Report on Technical Updateof the Essential Medicines Library

Katharine Jones, Anna Ridge, Derval Harte, Effective Health Care Research Programme, Liverpool School of Tropical Medicine, U.K.

July 2006

Background

The World Health Organization (WHO) is linking policy to best available evidence. Between May and July 2006 we carried out a technical update of the Essential Medicines Library (EMLib) on http://mednet3.who.int/EMLib/DiseaseTreatments/Medicines.aspx.

Under a grant from WHO we collaborated with Sue Hill from the Medicines Policy and Standards Department to identify high quality, recent evidence relevant to the selection and use of the 298 medicines in the library (vaccines excluded from update), and to check the on-line profile for each medicine as follows:

Section Formulation Anatomical Therapeutic Chemical (ATC) classification code Drug status Disease/Indication Rationale for use Guidelines

Methods

See Annex 1. Methods were drafted following an exploratory visit to Geneva in May. During the project we encountered several issues as detailed below.

Issues identified

SectionSome inconsistencies in section existed between the EMLib and the WHO Model list as the library is yet to be updated in line with the changes made between the 13th and 14th editions of the Model list.

Formulation A significant number of WHO formulations were not listed in any of the three international formularies consulted. For some medicines formulations which appeared more appropriate in view of the recommended dosage schedule were not included in the library. See Annex 2 for full details.ATC codeSome drugs had no code listed on the ATC website e.g. aluminium diacetate.

Some codes were incorrect e.g. The cephalosporins such as ceftriaxone EMLib J01DA13 ATC code website J01DD04.

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Combination drugs were a particular problem with few codes listed on the ATC website e.g. Mifepristone-misoprostol codes only available for each component drug.

Drug statusThis section was cross checked with the “Comparative table of core and complementary medicines on the WHO Essential Medicines List from 1977- 2005” As with several WHO documents consulted during the project this spreadsheet contained a key using numbers and letters but no explanation of what these stood for. Some drugs featured on both the core and complementary list for different indications.

Disease/IndicationThe WHO applications website and technical reports provide information on the selection and use of drugs on the model list.

a) Applications Searching for applications was time consuming due to the complexity of the search required for each medicine as detailed in Annex 3. Several documents published on this site contained tables with no clear headings and abbreviations we were unable to interpret.

b) Technical reportsMost technical reports on the WHO website are scanned documents on which Microsoft Office is unable to search. Each report is over 60 pages long and so hand searching was not an option. Using “PDF creator” we were able to convert these files into word documents and search electronically. The main component of most the reports was a reproduction of the model list with only the last tenth of the document provided any useful information on the selection and use of specific drugs. Technical reports published since the introduction of the application process in 2002 were notably more informative.

For some drugs we were unable to find any documentation to support the selection and use of a drug for the indications stated on the EMLib. This was a particular problem for antibiotics included in the library, many of which had multiple indications with some no longer clinically relevant. Following discussion with Sue Hill we restricted the indications for this group of drugs to the most important clinical conditions and drafted a generic statement for all antibiotics “for use in the treatment of infections with susceptible organisms including…(important clinical conditions). Local antimicrobial resistance patterns need to be taken into account”

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Rationale for useThis section was generally used to state the date added to the list and whether a medicine had a square box used to indicate similar clinical performance within a pharmacological class. Where a square box was added we listed comparable alternatives if these were stated in the relevant technical report.

WHO guidelines We searched four databases for WHO global guidelines relevant to the selection and use of each drug as detailed below. Where no WHO guideline was available we searched a national guideline clearing house. This was by far the most time consuming element of the update due to issues with both guideline documents and databases as summarised below and in Annex 4.

