Wound Healing Pharmaceuticals: What the EBM Tells Us Robert G. Smith DPM., MSc., R.Ph., C.Ped PharmCon2008 Pharmcon is accredited by the Accreditation

Wound Healing Wound Healing Pharmaceuticals: What the Pharmaceuticals: What the

EBM Tells UsEBM Tells UsRobert G. Smith DPM., MSc., R.Ph., C.PedRobert G. Smith DPM., MSc., R.Ph., C.Ped

PharmConPharmCon20082008

Pharmcon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education

Learning ObjectivesLearning Objectives

Appreciate the selection of the most appropriate Appreciate the selection of the most appropriate wound healing product with regard to a wound healing product with regard to a presenting wound type as supported by relevant presenting wound type as supported by relevant clinical evidence based data.clinical evidence based data.Develop a wound care product formulary for use Develop a wound care product formulary for use in a clinical practice supported by available in a clinical practice supported by available evidence based medicine.evidence based medicine.Appreciate the clinical data regarding medicinal Appreciate the clinical data regarding medicinal alternative wound care products as found in the alternative wound care products as found in the literatureliterature

Prevalence of Diabetes MellitusPrevalence of Diabetes Mellitus

Total: 20.8 million people—7 percent of the population—have diabetes.

Diagnosed: 14.6 million people

Undiagnosed: 6.2 million people

Approximately 15% of Approximately 15% of patients with diabetes patients with diabetes will have a foot ulcer will have a foot ulcer and those who and those who develop an ulcer, 6% develop an ulcer, 6% will be hospitalized will be hospitalized due to infection or due to infection or other ulcer related other ulcer related complicationscomplications

Three Major Problems of an Open Three Major Problems of an Open WoundWound

HemorrhageHemorrhage

Mechanical Disruption Mechanical Disruption of Tissuesof Tissues

InfectionInfection

Lower Extremity WoundsLower Extremity Wounds

Diabetic Diabetic

VenousVenous

IschemicIschemic

CombinationCombination

Wound TypesWound Types

Acute Wounds: Wounds that heal with an Acute Wounds: Wounds that heal with an orderly and timely restoration of anatomic orderly and timely restoration of anatomic and functional integrityand functional integrity

Chronic Wounds: Wounds that appear to Chronic Wounds: Wounds that appear to be stagnated in the inflammatory or be stagnated in the inflammatory or proliferative phase. Accumulation of proliferative phase. Accumulation of excess extracellular matrix components or excess extracellular matrix components or matrix metalloproteinases (collageases-matrix metalloproteinases (collageases-elastase)elastase)

Wound Care Product HistoryWound Care Product History

Early accounts from 1650 BC described Early accounts from 1650 BC described standard treatments to include grease, honey, standard treatments to include grease, honey, and lint.and lint.The Egyptians and Greeks introduced various The Egyptians and Greeks introduced various metallic salt compounds, astringents, and metallic salt compounds, astringents, and antiseptics.antiseptics.Joseph Lister addressed wound sepsis leading Joseph Lister addressed wound sepsis leading to the use of specific chemical therapies to to the use of specific chemical therapies to manage wounds.manage wounds.Winter’s 1962 observations of the benefits of a Winter’s 1962 observations of the benefits of a moist wound environment regarding scar moist wound environment regarding scar formationformation

Central Dressing Selection ThemeCentral Dressing Selection Theme

Selection based on Selection based on experience not experience not scientific knowledgescientific knowledge

Studies focused on Studies focused on dressings as related dressings as related to wound type and to wound type and cost factorscost factors

Morrison 1987Morrison 1987

Gwyther 1988Gwyther 1988

Luker & Kenrick 1992Luker & Kenrick 1992

Flanagan 1992Flanagan 1992

Benbow 1994Benbow 1994

Bell 1994Bell 1994

Bux & Malhi 1996Bux & Malhi 1996

Vermeulen et 2006Vermeulen et 2006

Evidence Base MedicineEvidence Base Medicine

Evidence-based medicine is conscientious, Evidence-based medicine is conscientious, explicit, and judicious use of current best explicit, and judicious use of current best evidence in making decisions about the care of evidence in making decisions about the care of individual patients. (Waldman 2006)individual patients. (Waldman 2006)

