[e-drug] Moving towards a new definition of essential medicines?

e-drug
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E-DRUG: Moving towards a new definition of essential medicines?
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Dear All,

WHO has recently released the 19th Model list of Essential Medicines and
5th Model List of Essential Medicines for Children. The Model List is
considered a guiding beacon for all countries but the current list has
characteristic differences from the previous lists.

Many investigational agents, drugs for off-label indications, drugs not
registered by stringent drug regulatory authorities have been included in
the list. These are against the principles of selection of essential
medicines.

There are some more serious concerns addressed in the recently published
editorial - "Are we moving towards a new definition of essential
medicines?". Please follow the link to read the editorial

http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2015;volume=6;issue=3;spage=123;epage=125;aulast=Manikandan

I thought of sharing this editorial in this forum and invite your comments.

Best Wishes,

Dr. S. Manikandan MD, DNB, MNAMS,
Department of Pharmacology,
Jawaharlal Institute of Postgraduate Medical Education and research
(JIPMER),
Pondicherry, INDIA
drsmanikandan001@gmail.com

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Dear colleague,

     I fully agree with your suggestion - it is certainly a matter of
principle which should be discussed in Geneva. When I was a temporary
member of the advisory council of the Essential Medicines project I felt
quite uneasy when powerful pressure groups forced the program to add
scores of expensive anti-HIV drugs to the list, in a way indirectly
forcing countries where HIV-AIDS was a minor problem to purchase drugs
for which there was not a immediate need. The same is now happening with
the list of 12 new anticancer drugs which now have been added. Many
countries have no funds to buy them, and, in addition they lack the
facilities for their safe and effective use. The list was originally
meant to facilitate the acquisition of a restricted number of
life-saving drugs in circumstances and in countries with limited
facilities. WHO Europe did the same in Russia after the downfall of
communism, and it was a huge success. Outside pressure on the scientific
decisions may in the long run wreck the whole programme.

Your remarks are timely and to the point, though they may fall on deaf
ears in some circles. Good luck!

Dr.Leo Offerhaus,
Former acting head medicines division, WHO Europe 1991-1993.
offerhausl@euronet.nl

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E-DRUG: Moving towards a new definition of essential medicines? (3)
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Dear all,

   I share concerns with Dr Manikandan on the developments around the WHO
   Essential Medicines List. The examples in his editorial are clear, but
   I want to draw your attention to another aspect.

   When I worked in WHO, we developed the WHO Guidelines for the
   Pharmacological Treatment of Persisting Pain in Children (2012). These
   evidence-based guidelines concluded that the evidence for all strong
   opioid analgesics is relatively low (as for so many more medicines that
   old); that the strongest evidence is for morphine; and that there is
   no evidence to prefer one opioid full-agonist analgesic over another
   when it comes to the need for alternatives. However, two alternatives
   should be available at all times, because many patients do not well on
   one opioid and in such a case pain can often be managed with another
   opioid.

   Based on these paediatric guidelines, I submitted an application in
   2012 to add child-friendly morphine preparations to the list for
   children. Furthermore, I submitted an application that at least two
   alternative opioids should be available in addition to morphine.
   Because there is no evidence for preferring one opioid over another, I
   suggested that the square box should be used indicating that is an
   example of a class and that a footnote explains that at least two
   alternatives, e.g. hydromorphone and oxycodone, should be available. As
   this aspect is not age-related, the application extended to the EML for
   adults as well.

   When the 18th Model List and the 4th Model List for Children were
   published in 2013, I was amazed to find that their wording limit the
   alternatives to two opioids only by saying "alternatives limited to
   hydromorphone and oxycodone", in spite that there is not any scientific
   reason for such a limitation or to prefer these two alternatives over
   several other alternative opioids, like methadone or fentanyl.

   This limitation is a novelty in the EML and it works out as a
   suggestion to governments not to allow other opioid analgesics accepted
   for pain management world-wide. The chosen wording is prohibitive for
   having an optimal number of alternatives available for difficult cases
   and therefore it is very unfortunate. It is also a violation of the WHO
   policy guidelines for access to controlled medicines that rules should
   not be applied any stricter on controlled medicines than on
   non-controlled medicines unless good justification available.

   Not having been able to find any explanation on what happened in the
   expert meeting preceding the publication of the lists in 2013, I
   assumed that this all was a misunderstanding. Therefore, for the 2015
   meeting, I submitted an application to correct this, but it was
   rejected again. The Secretary explained this to me with "As you recall,
   the EML generally does not list ALL possible options in a class,
   especially when there are large differences in price amongst the
   alternatives - which is the case for the opioids. The Committee found
   that there was no reason to move from this position." However, to
   everybody who looks at other medicines with a square box indicating
   that they are listed as an example of a class, it will be clear that
   this is a specious argument.

