O

nce every two years, the World Health Organization releases a list of medications it thinks should be available, if needed, to all the people of the Earth. The latest iteration of the essential medicines list is slated to be released this week.

It’s a formulary, a compendium like the ones health insurers such as Kaiser Permanente or Harvard Pilgrim maintain to help them determine which medicines should be covered by their policies.

That may sound dull or at least rather wonky. But there are real-world implications when a drug makes — or is not approved for — this list.

advertisement

The move to include HIV drugs in 2002 arguably helped to make lifesaving antiretrovirals available to AIDS patients in developing countries. More recently, the addition of game-changing hepatitis C drugs to the list appears to have put them on a similar trajectory.

Sign up to our Daily Recap newsletter

Please enter a valid email address.

The list is meant to help countries figure out how to prioritize spending on medications. It’s a model that many use to craft their own drug formularies — while individual countries may make tweaks here and there, they don’t each need to set about inventing this wheel.

While the process isn’t easy, the thinking behind it is.

“Some drugs are more important than others. … And this is independent of cost,” explained Nicola Magrini, a WHO scientist and secretary to the expert committee on the selection and use of essential medicines, which draws up the list.

Here are some facts about the essential medicines list — its history and some things to look for when the 2017 iteration is published.

Its birth was mired in controversy.

When the WHO set out to draft the first essential medicines list in the late 1970s, the United States and other pharmaceutical exporting countries weren’t pleased. Picking drugs for the list implied something about the drugs that didn’t make the cut.

“It was the concept that some medicines were more essential than others, which meant that some medicines were less essential than others,” said Dr. Richard Laing of Boston University’s Center for Global Health and Development. Laing formerly worked at the WHO and was involved in earlier iterations of the list. “No manufacturer wanted to have the suggestion that their medicine was less essential, less necessary than others.”

The list-making process has evolved.

For the first couple of decades, the list was drawn up based on expert advice. But that and other things changed shortly after the turn of the century.

Since that time, the selection process has used an evidence-based approach. The committee drawn together to update the list reviews the studies that have been conducted that either support a recommendation to include a drug or to delete it from the list.

There have been other changes, too. Before 2001, a drug had to be needed by a majority of the population to be included on the list, which meant medicines for uncommon diseases didn’t make the cut. But that criterion was dropped, said Magrini, and the list now includes medications like factor VIII, a clotting protein for hemophiliacs, and surfactant, which opens up the lungs of premature babies.

A drug’s cost was a deciding factor prior to 2001, Magrini said, with the idea being that a medication’s price should be low and affordable. But that’s a difficult bar to set when you’re looking at the whole world, he noted. “Even a dollar a month can be too much in sub-Saharan Africa.”

Now decisions are based on a drug’s usefulness, its safety and effectiveness, and the quality of the evidence supporting it.

The process is a two-way street.

Anyone — an individual, an organization, a pharmaceutical company — can submit a drug for inclusion. The WHO gets about 100 such applications every time it updates the essential medicines list, Magrini said.

Likewise, anyone can apply to have a drug stricken from the list. A malaria drug, amodiaquine, was added, dropped, then reinstated on the list in the 1990s.

One of the things people will be watching in this year’s list is whether oseltamivir — the flu medication sold as Tamiflu — will be cut. A group of academics who have long suggested the drug is more hype than help have asked that it be dropped.

Flu experts at the WHO have countered, saying the medication is the best of a very scant number of options for treatment of severe influenza.

Making the list can put expensive drugs within reach of more people.

In 2002, antiretroviral drugs, which can add decades to the lives of people infected with HIV, were listed for the first time. They were costly — well beyond the reach of the African countries hardest hit by the AIDS epidemic.

But their addition to the list occurred around the time of the creation of the Global Fund to Fight AIDS, Tuberculosis, and Malaria. The next year, PEPFAR — the President’s Emergency Plan for AIDS Relief — was born.

The confluence of those events spurred generic production of the listed HIV drugs, and that competition sent prices tumbling. The result: Millions more people had access to these critical drugs. Laing said this is one of the best examples of what adding a product to the list can do.

Some commonly used drugs have never made it to the list.

A number of drugs are widely prescribed to people with mild to moderate Alzheimer’s and other forms of dementia. The evidence for their efficacy is slender, yet they are still used.

None of those drugs is on the essential medicines list. “They have never been rejected, however,” Magrini said. “No one has ever proposed them — since they knew, probably, we would have rejected [them].”