Since wound care products are pharmaceuticals Since wound care products are pharmaceuticals -evidence is drug data, what the drugs are, how -evidence is drug data, what the drugs are, how they are used, and the latest recommendations they are used, and the latest recommendations for common and uncommon conditions.for common and uncommon conditions.

Evidence Base MedicineEvidence Base Medicine Five Step EBM Model (Akobeng 2005) Five Step EBM Model (Akobeng 2005)

A. Convert information needs into answerable A. Convert information needs into answerable questions. questions. B. Find the best evidence which will answer the B. Find the best evidence which will answer the questions. (Decide where to search)questions. (Decide where to search)C. Critical appraising of the evidence for its C. Critical appraising of the evidence for its validity and usefulness. (Relevant)validity and usefulness. (Relevant)D. Applying the results of the appraisal into D. Applying the results of the appraisal into clinical practice.clinical practice.E. Evaluating performance (Final outcome on E. Evaluating performance (Final outcome on

patient care) patient care)

Evidence Base Medicine Category Evidence Base Medicine Category of Evidenceof Evidence

Ia – Evidence from meta analysis of RCTsIa – Evidence from meta analysis of RCTsIb – Evidence from at least once RCTIb – Evidence from at least once RCTIIa – Evidence from at least one controlled study IIa – Evidence from at least one controlled study without randomizationwithout randomizationIIb – Evidence from at least one other type of IIb – Evidence from at least one other type of quasi experimental studyquasi experimental studyIII – Evidence from non-experimental descriptive III – Evidence from non-experimental descriptive studies studies IV- Evidence from committee reports or opinions IV- Evidence from committee reports or opinions or clinical experience of respected authoriesor clinical experience of respected authories

Evidence Base Medicine- Strength Evidence Base Medicine- Strength of Recommendationsof Recommendations

A – Directed based on category I evidence.A – Directed based on category I evidence.

B – Directed based on category II evidence or B – Directed based on category II evidence or extrapolated Directed based on category III or extrapolated Directed based on category III or extrapolated recommendation from category I or II extrapolated recommendation from category I or II evidence.evidence.

C – Directed based on category III or extrapolated C – Directed based on category III or extrapolated recommendation from category I or II evidence.recommendation from category I or II evidence.

D -Directed based on category IV or extrapolated D -Directed based on category IV or extrapolated recommendation from category I, II, III evidence.recommendation from category I, II, III evidence.

Evidence Based Medicine in Evidence Based Medicine in Wound CareWound Care

Much information available on evidence-Much information available on evidence-based medicine, including numerous based medicine, including numerous useful books, publications, journal articles, useful books, publications, journal articles, and websites.and websites.The search for evidence based medicine The search for evidence based medicine in wound care is still in the developmental in wound care is still in the developmental stages.stages.Much of the work in wound care has been Much of the work in wound care has been left to interpretation by wound care teams.left to interpretation by wound care teams.

Searching for Evidence-Based Medicine Related to Wound Searching for Evidence-Based Medicine Related to Wound Care Pharmaceuticals Care Pharmaceuticals Review Ryan et al 2003 OWM 49

(11) 67-75

SearchPub Med

www.pubmed.gov

Dates for literature1980-2007

Limitations:Clinical TrialsMeta-AnalysisRandomizedControl Trials

Mesh Terms“Product Class”

“Diabetic”“Foot”

“Ulcers”

400 Literature Citations

Wound Care ProductsWound Care Products

AlignatesAlignates

AntisepticsAntiseptics

Enzymatic ProductsEnzymatic Products

FoamsFoams

GauzeGauze

HydrocolloidsHydrocolloids

HydrogelsHydrogels

Antimicrobial or Antimicrobial or “biocides”“biocides”