1. Documents No title or explanation regarding the context of the document for some pdfs No publication date available in some WHO documents Page indexing system for some hard copy documents was

inadequate for our needs e.g. Guidelines for the treatment of malaria

2. Databases

a) WHO Library and Information Networks for Knowledge Database (WHOLIS) Search engine lacked sufficient sensitivity for our

requirements. Ability to order and restrict results by publication date greatly

reduced time taken to identify most relevant reference. Labelling of references good and included publication date

b) WHO website Search engine lacked sufficient specificity for our requirements High number of results and inability to order or restrict by

publication date or relevance made identifying relevant results for some drugs impractical.

Labelling of references unclear and often missing publication date necessitating inspection of full document to establish relevance.

Some full documents did not include publication date.

c) WHO Health Topics site Clear categorisation by disease indication made search easy Very few documents available via this site

d) Google Search engine sufficiently sensitive Results appeared to generally be ordered by relevance

allowing rapid identification of the most relevant document. For some drugs using this search engine was the fastest and

most consistent method of identifying relevant guidelines. References generally clearly labelled although some missing

publication date

e) Guideline Clearing House

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Search engine sufficiently sensitive and specific Labelling of results clear Guidelines produced by institutions in the U.K., U.S.A. and

Australia so may not be relevant to low and middle income countries

EvidenceWe were able to identify a relevant Cochrane review for the majority of drugs on the list using the Centre for Reviews and Dissemination Database (see Annex 5 for those drugs without a review). For those medicines without a Cochrane review we quoted other forms of randomised evidence where available.

Library presentation

At present references in the on-line version of the library are not labelled or divided according to type i.e. technical reports, WHO guideline, Cochrane review etc.

Time taken

Total of 540hrs for three people to complete technical update of profiles for all medicines (does not exploratory visit to Geneva)

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Summary

Accessibility of information WHO documents

No publication date stated in some WHO publications No internal key available in several WHO reference documents Page indexing for hard copies of some guidelines did not meet our needs

WHO website Scanned technical reports made electronic searching impossible Searching for applications was complex and time consuming WHOILS search engine lacked sensitivity although ordering and labelling of

results allowed rapid identification of the most relevant document. WHO website search engine lacked specificity and lack of capacity to order

or restrict results plus poor labelling of references made identifying the most relevant document time consuming.

EMLib The profile of most medicines in the library now includes a reference to a

relevant Cochrane review.

Proposals for change

Improvement in search engine capacity, labelling of search results and indexing of WHO documents would greatly increase the accessibility of information.

An on-line inventory of WHO guidelines would be useful. An alternative reference source for WHO formulations is required. Division and labelling of library references by document type would be

helpful. Qualitative research to gain feedback from users of the library would be

informative.

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ANNEX 1

Methods for technical update of the Essential Medicines Library

Background

The task is to identify reliable, up-to-date evidence relevant to each of medicines included in the library on http://mednet3.who.int/EMLib/DiseaseTreatments/Medicines.aspx and check the entry for each medicine as follows:

Section Formulation Anatomical Therapeutic Chemical (ATC) classification code Drug status Disease/Indication Rationale for use Guidelines

In our experience updating the library by drug sections rather than in alphabetical order is more efficient as there is documentation overlap between drugs within each section. A separate word file for each drug profile with comments inserted allows queries to be flagged.

1. Section

Check correct by using edit and search function on "14th Model" list pdf and use NEXT function to locate all mentions of drug.

2. Formulation

Search any of the on-line international formularies below to cross check the WHO formulation:-

BNF http://www.bnf.org/bnf/Australian Medicines Handbook http://www.amh.net.au/ (subscription only)MIMS Asia http://asia.mims.com/ref/online.htm

If not in any of the above try searching Google!NB Martindale: The complete drug reference contains no details on formulation.

Injectable formulations should only be on the list if absolutely necessary. Please flag if you think an injectable formulation is surplus to requirements.Please keep a list of any drugs not listed in the BNF or MIM, or where there are discrepancies between the listing in the WHO formulary and the references.

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3. ATC code

Cross check with ATC codes website www.whocc.no/atcddd/indexdatabase/index.php . . Please flag if the code is unclear or appears incorrect for the indication.

