3rd MeTA Philippines Forum Maramba Nelia Transparency in Selection of Essential Medicines for PNDF

8/10/2019 3rd MeTA Philippines Forum Maramba Nelia Transparency in Selection of Essential Medicines for PNDF

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. . . now is the time to stop butting heads and

start linking arms. It is not impossible to work

out a united plan that will be acceptable for all,

and in the end will benefit those who need it

most.Esperanza I. Cabral MD

S

ecretary of

H

ealth

Keynote Address at

The rd MeTA Philippines Forum


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TRANSPARENCY IN SELECTION of

ESSENTIAL MEDICINES FOR THEPHILIPPINE NATIONAL DRUG FORMULARY

(PNDF)

Nelia P. Cortes-Maramba, M.D.

Professor EmeritusDepartment of Pharmacology & Toxicology

College of Medicine, UP Manila

Member, National Formulary Committee


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Legal Basis

1. Republic Act No. 6675 GENERICS

ACT of 1988 (13 September)

An Act to Promote, Require and Ensure

the Production of an Adequate Supply,Distribution, Use and Acceptance of Drugs

and Medicines Identified by their Generic

Names.

Prescribed that it is the policy of the Stateto ensure the adequate supply of drugs

with generic names at the lowest possible

cost


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Sec. 4 The Use of Generic Terminology for

Essential Drugs and Promotional

Incentivesa) In the promotion of the generic names for

pharmaceutical products, special

consideration shall be given to drugs andmedicines which are included in the Essential

Drugs List to be prepared within one hundred

eighty days (180) from approval of this Act and

updated quarterly by the Department of Healthon the basis of health conditions obtaining in

the Philippines as well as on internationally

accepted criteria.


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Sec 3 Definition of Terms

(7) Essential Drugs List or National Drug

Formulary it shall consist of core list andcomplementary list

(8) Core list is a list of drugs that meets the

health care needs of the majority of thepopulation.

(9) Complementary List is a list of alternative

drugs used when there is no response to thecore essential drug or when there is

hypersensitivity reaction to the core essential

drug or when for one reason or another, the

core essential drug cannot be given.


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PROCESS of FORMULATING THE PNDF

consultative and participative processthrough

regular meetings among members of NFC

series of deliberation meetings with differentpanels of experts from

o Medical schools

o Philippine Medical Association

o Various specialty and subspecialty societieso Government and private hospitals

inputs from pharmaceutical companies

recommendations of other stockholders


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PNDF Volume 1 Essential Medicines

list 7thEdition (2008)

major step towards rational use of

medicines

medicines selection based on public

health relevance, evidence of efficacy and

safety, quality and comparative cost-

effectiveness


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NationalList of Essential Medicines

Subset of FDA registered medicines divided

according to different levels of care for higher

quality of care, better management of

medicines (improved quality control, morecost-effective use of health resources) and

ensures regular supply of essential

medicines resulting in

real health gain

Increased confidence on the health system


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Primary Care Medicines68 medicines

List of medicines intended for use in the Rural

Health Units To meet the immediate health needs of

majority of the population for commonly

encountered ailments all over the country.

Generally safe and do not require special

expertise and equipment for proper use.

Two categoriesFor use by All RHUs (N=30 medicines)

For RHUs with Physicians and other health

workers (N=68 medicines)


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Classificacions of Drug as Vital (V), Essential (E)

and less essential (L) based on the following

criteria: 1. frequency of occurrence of target

conditions2. severity of target conditions

3. therapeutic effects of the drug(curative, symptomatic relief, etc)

4. cost of therapy Classification is useful in prioritizing

procurement of medicines especially in resource-

poor areas

Dynamic list of medicines with periodic review

and updating in the light of new developments

and experiences and prevailing health needs of

our population


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GENERAL GUIDELINES FOR ESTABLISHING THE

PHILIPPINE NATIONAL DRUG FORMULARY

Drug selection must be based on the following

1. Relevance to diseaseindicated in the

treatment of prevalent diseases2. Efficacy and safetybased on adequate

pharmacologic studies especially among

Filipinos (Expanded Phase II clinical trials

and/or additional Phase III studies)3. Qualitymust meet adequate quality control

standard including stability and when

necessary bioavailability.