Alternative MedicinalsAlternative Medicinals

ALGINATESALGINATES

These products are These products are produced from naturally produced from naturally occurring calcium and occurring calcium and sodium salts of alginic sodium salts of alginic acid found in a family of acid found in a family of brown seaweed.brown seaweed.Alginates are rich in Alginates are rich in either mannuronic acid or either mannuronic acid or guluronic acid, the guluronic acid, the relative amount of each relative amount of each influence the amount of influence the amount of exudate absorbed and exudate absorbed and the shape the dressing the shape the dressing will retain.will retain.

Alginate Dressings (RCTs)Alginate Dressings (RCTs)

Donaghue et al (1998) Evaluation of Donaghue et al (1998) Evaluation of collagen-alginate dressing in diabetic foot collagen-alginate dressing in diabetic foot ulcers.ulcers.

75 patients (2:1 ratio) for the collagen-75 patients (2:1 ratio) for the collagen-alginate vs gauzealginate vs gauze

80.6% reduction wound area vs 61.1%80.6% reduction wound area vs 61.1%

Complete healing was achieved in 24 Complete healing was achieved in 24 (48%) vs 9 (36%) after 8 weeks(48%) vs 9 (36%) after 8 weeks

Alginate Dressings (RCTs)Alginate Dressings (RCTs)

Bales et al (2001) Exploring the use of an Bales et al (2001) Exploring the use of an alginate dressing for diabetic foot ulcers.alginate dressing for diabetic foot ulcers.

Non-comparative, two center study not a Non-comparative, two center study not a RCTRCT

41 patients in two sites41 patients in two sites

6 weeks or until ulcer healed6 weeks or until ulcer healed

11 of 39 patients (28.2%) healed11 of 39 patients (28.2%) healed

AntisepticsAntiseptics

Antiseptics are disinfectants Antiseptics are disinfectants used on body surfaces to used on body surfaces to reduce the number of normal reduce the number of normal flora and pathogenic flora and pathogenic contaminantscontaminantsAntiseptics function as non-Antiseptics function as non-specific microbial inhibitors specific microbial inhibitors without a specific cellular without a specific cellular target.target. Smith A Critical Discussion Smith A Critical Discussion of the Use of Antiseptics in of the Use of Antiseptics in Acute Traumatic WoundsAcute Traumatic Wounds J Am Podiatr Med Assoc 2005 J Am Podiatr Med Assoc 2005 95: 148-153 95: 148-153

Antiseptic Concerns (Level “D”)Antiseptic Concerns (Level “D”)

Brennan & Leaper-microcirculatory

Cooter attractive agent

Lineaweaver-Fibroblast retards epithlialization

Kozol-Neutrophils “NO SAFE [ ]

Tap Water IrrigationTap Water Irrigation

A review of the reference material used to support this declaration of water’s negative effects could not be substainated.

Only one reference could be found declaring tap water contact with living cells at the wound’s edge caused cell break down with resulting tissue damage and pain discomfort.

Clinical Trials on Tap WaterClinical Trials on Tap WaterHall reviewed the medical literature regarding the effect of tap water verses normal saline on infection rates in acute traumatic wounds.

No association with the use of tap water and an increase rate of infection.

Angeras et al conducted a randomized study comparing the use of tap water with saline to cleanse acute traumatic soft tissue injuries.

Lower rate of infection in those wounds where tap water had been used to cleanse wounds; 5.4% with tap water compared to 10.3% with the saline group.

Bansal et al and Valente et al compared tap water and saline wound irrigation of simple lacerations in pediatric patients.

Bansal et al performed a blinded investigation while Valente et al conducted an unblinded non-randomized investigation.

Despite positive post irrigation cultures were found in Bansal et al’s investigation and clinical determination of infection in Valente et al’s study determined these findings were not significantly different between the normal saline solution and tap water groups.