4. Drug status

Check core/complimentary status from “Comparative table of core and complementary medicines on the WHO Essential Medicines List from 1977- 2005” spreadsheet. The default status for all drugs is core and drugs should only be moved to the complimentary list with good reason (special equipment required etc.). Please flag any drugs whose status appears incorrect. Where a square box has been added please state the year when this occurred and any comparable alternatives as specified in the technical reports so that countries can choose the drug they can get hold of the cheapest and easiest.

5. Disease/Indication

Search WHO applications and technical reports as below.

For drugs with multiple indications chose the most important 2 or 3 and only search and include evidence relevant to these conditions.

For antibiotics include a generic statement “for use in the treatment of infections with susceptible organisms including…. Local antimicrobial resistance patterns need to be taken into account”.

State any information found and flag any inconsistencies between statements in these documents and available evidence. Any important contra-indications should be included in this section but not prescribing information as this is outside the remit of the site.

6. Rationale for use

If no available evidence then just state the date added to the list. For drugs which are known to be widely misused it may be appropriate to quote the evidence.

7. Date added

Check this in the “Comparative table of core and complementary medicines on the WHO Essential Medicines List from 1977- 2005” spreadsheet.

8. Applications

Search for applications from 12th, 13th and 14th expert committee agendas via the applications website listed below using the search process described in annex 3. If the application contains relevant information then no need to quote anything else. If no relevant information available in any of the application documents but the drug is listed then still quote relevant document but flag that it is not a useful reference.http://www.who.int/medicines/services/expertcommittees/essentialmedicines/exp_com_essmed_meetings/en/index.html

9. Technical reports

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Check spreadsheet for year drug added to Essential Drug list.

Search Technical reports from year added to list using find and edit from Technical reports word files as those on website are scanned documents and therefore edit and find function does not work. Be careful to click on the main text of the word document before using the edit and find function as otherwise the function will only search the text box highlighted.

Only quote the report in which the drug was added or any where there was a change in the status of the drug or relevant information is available.

TRS and corresponding years listed below:

TR 722 – 1985TR 770 – 1988TR 796 – 1990TR 825 – 1992TR 850 – 1995TR 867 – 1997

TR 882 - 1998TR 895 – 2000TR 914 – 2003TR 920 – 2004TR 933 – 2005

NB draft technical report 933 is available as a pdf via the applications website www.who.int/medicines/services/expertcommittees/essentialmedicines/exp_com_essmed_meetings/en/index.html under 14th expert committee and unedited expert committee report.

10. WHO guidelines

For each drug please use the following search strategy

a) WHOILS http://dosei.who.int/uhtbin/cgisirsi/mJ6ddjOETd/0/49

Use the search strategy:-

“drug name” +/- “guideline/s”“drug group” +/- “guideline/s”“disease” +/- “guideline/s”

For drugs with multiple indications only search and include evidence relevant to the most important 2 or 3 indications as specified in Disease/Indication section.

b) Search the main WHO website http://www.who.int/en/ using the same search strategy as in a)

c) Search the health topic site http://www.who.int/topics/en/ using the same search strategy as in a)c) Search google using same search strategy as in a) but also including the phrase “World Health Organization”

d) Search anywhere else you can think of!

Please insert a comment detailing which method led you to the guideline and any info which you think may be useful feedback.

11. Other guidelines

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If no WHO Guideline found search guideline clearing house www.guideline.gov/ and list as a hyperlink.