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General guidelines (Contd)

- compliance with WHO Certification Scheme on

the Quality of Pharmaceutical Products Movingin International Commerceproduct

manufactured in accordance with CGMP and

records whether or not the product has been

approved for marketing in the country of origin.

4. Cost of treatment regimen

5. Appropriateness to the capability of health

workers at different levels of health care.

6. Local health problems

7. Benefit/Risk ratio


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8. Preferential factors for evaluating therapeuticallyequivalent drugs

8.1 most thoroughly investigatedbeneficial propertiesand limitations

8.2 clinical utility for the treatment of more than onecondition or disease

8.3 most favorable pharmacokinetic properties for

improved compliance and minimize risk in

pathophysiological states

8.4 dosage form that is easy to dispense or easily orsafely administered to patient

8.5 greater acceptability by most patients

8.6 favorable stability under anticipated local conditions

for which storage facilities exist


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8.7 existence of local reliable manufacturing facilities

for its production

9. Single Formulations preferred. Fixed ratiocombinations are acceptable when

9.1 value of concomitant use of more than one drug is

clinically documented9.2 therapeutic benefit of the combination is greater

than the sum of the individual components

9.3 the combination is safer than individual drug

9.4 cost of combination product is less

9.5 compliance is improved

9.6 appropriate drug ratio in the combination is

satisfactory for the majority of the population


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10. Period of Review of Essential Medicines list

yearly

10.1 New drugs added if with distinct advantage over

drugs previously selected

10.2 Drugs with lower Benefit/Risk ratio should be

replaced by those with higher benefit/risk ratio

11. International NON-PROPRIETARY NAMES(INN) for drugs shall be used


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DRUG SELECTION FOR THE PHILIPPINE

NATIONAL DRUG FORMULARY

Acceptance safety, proven efficacy, quality and purity?

Disease/Condition/Indicationfound in the Philippines?

High prevalence of disease/condition in the Philippines?

Two or more therapeutically equivalent drugs?

Favorable benefit / risk ratio?

Thoroughly investigate / extensive clinical experience?

Favorable pharmacokientic properties?

Stable under anticipated local conditions?

(Accelerated and long term stability)

Cost-effective and/or reliable local

manufacturing facilities?

CoreList

Delist/Deny

Registration

Delist/DenyRegistration

Life saving

drug

Further

Review

Core

List

Comp.

List

Comp.List

Comp.

List

Comp.

List

Comp

list

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

No

No

No

No

No

No

No


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CRITERIA FOR INCLUSION ANDDELETION OF DRUGS FROM THE

PHILIPPINE NATIONAL DRUG FORMULARY

In addition to the guidelines as stated previouslythe National Formulary Committee consideredthe following criteria for including additional

drugs:1. The drug is needed for the prevention and treatmentof conditions not already covered in the existinglist;

2. The drug is more effective and/or less toxic than a

drug listed for the same indication;3. The drug is at least as effective and safe and of

lower cost than the drug listed for the sameindication; and

4. The drug is deemed essential for a specific DOH

health program/project.