   I feel that the Committee put its bias against controlled medicines in
   the EML without any reasonable justification. While the entire world,
   including the World Health Assembly in its palliative care Resolution
   67.19 of May 2014, is moving away from drug control policies that leave
   over 80% of the world untreated for moderate and severe pain, the
   Expert Committee on the Selection and Use of Essential Medicines seems
   now having been recruited as an squadron in the War on Drugs at the
   eleventh hour.

   Best regards,

   Willem Scholten Consultancy
   Willem Scholten PharmD MPA
   Consultant - Medicines and Controlled Substances
   Wielsekade 64
   3411 AD Lopik, the Netherlands
   T: +31 348 769 029
   M: +31 6 4847 3368
   E: [1]wk.scholten@xs4all.nl
   Skype: wimscholten
   Twitter: @WKScholten
   Chamber of Commerce number: 59656832
   VAT Identification number: NL067732380B01

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E-DRUG: Moving towards a new definition of essential medicines? (4)
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[Response to Offerhaus' posting. Moderator]

Actually some countries lack funding for antibiotics. Does that mean
antibiotics should be off the essential medicines list?

Best wishes

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Dear Mr. Scholten,

The problem you mentioned is quite a different one because you are
asking for a safe medium-strength analgesic because there is a void
between paracetamol/NSAIDs on the one hand, and opiods on the other.
(Semi-) synthetic opioids do not form the solution, because at equal
analgesic effect secondary effects and adverse reactions are the same as
those of morphine. Recently some people, particularly from Eastern
Europe, have advocated the use of the old drug metamizol, but that again
is "between the devil and the deep blue sea". So far industry has not
managed to produce a suitable alternative, the last failure being the
COX inhibitors. That is not a problem that WHO can solve, though they
should put additional pressure on the pharma industry to accelerate
development of suitable safe pain killers. Let's focus on
Dr.Manikandan's remarks instead.

Best regards,

Leo Offerhaus.
offerhausl@euronet.nl

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Dear Dr Offerhaus
   This is not my point. I am discussing full-agonist opioid analgesics,
   not non-opioid analgesics. The guidelines advisory group for the WHO
   pediatric treatment guidelines recommended that morphine should be
   available, plus at least two such strong opioid analgesics as an
   alternative for patients who do not react well to morphine.
   
On the EML, it was then introduced that the alternatives should be
   limited to hydrocodon and oxycodone, in this way excluding methadone
   and fentanyl with the argument that some substances are expensive. This
   is pure nonsense, as methadone is the cheapest opioid analgesic of all,
   and in some countries (e.g. Greece), fentanyl is cheaper than morphine.
   In most countries (together having 80% of the world population) access
   to opioids is very low and often absent. In many of these countries
   only one or two full-agonist opioid analgesics are on the market - out
   of the five full-agonist opioids that are commonly in use in
   industrialized countries nowadays. The EML excludes now two of them,
   increasing the global crisis in pain management, in particular in
   countries where fentanyl or methadone is among the alternatives for
   morphine. The mechanism is novel and it is my view that it is not by
   hazard that this is applied for the first time on controlled
   substances: the Expert Committee for the Selection of Essential
   Medicines shows an unjustified fear for the use of opioid analgesics
   that does not find any justification in the scientific literature, and
   it comes up with false justifications for its measure.
   
In this way the Expert Committee counteracts many WHO policies like the
   WHO pediatric pain guidelines, the WHO policy guidelines on access to
   controlled medicines and the WHA resolution on palliative care.
  
I hope I made myself more clear now,

   Best regards,
   Willem Scholten

   Willem Scholten Consultancy
   Willem Scholten PharmD MPA
   Consultant - Medicines and Controlled Substances
   Wielsekade 64
   3411 AD Lopik, the Netherlands
   T: +31 348 769 029
   M: +31 6 4847 3368
   E: [1]wk.scholten@xs4all.nl
   Skype: wimscholten
   Twitter: @WKScholten
   Chamber of Commerce number: 59656832
   VAT Identification number: NL067732380B01

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E-DRUG: Moving towards a new definition of essential medicines? (10)
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Dear colleagues,

The term 'essential drugs' appears to be subjective? It reminds me of the use of the term 'Basic Package of Care'. In some circles, the term 'Basic Package of Care' refers to the provision of basic, primary- type of health services. Tertiary care, the sort of high end, high cost health care services such as cancer screening and treatment, would be considered not part of the 'Basic Package of Care'. If that line of thought is stretched, it would imply that the basic package of care will not attend to the more complex diseases (cancer? dialysis? NCDs?) that require high cost diagnosis, care and treatment. What then, to do about these, new emerging diseases, for example, that now have become common?

Not so long ago, I came across this opinion / position from some healthcare planners and health professionals: 'if we cannot afford the treatment, then the disease does not exist'.