12. Evidence

Search the Database of Abstracts of Reviews of Effectiveness via the link below for relevant evidence. If a Cochrane review is available this is sufficient. Keep a list of drugs with no Cochrane review and quote other evidence where available. Include all reviews whether supportive or not but insert comment if not supportive.http://144.32.150.197/scripts/WEBC.EXE/NHSCRD/start

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ANNEX 2

Formulation issues

Drug name Formulation on 14th

Model ListProblem with current

formulationAluminium diacetate Solution 13 % Unable to find - BNF and

mims AsiaAluminium hydroxide Formulation

Oral suspension 320 mg/5mL

Not found. A 200mg/ml oral suspension is available

Amidotrizoate Injection 120-420mg iodine (as sodium or meglumine salt)/mL in 20 mL ampoule

Need to check formulation with manufacturer

Azithromycin Oral suspension 200 mg/5 mL

Unable to cross reference formulation

Barium sulphate Aqueous suspension Unable to find formulation

Biperiden Injection 5 mg/mL in 1-mL ampoule

Is injection formulation required? Not found in BNF/mims Asia. Review for possible deletion?

Calamine lotion Lotion BNF: lotion containing calamine 15% zinc oxide 5% glycerol 5% betonite 3%, sodium citrate 0.5%, liquefied phenol 0.5%, in freshly boiled and cooled purified water

Carbimazapine Tablets 100mg, 200mg Suggest review for addition of 400mg formulation, in view of max dose of 1.2g – 2g daily in epilepsy

Charcoal, activated Powder for oral suspension No formulation given. Formulations available include 25g and 50g packs

Chloroquine 100mg tablet and 150mg as phosphateInjection

Unable to find formulationIs injection formulation still appropriate for list?

Chlorine base compound

Powder (0.1% available chlorine) for solution

Cannot find formulation

Chloroxylenol Solution 4.8% Cannot find formulationChlorpromazine Tablet 100 mg

(hydrochloride) Initial starting dose is 25 mg TID. Should further tablet formulations be added? (10 mg, 25 mg and 50 mg formulations are available)

Clomipramine Capsules 10 mg, 25 mg Should 50 mg capsule be included? (upper dosage level for OCD can reach 250 mg)

Coal tar Solution 5 % Other concentrations found, but not 5 %

Cyclophoshamide Tablet 25 mg 50 mg, 100 mg and 200 mg

Drug name Formulation on 14th

Model ListProblem with current

formulationtablets are available. 25 mg not found

Cycloserine Capsule or tablet 250 mg Tablet formulation not foundDaunorubicin Powder for injection 50 mg 20 mg found. 50 mg available

in liposomal form, but not injection

Diazepam 5 mg/mL in 2-mL amp. (rectal or IV)

In BNF 5 mg or 10 mg rectal solution

Didanosine (ddl) Buffered powder for oral solution 100 mg, 167 mg, 250 mg

Unable to find

Diethycarbamazine Tablet 50 mg, 100 mg 100 mg tablet not found (only 50 mg and 300 mg)

Enalapril Tablet 2.5 mg Starting dose is 5 mg. 2.5 mg formulation no longer appropriate?

Epinephrine (adrenaline)

1mg (as hydrochloride)/ml in ampoule, Section 12.02.00.00 (for use in cardio-pulmonary resuscitation) which is equivalent to 1/1000

The IV dose should be 1/10,000 (100mcg/ml). Incorrect formulation listed. Need to review

Ergocalciferol Capsule or tablet 1.25 mg (50000 IU), Oral solution 250 micrograms/mL (10000 IU/mL)

Can only find 250 microgram dose as a capsule. No oral solution found

Ergometrine Injection 200 micrograms in 1-mL amp.

Only formulation found is 500 micrograms

Ethionamide Tablet 125 mg, 250 mg Unable to find 125 mg tabletFlucytosine Capsule 250mg; infusion

2.5g/250mlCapsule cannot be found. BNF states that tablet can be ordered on a named patient basis from Bell and Croyden

Fluorouracil Ointment 5% Only cream found in BNF/mims Asia

Folic acid Tablet 1mg, 5mg Cannot find 1mg tabletGlutaral Solution 2%; Cannot find in any formularyHeparin sodium Injection 1,000 IU/ml,

5,000IU/ml, 20,000IU/ml in 1 ml amp

20,000IU/ml does not appear to be available. Usual formulation available is 25,000IU/ml