Antiseptics in PracticeAntiseptics in Practice

The level of dilution that caused no damage to The level of dilution that caused no damage to fibroblasts at the same time maintaining bactericidal fibroblasts at the same time maintaining bactericidal activity was a 1/1000 concentration for povidone activity was a 1/1000 concentration for povidone iodine and 1/100 concentration for sodium iodine and 1/100 concentration for sodium hypochlorite.hypochlorite. While hydrogen peroxide and acetic While hydrogen peroxide and acetic acid solutions lose their bactericidal activity before acid solutions lose their bactericidal activity before they lose their tissue toxicity during dilution. they lose their tissue toxicity during dilution. Interestingly, the dilutions utilized in the cell culture Interestingly, the dilutions utilized in the cell culture experiments are below the strengths used in clinical experiments are below the strengths used in clinical practice.practice.

Enzymatic DebridersEnzymatic Debriders

Collagenase-Based Products

Papain-Based Products

Papain-Urea-Chlorophyllin Copper Complex


Collagenase, is an enzymatic debriding agent derived from Clostridium histolyticum belonging to the metallopeptidase family.

It specifically hydrolyzes peptide bonds and digests all triple helical collagen and will not degrade any other proteins lacking the triple helix. This is a unique feature of bacterial collagenase; since none of the other available proteases can digest collagen.


The enzyme liquefies necrotic tissue without damaging granulation tissue. Collagenase digests the lower portion of an escar working from the bottom up giving the appearance of working more slowly.Collagenase has been shown to be gentle to viable cells and might promote angiogenesis and epithelialization.


Papain is a nonspecific proteolytic enzyme derived from the fruit of the papaya tree (Carica papaya).Papain breaks down fibrinous material in necrotic tissue and requires the presence of sulfhydryl groups, such as cysteine, for its activity.It does not digest collagen, and it requires specific activators that are present in necrotic tissue in order to be stimulated.


Papain-urea preparations produce more Papain-urea preparations produce more exudate digesting eschar from the top which exudate digesting eschar from the top which may irritate the surrounding skin.may irritate the surrounding skin.

Papain-urea products should be applied daily Papain-urea products should be applied daily with a moisture retentive dressing.with a moisture retentive dressing.

Hydrogen peroxide solution may inactivate Hydrogen peroxide solution may inactivate papain as well as salts of heavy metals such as papain as well as salts of heavy metals such as lead, silver, and mercury have been shown to lead, silver, and mercury have been shown to inactivate papain. inactivate papain.

Papain-Urea-Chlorophyllin Copper Complex

Chlorophyllin, an anti-agglutinin, has been Chlorophyllin, an anti-agglutinin, has been added to preparations of papain/urea in an added to preparations of papain/urea in an attempt to reduce the pain.attempt to reduce the pain.Brett summarizes that there are favorable clinical results that reveal papain-urea chlorophyllin copper complex’s proteolytic action thoroughly cleanses lesions of all necrotic tissue debris and then maintains optimal circulation so that affected tissue will benefit from both hematological and nutritive elements.