The idea of an Essential Drugs List certainly helps to concentrate the mind of governments, so that there is control on what products to use, procure and use in the health care system for the diseases prevailing. I do not believe the EDL strategy aims to prevent or restrict the inclusion of any other products, event when those products are expensive. In that regard, ARVs, anti- cancer drugs, for example, would immediately fit the term, Essential Drug, in spite of their cost.

So, if WHO recommends new and expensive drugs, I guess it is from a recognition that the primary purpose of organizing the list of essential requirements, is indeed about affordability, reducing wastage, reducing cost, creating control, prioritizing, etc, particularly in resource- limited settings. But it is also about ensuring that we are able to treat all diseases that we are faced with (not suggesting that we'd ignore any disease). Furthermore, the disease profiling and the health programming activities in many countries are mature enough to recognize the need to attend to the more sophisticated diseases that require the more expensive products, that are now, also essential. So, I think that the above consideration is what the new List of recommendations from WHO is suggesting.

Regards,
Bonnie

Bonface Fundafunda PhD., MBA., B.Pharm
Managing Director,
Medical Stores Limited
P.O. Box 30207
Mukwa Road, Plot 6446
Lusaka,
Zambia
Tel (Dir): +260 211 246510 (Dir)Tel (General): + 242768/ 244105 / 242346
Fax: +260 211 246288
Mobile: + 260 979 25 29 00
Email: bonface.fundafunda@medstore.co.zm
Web: www.medstore.co.zm

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E-DRUG: Moving towards a new definition of essential medicines? (11)
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In addition to what Boneface is saying: high priced medicines need
governments' actions to cut their prices.

When WHO launched 3x5, donors and others thought the organisation had gone
mad. And yes, at $10,000/person/year -as the price of ARVs used to be-it
would have been mad to imagine treating 3 million. But at $360
/person/year it has been possible to mobilise global efforts to treat 10
million people now.

Best wishes Mohga

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E-DRUG: Moving towards a new definition of essential medicines? (12)
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Dear Colleagues,

I hope our current debate will deliver the relevant clarity and way forward on this important subject.

In the early 90s, I had the opportunity to represent the Commonwealth Pharmaceutical Association on a couple of biennial meetings of the Expert Committee and, I recall that whatever the product inclusion/exclusion proposal before the committee, was very robustly and professionally debated by the very best folks in the field, and resolved with the best available options at any one time. At that time, the engagement of the general professional public prior to the meeting was not so extensive, but I noticed that by late 90s into the 2000s, the public was extensively invited to contribute towards the work of the committee, regarding proposals that would be tabled for the forthcoming committee deliberations.

If this process is currently the case, then the question on my mind is 'why are the important issues raised by Dr. S. Manikandan and follow-up postings only coming up now?, or were they raised but ignored?

Allowing for the possibility that procedures and principles of reviewing and updating the EML may have changed, I have quickly checked the WHO website and I encourage colleagues who have not done so to review the short preamble write-up to the upload of the current list headed:

Criteria for Selection of Essential Medicines, Essential Medicines Lists, and Global Concept

The text which attracts my attention, and which could probably explain some of the apparent discrepancies now being discussed, is the one headed 'A global concept' and I reproduce this below for ease of reference:

The concept of essential medicines is forward-looking. It incorporates the
need to regularly update medicines selections to reflect new therapeutic
options and changing therapeutic needs; the need to ensure drug quality; and the need for continued development of better medicines, medicines for
emerging diseases, and medicines to meet changing resistance patterns.
I must confess I find some of these objectives/principles, e.g. 'forward
looking', 'development of better medicines', rather unclear in as far as
my previous experience goes, and further clarification would be helpful.

Having worked for over two decades across multiple UN Agencies involved in improving access to medicines in countries, especially those with fragile and/or highly compromised health infrastructures, my concern is not so much what gets listed in the EML( WHO or National), but rather what actions countries specifically take to ensure their citizenry benefit from the intended purpose of the list.

I will like to use the issue of Folic Acid which has been raised as a typical example with which I have extensive experience. It may be recalled that the WHO Expert Committee on Essential Drugs agreed during its 11th meeting in Geneva, Switzerland in November 1999, to recommend to countries to change from the old formulation of 60 mg elemental iron with 0.20mg Folic Acid to 60 mg elemental iron with 0.4 mg Folic acid. I see that to this day there appears to be ongoing debate on the position of Folic Acid; and I suspect there are countries which may still not have taken any informed view on this matter. The result is that benefit optimization is delayed. Usually, it is only when a public procurement tender is floated for this item that all the available options on the national market begin to show up in bids and complicate evaluations!

My point, in summary, is that I think countries must honestly and professionally use The WHO EML to take care of their specific needs, expressed in National EMLs and, even more, use the list in their routine health supply chain work. I appreciate the numerous 'other factors' at play, but this is the only way we can avoid being distracted into the global whirlwind of possible product options, present as well as future!