Hydrocortisone Suppository 25mg (acetate); Retention enema (section: 17.03.00.00)

This formulation cannot be found

Idoxuridine Solution,( eye drops) 0.1%; eye ointment 0.2%

0.1% eye solution found (Indonesia) Cannot find eye ointment

Indinivir (IDV) Capsule 200mg, 333mg, 400mg (as sulphate)

Only 200mg and 400mg formulations appear to be available

Insulin (intermediate-acting)

40IU/ml in 10 ml vial, 100IU/ml in 10 ml vial, (as

There do not seem to be 40 IU/ml vials

Drug name Formulation on 14th

Model ListProblem with current

formulationcompound insulin zinc suspension or isophane insulin)

Insulin (soluble) Injection, 40IU/ml in 10 ml vial, 100IU/ml in 10 ml vial

There do not seem to be 40 IU/ml vials

Iodine Iodized oil, 1 ml (480 mg iodine) in ampoule (oral or injectable); 0.57 ml (308 mg iodine) in dispenser bottle; capsule 200mg.

These formulations cannot be found (Lugol’s soln available, this is 130mg/ml iodine)

Iohexol Injection 140-350mg iodine/ml in 5 ml, 10ml and 20ml ampoule

Like other radiocontrast media this formulation cannot be found

Iopanoic acid Tablet, 500mg Like other radiocontrast media this formulation cannot be found

Isoniazid + ethambutol

Tablet, 150mg + 400mg No formulation can be found

Ivermectin Scored tablet, 3mg, 6mg No formulation can be found

Levamisole Tablet 50 mg, 150 mg Unable to find 150 mg tablet

Lidocaine Injection for spinal anaesthesia, 5% (hydrochloride) in 2-ml ampoule to be mixed with 7.5% glucose solution

Unable to find

Neomycin sulfate + bacitracin

Ointment 5 mg neomycin sulphate + 500 IU bacitracin zinc/g

Cannot find this formulation. Neomycin sulfate 3,300 units, bacitracin zinc 250 units, l-cysteine 2 mg, glycine 10 mg, dl-threonine 1 mg per g; cream and powder(from BNF + emims)

Nicotinamide Tablet 50 mg Unable to cross reference WHO formulation

Nifurtimox Tablet 30 mg 120 mg 250 mg

Unable to cross referenceWHO formulation

Oxamniquine Capsule 250 mg, Syrup 250 mg/5 mL

Unable to cross reference WHO formulation

Pentamidine Tablet 200 mg 300 mg Unable to find tablet formulation.

Potassium chloride Powder for oral solution, potassium chloride 1.5g

Unable to find formulation for powder

Potassium ferric hexacyanoferrate (II) 2H20 (Prussian blue)

Powder for oral administration

Unable to cross reference WHO formulation

Potassium iodide 1 g/mL (saturated solution) Unable to find

Praziquantel Tablet 150 mg Unable to find

Drug name Formulation on 14th

Model ListProblem with current

formulation

Procaine benzylpenicillin

Injection (powder for solution) 1g vial (1 million IU) 3g vial (3 million IU)

Unable to find

Propranolol Tablet 20mg, 40mg (Hydrochloride)

BNF/mims Asia - 20 mg tablet not listed. 10 mg is available

Propyliodone Oily suspension 500-600 mg/mL in 20-mL ampoule

Unable to cross reference formulation

Pyrazinamide Tablet 400 mg BNF/mims Asia - 500 mg tablets only. WHO formulary states 500mg not included in model list

Pyridostigmine Injection 1 mg in 1-mL ampoule

Not found

Rabies immunoglobulin

Injection 150 IU/mL in 2-mL or 10-mL vial

Unable to find

Rifampicin Capsule or tablet 150 mg, 300 mg

Cannot cross reference tablet formulation

Rifampicin + isoniazid 60 mg + 30 mg, 150 mg + 75 mg, 60 mg + 60 mg (For intermittent use three times weekly) 150 mg + 150 mg (For intermittent use three times weekly)

Unable to cross reference – BNF and mims Asia

Rifampicin + isoniazid + pyrazinamide

Tablet 60 mg + 30 mg + 150 mg, 150 mg + 150 mg + 150 mg (for intermittent use three times weekly)

Unable to cross reference

Salbutamol Injection 50 micrograms (as sulfate)/mL in 5-mL ampoule

Hong Kong and Indonesia have a 500 mcg/1 mL in 1-mL amp.