Enzymatic Clinical TrialsEnzymatic Clinical Trials

Study Enzymatic Agent Level of Evidence

Lee & Ambrus (1975) Collagenase B

Parish & Collins (1979) Collagenase B

Rao et al (1975) Collagenase B

Vetra & Whittaker (1975) Collagenase B

Hansbrough et al (1995) Collagenase B

Muller et al (2001) Collagenase A

Pullen et al (2002) Collagenase A

Enzymatic Clinical TrialsEnzymatic Clinical TrialsKonig (2005) Collagenase A

Marazzi et al (2006) Collagenase B

Gasser (1940) Papain Emulsion B

Miller (1956) Papain-Urea B

Morrison & Casali (1957) Papain-Urea-Chlorophyllin B

Katz el at (1956) Papain-Urea-Chlorophyllin B

Carter (1958) Papain-Urea-Chlorophyllin B

Burke & Golden (1958) Papain-Urea-Chlorophyllin B

Alvarez et al (2002) Collagenase A Papain-Urea-Chlorophyllin

CMS Statement 2008CMS Statement 2008

FDA approved Santyl FDA approved Santyl will not be affectedwill not be affected

Products contain Products contain papain/urea and papain/urea and chlorophyll complex chlorophyll complex are scheduled to be are scheduled to be removed from 2008 removed from 2008 Medicare Formulary Medicare Formulary Reference FileReference File

FOAMSFOAMS

Foam dressings are Foam dressings are manufactured as manufactured as either polyurethane or either polyurethane or silicone form with silicone form with either hydrophilic or either hydrophilic or hydrophobic hydrophobic properties.properties.They transmit They transmit moisture vapor, Omoisture vapor, O22, , and thermal and thermal insulation.insulation.

Foams (RCTs)Foams (RCTs)

Lohmann M et al (2004) Safety and Lohmann M et al (2004) Safety and performance of a new-adhesive foam performance of a new-adhesive foam dressing for the treatment of diabetic foot dressing for the treatment of diabetic foot ulcers.ulcers.Open Non-comparative, prospective study Open Non-comparative, prospective study 35 out of 37 patients completed study35 out of 37 patients completed study6 weeks6 weeksRelative wound area reduction from 100% Relative wound area reduction from 100% to 40%to 40%

Gauze and SpongesGauze and Sponges

This cotton product This cotton product has relative wide has relative wide weave through which weave through which new tissue can grow.new tissue can grow.

Gauze dressings are Gauze dressings are manufactured in manufactured in many forms.many forms.

Gauze and SpongesGauze and Sponges

Gold standard (Wet to Dry Gauze Gold standard (Wet to Dry Gauze Dressing)Dressing)

Comparative studies with impregnated Comparative studies with impregnated productsproducts

Randomized Controlled StudiesRandomized Controlled Studies

Often used for economic studies for cost Often used for economic studies for cost analysis-Material cost for the dressing and analysis-Material cost for the dressing and labor expenseslabor expenses

HydrocolloidsHydrocolloids

Hydrocolloids are Hydrocolloids are hydrophilic colloid particles hydrophilic colloid particles (sodium (sodium carboxymethycellulose,carboxymethycellulose,

gelatin, pectin, elastomers, gelatin, pectin, elastomers, and adhesives) bound to and adhesives) bound to polyurethane foams that are polyurethane foams that are impermeable to bacteria impermeable to bacteria and facilitating wound and facilitating wound debribementdebribement

Hydrocolloids RCTsHydrocolloids RCTs

Apelqvist et al (1990) Topical treatment of Apelqvist et al (1990) Topical treatment of necrotic foot ulcers in diabetic patients: a necrotic foot ulcers in diabetic patients: a comparative trial of DuoDerm and MeZinccomparative trial of DuoDerm and MeZincAn Open Randomized Controlled TrialAn Open Randomized Controlled Trial44 patients44 patients14 of the 21 patients treated with MeZinc 14 of the 21 patients treated with MeZinc had their necrotic ulcers improve by at had their necrotic ulcers improve by at least 50% compared to 6 out of 21 of least 50% compared to 6 out of 21 of hydrocolloid dressinghydrocolloid dressing

Hydrocolloids RCTsHydrocolloids RCTs

Varma et al (2006) Efficacy of Polyurethane Varma et al (2006) Efficacy of Polyurethane Foam Dressing in Debrided Diabetic Lower Limb Foam Dressing in Debrided Diabetic Lower Limb Wounds.Wounds.

Patients randomly assigned to study or control Patients randomly assigned to study or control group (conventional gauze dressing)group (conventional gauze dressing)

48 patients (24 patients in each group)48 patients (24 patients in each group)

There was a significant reduction in the time There was a significant reduction in the time taken for wounds to heal 22.5 compared to 52 taken for wounds to heal 22.5 compared to 52 days.days.