The list can still kick up a controversy.

Medications are assessed based on how well they work and how much they are needed. Whether they will conform to a country’s religious or ethical beliefs is not part of the discussion.

So emergency contraception — the so-called morning after pill — is on the essential medicines list. This year the committee reviewed a proposal to include the “week-after pill,” Magrini said. He offered no clues on how the committee ruled on any of the applications before it.

A couple of things to watch for.

The essential medicines list is long. The full report, Magrini said, is about 500 pages. There were about 400 medicines listed in the 2015 iteration.

But here are a couple of issues Laing is watching for: Will long-acting analogue insulin be added to the list? And will the so-called polypill, the combination of four heart medicines, finally make the cut?

Laing opposes the insulin proposal, arguing — as do others — that the product is much more costly than human insulin but there’s minimal evidence to suggest it is any more effective.

He noted the case of Kyrgyzstan, which spends about half of its diabetes budget on analogue insulin — but by doing so only gets enough to meet about one-tenth of the country’s needs.

“If you’re in that situation, clearly you’re better off purchasing all your insulin as human insulin, because it’s pretty much the same as the analogues, and yet human insulin goes a lot further. You can buy a lot more,” he said.

As for the polypill, it’s a combination of a statin to lower cholesterol, a beta blocker, blood pressure medication, and aspirin. Proponents argue it is a cheap and effective way to improve the treatment of people who have had a heart attack or a stroke (each requires a different formulation), but some experts prefer individualizing treatment to the patient.

The polypill has been submitted and rejected twice before. Is 2017 its year? More to come.

Leave a Comment

Please enter your name.
Please enter a comment.

  • Treatment of Medical ailments is a right of every human. Pain is a Medical ailment.

    But 91 people die a day from an opioid overdose.

    The opioid crises is a difficult problem to solve.  I don’t believe people understand that there are many reason for pain and that there is no one magic pill.  The Institute for Clinical and Economic Review (ICER) recently reported that Abuse Deterrent Formulations (ADF) and Extended Release (ER) opioids are not effective clinically and do not provide an economic justification for their use.  I can see it.  These products contain a higher dose of opioids that is supposed to be “slow released” which is contrary to the desire of addicts who want a “quick fix”. Giving more opioids to an opioid addict certainly does not make sense. Also, according to the FDA, ADF and ER products are only responsible for 10% of the opioid overdoses, are very expensive, and are difficult for patients to obtain.   Finally ADF and ER products are subject to easy abuse by  simple oral overconsumption. 86% of the opioids are abuse via the oral route.  Take too many of these products and you still die.  What we should be doing for the opioid overdose epidemic is to attack the immediate release (IR) opioids which represents 90% of the opioid overdoses. ADF & ER products are still an important part of the solution in dealing with chronic pain but may not solve the opioid overdose epidemic.

    The government has set policy limiting IR opioids. We know limiting opioids makes logical sense but in the real would it doesn’t.  In 2013, 137 million Hydrocodone prescriptions were written and 48 people died a day from opioid overdoses.  In 2015, the government changed Hydrocodone from Schedule III to Schedule II and limited Hydrocodone to 99 million prescriptions and yet 91 people died a day from opioid overdoses – almost double the amount of people died per day after access to opioids were limited. The Government wants to limit Hydrocodone to 59 million in 2017 and one has to ask how many more people will die a day from opioid overdoses?

    Take the alcohol issue. Ban alcohol -18th amendment -and people distilled their own and went blind. Repeal of the ban followed – 21st amendment. It is better to control alcohol, tax it and provide healthcare to more people. Voila the solution to Opioid epidemic.

    Doctors write prescriptions.  Pharmacists fill the prescription.  What prevents the patient from taking 1 pill or 10 pills or the bottle of pills?  Absolutely nothing!  The problem of the opioid overdose epidemic is difficult to solve. There are many reason for pain and many treatments for pain. There is no one magic pill. 90% who overdose on opioids are returned back onto opioids within 2 weeks.  Government policy has misdirected opioid policy to limiting opioids.  Patients with limited access first turn to sharing pills with friends and family, then to Heroin.  The Heroin addiction and death rate has quadrupled in the last decade. 

    The government believes Naloxone (Narcan) and Buprenophine (Suboxone) will solve the opioid crises.  Narcan is used in people already overdose and Suboxone is used in people already addicted.  It seems that these two drugs are a little too late in the treatment scheme.