Salicylic acid Solution 5 % Unable to cross reference - BNF and mims Asia

Sodium hydrogen carbonate

Injectable solution, 1.4% isotonic (equivalent to Na+ 167 mmol/l, HCO3- 167 mmol/l) 8.4% solution in 10-ml ampoule (equivalent to Na+ 1000 mmol/l, HCO3-1000 mmol/l)

Unable to cross reference injectable solution 1.4 %isotonic and mmol/l for both formulations (8.4% solution in 10-ml ampoule is available)

Sodium nitrite Injection 30 mg/mL in 10-mL ampoule

Cannot cross reference ampoule size.

Sodium thiosulfate Cutaneous solution 15 % Unable to cross reference

Stavudine (d4T) Oral solution (powder for reconstitution) 5 mg/5 mL

BNF and mims Asia have 1mg/1 mL oral solution

Suramin sodium Powder for injection 1 g in Unable to find formulation

Drug name Formulation on 14th

Model ListProblem with current

formulationvial

Suxamethonium Powder for injection (chloride) in vial

Unable to find formulation

Testosterone Injection (oily) 200 mg (enantate) in 1-mL vial

BNF and mims Asia have 250 mg in 1-mL amp.

Triclabendazole Tablet 250 mg Unable to find formulation

Urea Cream or ointment 10 % Cannot find ointment formulation

Vancomycin Powder for injection 250 mg (as hydrochloride) in vial

Unable to find 250 mg formulation. BNF and mims Asia have 500 mg and 1 g formulations

Zinc sulfate Tablet or syrup in 10 mg per unit dosage form

Are these formulations available yet?

*Resources used for cross referencing included the British National Formulary, mims online (Asia) and the Australian Medicines Handbook

ANNEX 3

Methods for searching the applications website

12 th Application

First step

Agendas and Procedure

then

Agenda for the Expert Committee meeting 15-19 April 2002

then

5. Applications for additions or deletions AND 7. Review of summary statements on reasons for inclusion and underlying

evidence

Second step

Meeting documents

Third step (HIV and A-L only)

Notes on the inclusion of new items on the Model ListAND Summary of Recommendations by the Expert Committee on the Selection and

Use of Essential Medicines

13th Application

Step one

Draft agenda (version, 18 February 2003)

Then

2. Applications for addition

AND   3. Application for deletion

AND 4. Application for addition of information

AND 5. Application for change

AND 6. Fast track deletion

AND 7. Review of Core and Complementary Listing

AND   8. Review of use of Square Box Symbol

AND 9. Review of section 12.3 Antihypertensive Medicines

14th Application

Step one

Draft agenda

then

All sections except “Update on current activities”

Step two

Unedited Expert Committee Report

Step three

Summary Expert Committee Recommendations NB link not working

ANNEX 4

Identifying WHO guidelines

We used searched the following four databases in an attempt to identify WHO guidelines relevant to the selection and use of each drug:

a) WHO Library and Information Networks for Knowledge Database (WHOLIS)b) WHO main websitec) WHO health topics websited) Google

This proved to be a complex and time consuming process. The example given below of the anti-malarial artesunate highlights specific problems with each of the four databases and illustrates how difficult it was to identify a recently published WHO global guideline “Guidelines for the treatment of malaria” using the search strategy described in annex 1.

a) WHOLIS

a) WHOLIS (cont)