HydrogelsHydrogels

Hydrogels are non-Hydrogels are non-adherent, water adherent, water based, or glycerin based, or glycerin based amorphous, based amorphous, crossed-linked crossed-linked polymer gels.polymer gels.Hydrogels can help Hydrogels can help reduce pain, reduce pain, decrease wound decrease wound temperature and temperature and inflammation.inflammation.

Hydrogels RCTsHydrogels RCTs

Smith (2002) Debridement of diabetic foot Smith (2002) Debridement of diabetic foot ulcers.ulcers.Three Hydrogel RCTs suggested that hydrogels Three Hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or are significantly more effective than gauze or standard of care in healing diabetic foot ulcers.standard of care in healing diabetic foot ulcers.Scanlon (2003) Review: debridement using Scanlon (2003) Review: debridement using hydrogel appears to be more effective than hydrogel appears to be more effective than standard wound care for healing diabetic foot standard wound care for healing diabetic foot ulcersulcersThere is little good quality clinical evidence to There is little good quality clinical evidence to indicate superiority of any one hydrogel over indicate superiority of any one hydrogel over anotheranother

Broad-Spectrum Antimicrobials Broad-Spectrum Antimicrobials (Biocides)(Biocides)

Cadexomer Cadexomer iodineiodine

SilverSilver

Cadexomer IodineCadexomer Iodine

Iodine is a potent broad spectrum Iodine is a potent broad spectrum antiseptic agent.antiseptic agent.Improved formulations of iodophors Improved formulations of iodophors “carriers” release low levels of iodine over “carriers” release low levels of iodine over a longer period of time.a longer period of time.Over the recent years the clinical use of Over the recent years the clinical use of silver and polyhexamethylene biguanide silver and polyhexamethylene biguanide products have been favorably embraced products have been favorably embraced when compared to cadexomer Iodinewhen compared to cadexomer Iodine

Cadexomer Iodine RCTsCadexomer Iodine RCTs

Apelqvist et al (1996) An economic analysis of Apelqvist et al (1996) An economic analysis of cadexomer iodine ointment and standard cadexomer iodine ointment and standard therapy.therapy. Compare Clinical effect and economic cost of Compare Clinical effect and economic cost of cadexomer iodine ointment and standard cadexomer iodine ointment and standard therapy.therapy.12 week open randomized comparative study12 week open randomized comparative study25 patients25 patientsTreatment with cadexomer iodine ointment Treatment with cadexomer iodine ointment show no clinical difference compared to show no clinical difference compared to standard therapystandard therapy

SilverSilver

Silver ions attack the cell membrane, the Silver ions attack the cell membrane, the membrane transport system, the RNA, the membrane transport system, the RNA, the DNA function, protein function, and inhibits DNA function, protein function, and inhibits bacterial mutation.bacterial mutation.

The longevity of silver ions in dressing The longevity of silver ions in dressing material due to controlled release material due to controlled release mechanisms insures that the wound mechanisms insures that the wound environment is hostile to bioburdenenvironment is hostile to bioburden

Silver Dressing (RCTs)Silver Dressing (RCTs)

Rayman et al (2005) clinical and safety of Rayman et al (2005) clinical and safety of sustained silver-releasing foam dressing.sustained silver-releasing foam dressing.