C it i f I l i /D l ti (C td)


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Criteria for Inclusion/Deletion (Contd)

On the other hand, the following criteria wereapplied for deleting a drug from the list:

1. A more effective or equally effective but less toxic drugbecomes available;

2. In the light of further knowledge, the therapeutic efficacyof the drug is found to be unsatisfactory orquestionable;

3. Toxicity/Suspected toxicity or potential for abuse ordangerous interactions prove to outweigh its therapeuticvalue;

4. The drug has fallen into disuse and is no longeravailable;

5. The drug is no longer deemed cost-effective to othertherapies; and

6. The drug is fixed dose combination which does notsatisfy the requirements of A.O. 96 s, 1990.


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ANNEX A

PROCESS ALGORITHM FOR INCLUSION / DELETION OF PNDF DRUGS

Part 1 RVIEW OF CURRENT PNDF DRUGS

Check BFAD registry

Conduct systematic literaturereviewB

Consider for deletion if there are better drugs interms of efficacy, safety and cost

Consider for deliberation w/

resource persons

Has the drug been

withdrawn from the

market due to safety reason?A

Is there a new strong evidence of

Unfavorable risk: benefit?C

Is additional good evidence of

acceptable safety, proven efficacy,

quality and purity presentedduring deliberations?D

Delete

Mark for deletion

Retain the drug

Yes

Yes

Yes

No

No

No

ANNEX B


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REVIEW OF NEW DRUGS FOR POTENTIAL INCLUSION

Check BFAD registry

Is it officially registered

w/ BFAD & marketed in

the Philippines

Is the drug under

monitored release?

Conduct systematic literaturereviewB

Is there a goodevidence of favorable risk:

benefit? C

Is there any additionalstrong evidence that confirmsunfavorable risk: benefit from

interested parties? D2

Mark for possible inclusion

Is there a safer and more cost-effective, therapeutically

equivalent drug available?

Include the drug

Do not include

Is the drug needed for theprevention & treatment of conditions

not covered in theformulary?

Do not include

Do not include

Do not include

Do not includeYes

Yes

Yes

No

No

No

Yes

Yes

No

No

ANNEX B

ANNEX C


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ANNEX C

EVIDENCE TABLE

NoTITLE/AUTHOR

YEAR/JOURNALSTUDY

DESIGN

PARTICIPANT

DESCRIPTION

INTERVENTIONRESULTS/OUTCOME

GRADE OF

EVIDENCE

REMARKSEVENTS TREATMENT

DRUG GROUP

CONTROL

DRUG GROUP

(including

adverse

events)

No. of

events

Total #

of

patients

No. of

events

Total #

of

patients

Drug

*group means with standard deviationsmay be reported if the data are continuous

:


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Systematic Literature Review Process

Clinical Question: Is Drug x a safe and

efficacious drug for condition Y? Comprehensive Search: MEDLINE, HERDIN,

COCHRANE, EMBASEthrough the NATIONAL

DRUG INFORMATION CENTER based in UP

Manila

Critical Appraisal of abstracts/full text to verify

claims (RCT quality, level of evidence)

Examine similarities and differences of findings

across studies may perform META-ANALYSIS.

Independent search submitted by National Drug

Information Center (NDIC)


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LEVELS OF EVIDENCE (Evidence Based

Medicine or EBM)

Level A- STRONG

Several relevant high quality scientific studiesand results are convergent

Level BMODERATEAt least one high quality study and severaladequate studies

Level CLIMITED

At least one adequate study Level DWEAK OR NO Adequate Study

Expert Panel evaluationdoes not fulfill criteriaof scientific evidence


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Drugs listed by WHO requiring in vivo

bioequivalence studies based on the WHO Model

List of Essential Medicines which are immediate-

release, solid, oral dosage forms

Antimicrobials (9)

cefixime 400 mg

Clofazimine 100 mg

dapsone 100 mg

erythromycin stearate and ethyl succinate 250 mg

rifampicin300 mg and rifampicin FDC with otheranti-TB

medicinesulfamethoxazole 400 mg + trimethoprim 80 mg

sulfazalazine 500 mg

Trimethoprim 200 mg


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Antiparasitics (9)

albendazole 400 mg

artemether 20 mg + lumefantrine 120 mg

diloxanide furoate 500 mg

griseofulvin 250 mg

ivermectin 6 mg

mefloquine hydrochloride 250 mg

praziquantel 600 mg

pyrimethamine 25 mg

Sulfadoxine 500 mg + pyrimethamine 25 mg


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Contd Bioequivalence Studies