    The high death rate will continue  because no one has addressed this vital need.  New ER and ADF opioids are expensive and science has not proven their efficacy.  ER and ADF opioids are thought to be abuse deterrent but they are just as addictive as IR opioids.  The main reason for concern is that ER and ADF contain high dose opioids and do not address overconsumption which is the most common form of prescription opioid abuse.  Take more ER and ADF opioids than prescribed and patients will still die.  Giving an opioid addict more opioids for their addiction is illogical.

    85% of the opioid overdose death involves simple over consumption of opioids which is a major part of the problem.   Reverse engineering of this problem by examining the outcome first can lead to a solution.  Taking advantage of over consumption as a solution seems counterintuitive until it is explained. Opioids cause death by depressing respiration until respiratory arrest occurs.  Over consumption of opioids leads to greater respiratory depression in a dose dependent fashion.  Simultaneous introduction of a potent respiratory stimulant combined with the opioid would predictably lead to greater respiratory stimulation also in a dose dependent fashion. In support of this patent, it has been shown that animals given respiratory stimulants will  functionally antagonize the opioid induced respiratory depression that occurs with opioid overconsumption.   A combination oral drug consisting of a respiratory stimulant and  an opioid, benzodiazepine or barbiturates with the goal to treat pain and prevent accidental death in 100 million chronic pain patients who compliantly take opioids, in 20 million patients who intentionally abuse opioids and in the 33,000 patients a year who fatally overdose on opioids.  For opioid abusers and opioid overdose patients who accidentally and intentionally over consume pills, one pill could then be used to treat pain and prevent death in all opioid consuming patients.

    Consider a smart safer opioid combo pill to address the opioid overdose epidemic.  Patient compliance is ensured to prevent oral overconsumption and death. Should oral overconsumption occur a safer opioid would prevent respiratory depression and death. 

    A solution

    • John, your facts are wildly inaccurate. You need to look closer at the CDC death data. You will find that a large number of opioid deaths are actually caused by acetaminophen or alcohol. In 15 years 183,000 have died, 15,000 a year. Furthermore, this number is inaccurate due tot the co-administration of other drugs including alcohol, heroin and cocaine. If this is really about preventing deaths and overdoses, the best thing to do is give access to narcan to patients. Second, allow addicts that are NOT staying clean to have a safe place to use without fear of arrest that has people to administer narcan. This is working in Canada. I have seen two (2) cancer patients denied pain medications for over 48 hrs in the last week, that is absurd. If people get a steady supply from a doctor and can safely take it, the likelihood of death diminishes. However when they buy pills or heroin from street sellers, the dosage is wildly fluxuating and overdoses increase.

      Please, please take some real time to look at the CDC data and understand that drs are not in anyway causing this. Laws and enforcement is causing this. Addiction is a medical issue and should be treated as such. You can make all the safer medications you want, but if they do not work, no one will use them. I have taken oxycodone and hyrdocodone for over 16 years, i am currently 34. Without them, i would be dead. I cannot move due to pain. I take my meds as prescribed and tell my dr when they dont work. After all these years i am currently only at 20mg OC every 12hrs and 10mg HC every 4 hours as needed. I also take mobic, get cortisone shots, therapy. I still hurt, but can live. When all this started we were told by lawmakers and DEA we would not be messed with. But we are. I have seen friends i went to school with lose access to medication because the dea shut down a dr, they had no choice but to go to heroin. A lot are now dead. I put that on every person who is starting war with drs. Give us access to narcan, educate patients and let us live with a decent quality of life.

      https://www.cdc.gov/drugoverdose/data/overdose.html

    • Hi William
      My data also came from the CDC https://www.cdc.gov/drugoverdose/epidemic/

      Believe it or not I am a physician and agree with everything you mentioned except that my data is wildly inaccurate. Everything I have written is from ASAM, CDC, or FDA. As a government policy limiting opioids is incorrect therapy. More people have died because of it. Really CDC says 91 people die a day.

      I propose we continue to give opioids to patients and also promote everything you recommend plus enhance cognitive behavioral therapy. Treating pain as in treating addiction is very complicated, time consuming and most importantly expensive. CDC says it costs us Americans $78.5 billion per year. https://www.cdc.gov/media/releases/2017/a0315-business-pulse-opioids.html

      Let’s spend a little to save lives.

      Best
      JH MD

Recommended Stories

Sign up for our biotech newsletter, The Readout

A guide to what’s new in biotech — delivered straight to your inbox every weekday morning.