27 patients 6 weeks27 patients 6 weeks

Cross over study using Biatain dressingsCross over study using Biatain dressings

Silver foam is safe and easy to use and Silver foam is safe and easy to use and effectively supports healing and good effectively supports healing and good wound progress of diabetic ulcerswound progress of diabetic ulcers


Honey- Molan (2006) reviews the literature Honey- Molan (2006) reviews the literature to describe the evidence supporting honey to describe the evidence supporting honey as a wound dressing.as a wound dressing.Phenytoin – Scheinfeld (2003) Descriptive Phenytoin – Scheinfeld (2003) Descriptive reviewreviewEstrogen- (2005) A review of medical Estrogen- (2005) A review of medical literature literature Topical Insulin- (1999) 2 RCT double blind Topical Insulin- (1999) 2 RCT double blind placebo control trialplacebo control trial

Alternative TherapiesAlternative Therapies

Honey- Honey consists of simple sugars and is both Honey- Honey consists of simple sugars and is both sterile and inhibits growth of both Gram-negative and sterile and inhibits growth of both Gram-negative and Gram-positive organisms. Its antibiotic properties are Gram-positive organisms. Its antibiotic properties are attributed to its low pH, a thermolabile substance called attributed to its low pH, a thermolabile substance called inhibine, and its hygroscopic properties.inhibine, and its hygroscopic properties.

Molan summarized the clinical base evidence Molan summarized the clinical base evidence supporting the use of honey as a wound dressing. This supporting the use of honey as a wound dressing. This review reported the findings of 17 randomized controlled review reported the findings of 17 randomized controlled trials involving 1965 participants, as well as 5 clinical trials involving 1965 participants, as well as 5 clinical trials of other forms involving 97 participants treated with trials of other forms involving 97 participants treated with honey. honey.


The wound types treated with honey during these The wound types treated with honey during these control trials were either superficial burns, partial control trials were either superficial burns, partial thickness wounds, moderate burns, third degree thickness wounds, moderate burns, third degree burns, chronic leg ulcers, pressure ulcers, and burns, chronic leg ulcers, pressure ulcers, and surgical wounds.surgical wounds.

These studies compared honey to either silver These studies compared honey to either silver sulfadiazine, amniotic membrane, Vaseline gauze, sulfadiazine, amniotic membrane, Vaseline gauze, an occlusive dressing, mupirocin, povidone-iodine, an occlusive dressing, mupirocin, povidone-iodine, or a boiled potato peel.or a boiled potato peel.

Commercial products released in 2007 Commercial products released in 2007


This review presents a large body of evidence This review presents a large body of evidence supporting the use of honey as a wound supporting the use of honey as a wound dressing for a wide range of wounds because its dressing for a wide range of wounds because its antibacterial activity rapidly clears infection and antibacterial activity rapidly clears infection and protects the wound and it provides a moist protects the wound and it provides a moist healing environment without the risk of bacterial healing environment without the risk of bacterial growth occurring. Also, honey rapidly debrides growth occurring. Also, honey rapidly debrides wounds and removes malodor and its anti-wounds and removes malodor and its anti-inflammatory activity reduces edema and inflammatory activity reduces edema and exudate and prevents or minimizes hypertrophic exudate and prevents or minimizes hypertrophic scarring.scarring.


Phenytoin – Muthukumarasamy et al Phenytoin – Muthukumarasamy et al (1991) Topical phenytoin in diabetic foot (1991) Topical phenytoin in diabetic foot ulcersulcers100 patients (50 study) (50 control)100 patients (50 study) (50 control)Matched paired with sex, age, ulcer size, Matched paired with sex, age, ulcer size, and depthand depthMean time to heal 21 days for DPH and 45 Mean time to heal 21 days for DPH and 45 days with control dry sterile occlusive days with control dry sterile occlusive dressingdressing


Phenytoin – Pai et al (2001) Topical Phenytoin – Pai et al (2001) Topical phenytoin in diabetic ulcers: a double blind phenytoin in diabetic ulcers: a double blind control trialcontrol trial

57 patients completed trial57 patients completed trial

Marginal increase in reduction of mean Marginal increase in reduction of mean ulcer area after 3 to 4 weeksulcer area after 3 to 4 weeks

Treatment was better in Wagner grade II Treatment was better in Wagner grade II ulcersulcers

Developing a wound care product Developing a wound care product Formulary ReferencesFormulary References

Preece J. Development of a wound-Preece J. Development of a wound-management formulary for use in clinical management formulary for use in clinical practice. Professional Nurse 2004 20 (3) 27-29.practice. Professional Nurse 2004 20 (3) 27-29.