Anticancer/Immuneresponse modifyers (5)

azathioprine 500mgcyclosporine 25 mg

etoposide 100 mg

mercaptopurine 50 mg

tamoxifen citrate 200 mg

HIV/AIDS Medicines (5)

Endenavir sulfate 400 mg

Nelfinavir mesilate 250 mg

Neviraprine 200 mg

Itonavir 100 mg

Saquinavir 200 mg

OTHERS


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OTHERS

Acetazolamide 250 mg

Carbamazepine 200 mg

Furosemide 40 mg

Glibenclamide 5 mg

Haloperidol 2 mg

Iopanoic acid 500 mgMifepristone 200 mg

Nifedipine 10 mg

Retinolpalmitate 10 mg (200,000 IU)

Spironolactone 25 mg

Verapamil 80 mg

Added by NFC Phenytoin sodium

Theophylline anhydrous


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Primary Medical Care Drugs

A.For all Rural Health Units (RHUs)

B.For RHU & Staffed by Physicians and otherHealth Workers

C.Characteristics of Drugs Included

1. Occurrence of Target

conditions

Vital Essential Less Essential

Persons affected (% of

population)

> 5% 1-5% < 1%

Persons diagnosed(cases/100,000 population/year)

200 50-100 < 50

Persons treated (frequency of

target condition seen by health

workers)

Moderate Low Very low


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2. Severity of Target Conditions Vital Essential Less

Essential

LIFE THREATENING

(likely to cause death if untreated)

Possibly Infrequently Rarely

CHRONIC

(likely to cause recurrence,

relapse, continued disease)


DISABLING

(likely to cause permanent

disability if untreated)


RESTRICTING

(likely to cause loss of workingand housekeeping time)

Frequently Occasionally Infrequently


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Therapeutic

Effects

Prevention ofDisease,Cure of

DiseasePrevention ofComplication

Cure ofDisease,Prevention or

Treatment ofComplication

Relief and/ormitigation ofself-limited

diseasePALLIATIVEtreatment ofminorsymptoms/

complication4. COST

Average costof a singlecourse of

therapy (acutetherapy)

Averageyearly cost, oftherapy

(chronictherapy

Low

Low

Moderate

Moderate

High

High

3. DRUG ACTION Vital Essential Less Essential


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PHILIPPINE NATIONAL DRUG

FORMULARY Vol 1, 7thEDITION 2008

No. of Sections of Therapeutic Categories = 22

No. of Active Ingredients = 627

Core list = 350

Complementary List = 277No. of pharmaceutical products added = 45

No. of pharmaceutical products deleted = 32

No. of pharmaceutical products not available

in the market but considered essential (*) = 64No. of new drugs under Monitored Release = 38

No. of Dangerous Drugs (A1) = 19

(Internationally controlled)


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PHILIPPINE NATIONAL DRUG FORMULARY Vol 1, 7th

EDITION 2008 (Cont)

No. of Controlled Precursors and EssentialChemicals (A2) = 3

No. of medicines requiring specific expertise,

diagnostic precision, or special equipment

for proper use (1) = 155

No. of medicines with limited indications or

narrow spectrum of activity (2) = 136

No. of antibiotics in the PNDF to be used only

in hospitals with DOH accredited Antimicrobial

Resistance Surveillance Program (ARSP) (3) = 6

No. of list B medicines = 40

No. of medicinal plant products registered with

BFAD (*) = 5


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Thank you!


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. . . now is the time to stop butting heads and

start linking arms. It is not impossible to work

out a united plan that will be acceptable for all,

and in the end will benefit those who need it

most.Esperanza I. Cabral MD

S

ecretary of

H

ealth

Keynote Address at

The rd MeTA Philippines Forum

3rd MeTA Philippines Forum Maramba Nelia Transparency in Selection of Essential Medicines for PNDF

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