“artesunate” and “guideline” produced no matches

Drop down boxes containing default terms do not appear to enhance search capacity

Capacity to sort results by various characteristics greatly reduced time spent identifying most relevant reference

Unclear if searching title or full document. Some results not logical for

“artesunate” and “guidelines” produced no matches

a) WHOLIS (cont)

“anti-malarial” and “guideline” produced no matches

“anti-malarial” and “guidelines” produced no matches

a) WHOLIS (cont)

“malaria” and “guideline” produced no matches

“malaria” and “guidelines” ranked “Guidelines for the treatment of malaria” 4th out of 54 matches.

b) WHO website

Full title of document clearly stated

Publication date stated in reference label

Full text link available

Details of publication location available

Search engine looks for complete word or phrase c.f. Google

Often produced unmanageable number of results

i. Standard search

ii. Advanced search

Context of document often unclear from reference label

No clear pattern to the information provided here and often not helpful

Often no publication date in reference required full document to be opened and searched. Some full documents had no record of publication date

Allows specification of where the search terms occur in the page

No capacity to restrict or order search results by publication date or relevance

b) WHO website

“artesunate” and “guideline” produced 126 matches of which none corresponded to “Guidelines for the treatment of malaria”

“artesunate” and “guidelines” ranked “Guidelines for the treatment of malaria” 1st out of 665 matches.

b) WHO website (cont)

Full title of document often unclear from reference heading

No publication date stated in most

Unclear what this statement refers to

No publication date in reference

“anti-malarial” and “guideline” produced 317 matches of which none of the first 100 corresponded to “Guidelines for the treatment of malaria”

“anti-malarial” and “guidelines” ranked “Guidelines for the treatment of malaria” 4th out of 2,110 matches.

b) WHO website (cont)

“malaria” and “guideline” produced 1660 matches of which none of the first 100 corresponded to “Guidelines for the treatment of malaria”

“malaria” and “guidelines” ranked “Guidelines for the treatment of malaria” 22nd out of 11,000 matches.

c) WHO Health Topics site

The pages on this site contain links to WHO projects, initiatives, activities, information products, and contacts, organized by health and development topics.

“Guidelines for the treatment of malaria” easily accessed via this site under publications.

d) Google

Clear categorisation of site by disease indication

Title and publication date of guideline clearly stated

“World Health Organization”, “artesunate” and “guideline” ranked “Guidelines for the treatment of malaria” 65th out of 23,200 matches

“World Health Organization”, “artesunate” and “guidelines” ranked “Guidelines for the treatment of malaria” 49th out of 22,800 matches

No publication date specified

No publication date specified

d) Google (cont)

“World Health Organization”, “anti-malarial” and “guideline” ranked “Guidelines for the treatment of malaria” 1st out of 85,600 matches.

“World Health Organization”, “anti-malarial” and “guidelines” ranked “Guidelines for the treatment of malaria” 1st out of 84,000 matches.

No publication date specified

No publication date specified

d) Google (cont)

“World Health Organization”, “malaria” and “guideline” produced 2,910,000 matches of which “Guidelines for the treatment of malaria” was ranked 1st. Title of document clear from reference but no publication date specified.

“World Health Organization”, “malaria” and “guidelines” produced 2,830,000 matches of which “Guidelines for the treatment of malaria” was ranked 1st. Title of document clear from reference but no publication date specified.

No publication date specified

No publication date specified

Summary of issues in searching for relevant WHO Guidelines

WHO Library and Information Networks for Knowledge Database (WHOLIS)

Search engine lacked sufficient sensitivity for our requirements. Ability to order and restrict results by publication date greatly reduced time

taken to identify most relevant reference. Labelling of references good and included publication date

WHO website

Search engine lacked sufficient specificity for our requirements High number of results and inability to order or restrict by publication date

or relevance made identifying relevant results for some drugs impractical. Labelling of references unclear and often missing publication date

necessitating inspection of full document to establish relevance. Some full documents did not include publication date.