Posnett J. Making cost effectiveness the basis of Posnett J. Making cost effectiveness the basis of product selection. J of Wound Care 2006 15 (1) product selection. J of Wound Care 2006 15 (1) S14-S15.S14-S15.

Fikar CR and Delinosi BD. Wound-care Fikar CR and Delinosi BD. Wound-care resources on the internet: a second update. resources on the internet: a second update. JAPMA 2006 96 (3) 264-268.JAPMA 2006 96 (3) 264-268.

Developing a Wound Care Product Developing a Wound Care Product Formulary CriteriaFormulary Criteria

EfficacyEfficacyEffectiveness and SafetyEffectiveness and SafetyQuality of the Drug and Supply ChainQuality of the Drug and Supply ChainAvailability of Clinical expertise for Availability of Clinical expertise for questionsquestionsCost estimates to the institution, including Cost estimates to the institution, including costs of drug, hospitalization, and timecosts of drug, hospitalization, and timeAvailability of the DrugAvailability of the Drug

Developing a Wound Care Product Developing a Wound Care Product FormularyFormulary

Do not assume that all products within a Do not assume that all products within a particular category are the same.particular category are the same.Always challenge product suppliers to Always challenge product suppliers to provide evidence to support their claims.provide evidence to support their claims.The price of products used in the The price of products used in the treatment process is relatively a minor part treatment process is relatively a minor part of the overall cost.of the overall cost.Available resources thus must be used in Available resources thus must be used in the most efficient way possible.the most efficient way possible.

Developing a Wound Care Product Developing a Wound Care Product FormularyFormulary

LiteratureReview

BestEvidence

EvaluateOn

ClinicalBasis

Final ProductInclusion

Make aShort List

Of 2-3 productsClass

Challenge of Finding Evidence in Challenge of Finding Evidence in Wound ManagementWound Management

Majority of products are categorized as medical Majority of products are categorized as medical devices.devices.

They are deemed safe for use after successful They are deemed safe for use after successful investigations of safety based on Phase 1 and investigations of safety based on Phase 1 and Phase 2 trials yield satisfactory outcomesPhase 2 trials yield satisfactory outcomes

Thus the motivation for designing and Thus the motivation for designing and developing Phase 3 studies (RCTs) may be less developing Phase 3 studies (RCTs) may be less in the field of wound healing compared to other in the field of wound healing compared to other areas of clinical medicine.areas of clinical medicine.

Strategy for over coming the Strategy for over coming the Challenge Challenge

Development of the most appropriate design for Development of the most appropriate design for establishing evidence should be a priority for all establishing evidence should be a priority for all clinicians.clinicians.

An international working group of respected An international working group of respected leaders in the field should be formed to focus on leaders in the field should be formed to focus on this lack of evidence.this lack of evidence.

This group should be responsible for defining the This group should be responsible for defining the tools to be used to develop protocols for the tools to be used to develop protocols for the translation of RCTs into clinical practice.translation of RCTs into clinical practice.

ConclusionsConclusions

While there are many wound care products While there are many wound care products (Pharmaceuticals) available on the market, (Pharmaceuticals) available on the market, robust evidence of comparative effectiveness of robust evidence of comparative effectiveness of products is limited.products is limited.

Although there is some reliable evidence on the Although there is some reliable evidence on the management of venous leg ulcers, there is a management of venous leg ulcers, there is a lack of good quality data regarding the lack of good quality data regarding the effectiveness of products on other wound typeseffectiveness of products on other wound types

Documents

Wound Healing Pharmaceuticals: What the EBM Tells Us Robert G. Smith DPM., MSc., R.Ph., C.Ped PharmCon2008 Pharmcon is accredited by the Accreditation