2) and general healthcare applications (7). The disease diagnosis, drug reference, and medical calculator applications were reported as most useful. Some of the content can be of value, but for selection of drugs, they cannot be trusted.
Sources for individualisation of medication
As presented in box 1, individualisation of a selected medication involves selecting the preferred route for administration, and a correct dose based on all important aspects for a patient is presented in box 4. It also includes follow-up to be able to further individualise the dose.
The aspects for individualisation of medication, as described in box 4, are based on professional knowledge and competencies including topics like pharmacodynamics, pharmacokinetics and medicines technologies. No other profession would be able to support the patient or client and healthcare better based on professional education and skills. Sometimes the pharmacist also has to take responsibility to find alternative preparations or even prepare the medication from scratch. The information needed can be technical, clinical or both as described in the cases presented below.
Important aspect for patient medication individualisation
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Proper route and administration form
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Oral
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Immediate or slow release
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Swallowing problem (Crush tablets, prepare suspension, NG tubes etc.)
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Intravenous
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Bolus, slow injection, infusion
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Incompatibilities in solution, y-site
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Subcutaneous and intramuscular
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Length of needle
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Other routes
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Proper dose
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Drug–disease interaction
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Drug–drug interaction
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Drug–food interaction
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Therapeutic Drug Monitoring (TDM) and dose calculation
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Case 6. You fill a prescription for Clopidogrel tablet 75 mg for Rhonda, female 63 years old, at your pharmacy. She also has a new prescription for omeprazol 20 mg and asks if she can take those simultaneously.
Case 7. You are working as a consultant pharmacist at a healthcare centre. Nicolas 25 years with epilepsy is prescribed carbamazepine tablets 400 mg three times a day. Due to problems with compliance, he and the responsible physician ask you if a dose schedule twice a day is possible.
Case 6
Table 5 presents important and useful sources for individualisation of Rhonda's medications.
Suggested response: The three sources all state the drug combinations to be inappropriate and as a pharmacist you must act, especially since the patient has sought your advice. Contact with the patient and the physician is needed to change the prescriptions for clopidogrel (to aspirin) or omeprazole (to pantoprazole or lansoprazole).
Case 7
Tegretol is too old to be included with an SPC at the EMA homepage. In Sweden23 UK and China24 a nationally approved SPC is available. The maintenance dose with Tegretol is stated to be 400 mg 2–3 times daily. Tegretol depot is an alternative with a maintenance dose of 200 mg 2–3 tablets, or 400 mg 1½ tablet twice a day. Also it is stated that the bioavailability for the depot tablets are 10–20% lower. Based on this, a suggestion to change to Tegretol depot tablets 400 mg 1½ tablets, or 200 mg 3 tablets twice a day seems realistic with follow-up on effects, and maybe a concentrated measure before and 1 week after the change.
Summary of findings and discussion
As presented in the cases above, similar information can be found in the SPC from EMA/FDA, national approved SPC and also on the Micromedex database. However, when more detailed information is needed, the Micromedex database is of great value as described in table 6.
Information normally available from SPC and the Micromedex database
A CDS in the COE or pharmacy system could be a very useable and integrated system to support you directly. Since there normally are many different systems in each country from various providers it is impossible for us to review if they are usable and can be trusted. Therefore, you have to ask the provider to explain each source used in the system, and how the system manages the information. One way could be to prepare a couple of cases and compare the information given in the CDS with the information from the SPC or other reliable sources
Sources for follow-up on medication benefits and harms
Sources for questions as described in box 1 for follow-up on medication benefits and harms can be found from various sources including those discussed for selection and individualisation. Follow-up on effects and adverse effects depends on pharmacodynamics and pharmacokinetics, what, how and when to follow-up is important. Documentation, communication, information, patient's adherence and so on, are also other important factors. Regulatory aspects can be found in the SPC, but local, regional and national aspects for optimal delivery of care are very important. This is discussed in more detail in a later chapter.
Your evidence-based information sources today and tomorrow
As a pharmacist, you have to respond to your clients’ needs in a professional way based on the philosophy and responsibilities of pharmaceutical care4 and adapt the best available evidence to the client.3 Finding your own evidence-based resources and systematically using these will help you to build a framework for your own professional development. It is also important that each pharmacist collaborates with other local or regional pharmacists and they learn from each other. If possible, it could be helpful to agree on what sources to use on each occasion and to collaborate in building information sources that can be trusted for practicing evidence-based pharmacy.
Footnotes
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Phil Wiffen is editor-in-chief of EJHP and also teaches methodology for EBM and systematic reviews.
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Tommy Eriksson is Professor in Clinical Pharmacy, employed at Lund University and Malmö University in Sweden.
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Hao Lu is a clinical pharmacist based at the Beijing United Family Hospital in China.
Footnotes
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Competing interests None.
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Provenance and peer review Commissioned; internally peer reviewed.