WHO Health Topics site

Clear categorisation by disease indication made search easy Very few documents available via this site

Google

Search engine sufficiently sensitive Results appeared to generally be ordered by relevance allowing rapid

identification of the most relevant document. For some drugs using this search engine was the fastest and most consistent

method of identifying relevant guidelines. References generally clearly labelled although some missing publication date

ANNEX 5

No relevant Cochrane review

1. Abacavir (protocol published)2. Aminosalicylic acid3. Amlodipine4. Aluminium diacetate5. Amidotrizoate6. Ascorbic acid7. Asparaginase8. Atropine9. Anti-tetwnus immunoglobulin10. Barium Sulfate11. Benzoic acid and salicylic acid12. Benzoyl peroxide13. Benzyl benzoate14. Calamine Lotion15. Calcium Gluconate16. Capreomycin17. Ceftazadime in treatment of Pseudomonas Aeruginosa18. Chlorhexidine19. Chlorine based compound20. Chlormethine21. Chloroxylenol22. Clofazamine23. Clomipramine in treatment of obsessive compulsive disorders24. Coal Tar25. Condoms: no review regarding efficacy as contraceptive26. Cycloserine (only review regarding treatment of MDR TB is prophylaxis of

those at risk)27. Cytarabine28. Dactinomycin29. Dapsone30. Daunorubicin31. Dexamethasone in treatment of allergies and anaphylaxis32. Diethylcarbamazine (only a review of DEC fortified salt)

33. Diloxanide34. Dimercaprol35. Diptheria anti-toxin36. Eflonithine37. Erythromycin (only 1 review , treatment of whooping cough)38. Ethanol39. Ethinylestradiol40. Ethinylestradiol & levonorgestrol ( only 1 review; effect on weight gain)41. Ethinylestradiol & norethisterone42. Etopooside43. Ethionamide44. Flucytosine (protocol published “Treatment of acute cryptococcal meningitis

in HIV-infected adults in resource-limited settings”)45. Fluorescein46. Glucose : Only 1 review with referance to treatment of Hyperkalaemia47. Glceryl trinitrate48. Glutaral49. Hydrocortisone (No reviews with regard to palliative care, adjunct in cancer

treatment, anaphylaxis. One protocol for rectal use in ulcerative colitis)50. Intraperitoneal dialysis solution51. Iohexol52. Lopinavir with ritonavir53. Medroxyprogesterone acetate54. Meglumine antimoniate (protocols published)55. Melarsoprol (RCT only)56. Mercaptopurine57. Methotrexate (Section: 08.02.00.00)58. Methylrosanilinium chloride (gentian violet)59. Methylthioninium chloride (methylene blue)60. Morphine (Section 01.03.00.00)61. Neostigmine62. Niclosamide63. Nicotinamide64. Nitrous oxide65. Norethisterone enantate66. Paracetamol (2nd)67. Penacillamine

68. Pentamine (all sections)69. Podophyllum resin70. Polyvidone iodine71. Potassium chloride72. Potassium ferric hexacyanoferrate73. Potassium iodide74. Potassium permanganate75. Primaquine (protocol published 2003)76. Procainamide77. Propyliodone78. Protamine sulfate79. Pyrazinamide80. Pyridostigmine81. Procarbazine82. Pyrimethamine83. Quinidine84. Rabies immunoglobulin85. Riboflavin86. Ritonavir (protocol)87. Saquinavir88. Selenium sulphide89. Silver sulfadiazine90. Sodium calcium edentate91. Sodium lactate (compound solution)92. Sodium nitrite93. Sodium nitroprusside94. Sodium thiosulfate95. Spironolactone96. Sulfadiazine97. Suramin sodium98. Testosterone99. Tetracaine100. Thiopental101. Timolol102. Triclabendazole103. Tropicamide104. Urea

105. Vancomycin106. Vecuronium107. Verapamil108. Water for injection