New Drugs With High Abuse Potential More Likely to Be Approved and Go to Market to Treat Pain

Summary: Study reveals 27.8% of pain medications with high abuse potential make it all the way through the development process, compared to only 4.7% of medications with lower potential for abuse.

Source: American Society of Anesthesiologists

“Despite the prevalence and societal costs of pain in the United States, investment in pain medication development is low, due in part to poor understanding of the probability of successful development of such medications,” said the authors of a  study published in Anesthesiology.

“The opioid crisis has highlighted the need for new therapeutics with low abuse potential to treat chronic pain,” they said.

“While pharmaceutical companies recognize this need, because of the subjective nature of pain … the conduct of clinical trials for new drug approval is a lengthy and costly proposition.”

According to the authors, a better understanding of the probability of the successful development of new pain medications would reduce some of the investment risks.

In the retrospective study, Dermot P. Maher, M.D., M.S., M.H.S., assistant professor, John Hopkins University School of Medicine, Baltimore, and financial engineering colleagues at the MIT School of Management analyzed 469 pain pharmaceutical development programs involving 399 unique active pharmaceutical ingredients between 2000 and 2020.

They used publicly available clinical trial metadata from databases provided by Informa Pharma Intelligence to determine the probabilities of success, duration, and survivorship of the pain medication development programs.

The study found that 27.8% of drugs with high abuse potential made it all the way through the development process, compared to only 4.7% of new drugs with low abuse potential.

Although the number of drugs with high abuse potential being developed has decreased since the peak of the opioid epidemic in 2010, they are more likely to successfully complete the development process and receive regulatory approval than medications with lower abuse potential.

“The higher probability of successful development could represent a more thorough biological understanding of pain signaling pathways targeted by medications with high abuse potential compared to the novel mechanisms offered by alternative medications with lower abuse potential,” they said.

“The opioid crisis was a wake-up call for medicine as a whole,” said Dr. Maher. 

“On the one hand, we had patients who were simply asking for their pain to be addressed. On the other hand, physicians had very little in their pharmaceutical toolbox that was either remarkably effective, non-addictive or lacked major side effects.”

It’s important to recognize that it is possible to successfully develop pain medications, he noted. “We can increase our understanding of pain mechanisms and target the development of new pain treatments to address this unmet medical need,” said Dr. Maher.

In an accompanying editorial, Michael S. Sinha, M.D., J.D., M.P.H., and Kelly K. Dineen Gillespie, R.N., J.D., Ph.D., echo Dr. Maher’s support for more development of pain medications with better safety profiles. Federally funded research must be conducted to learn more about the biology and mechanisms of pain, they said.

“The National Institutes of Health (NIH) and other research sponsors must allocate funding toward the development of safer analgesics and nonpharmacologic pain management strategies,” they state.

The study found that 27.8% of drugs with high abuse potential made it all the way through the development process, compared to only 4.7% of new drugs with low abuse potential. Image is in the public domain

“Expanding support for the NIH Helping to End Addiction Long-term (HEAL) Initiative is one way to achieve this goal.”

Changes are also warranted, they assert, “in public and private financing models to encourage and reward interdisciplinary, multimodal, and time-intensive pain treatment programs – programs that are highly effective in enhancing well-being and function but currently scarce in a system that continues to reward fragmented and intervention heavy care.

“Investment in cross training for providers in pain medicine, substance use disorder treatment, is needed as well as trauma informed care. Innovative, noninvasive biotechnology also holds promise.”

To change the trajectory of pain management research, they conclude, “concerted action by key private and public stakeholders across multimodal treatment domains is the best path forward.”

Learn more about the NIH Heal Initiative, a trans-agency effort to combat the opioid crisis by speeding up scientific solutions.

In addition, access information from the ASA about opioid abuse as well as alternatives to opioid treatment.

About this pharmacology and addiction research news

Author: Theresa Hill
Source: American Society of Anesthesiologists
Contact: Theresa Hill – American Society of Anesthesiologists
Image: The image is in the public domain

Original Research: Open access.
Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020” by Dermot P. Maher et al. Anesthesiology


Abstract

Estimates of Probabilities of Successful Development of Pain Medications: An Analysis of Pharmaceutical Clinical Development Programs from 2000 to 2020

Background

The authors estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. The authors also consider the effect of the perceived abuse potential of the medication on these variables.

Methods

This study uses the Citeline database to compute the probabilities of success, duration, and survivorship of pain medication development programs between January 1, 2000, and June 30, 2020, conditioned on the phase, type of pain (nociceptive vs. neuropathic), and the abuse potential of the medication.

Results

The overall probability of successful development of all pain medications from phase 1 to approval is 10.4% (standard error, 1.5%). Medications to treat nociceptive and neuropathic pain have a probability of successful development of 13.3% (standard error, 2.3%) and 7.1% (standard error, 1.9%), respectively. The probability of successful development of medications with high abuse potential and low abuse potential are 27.8% (standard error, 4.6%) and 4.7% (standard error, 1.2%), respectively. The most common period for attrition is between phase 3 and approval.

Conclusions

Our data suggest that the unique attributes of pain medications, such as their abuse potential and intended pathology, can influence the probability of successful development and duration of development.

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  1. Prescriptions of pain meds didn’t cause the opioid crisis. Illicitly manufactured Fentanyl did. This is pressed into FAKE pain pills, mixed w Heroin,methamphetamine, cocaine & more!
    Pill Mills & internet drs/pharmacies shut down by 2009.
    Workman’s comp, insurances, disability started this! Genocide to rid of weak & non-productive citizens. Sound familiar? Germany? Then PROP joined in, somrine who never treated pain but had $$ invested in Phoenix house addiction centers. Follow the $$ & the lies.
    Less than 2% addict to meds, addiction is predisposed! Alcohol doesn’t cause alcholoism anymore than water causes drowning!
    RX at a 20 yr low, yet ODs all time high! Illicit fentanyl is poisoning people! More people using street drugs due to being cutoff & abandoned by Dr’s in pain mngmnt. People once functioned full time jobs w a RX thst worked for THEM
    Now if yoy do get a RX, it’s the same as others. There’s no individualized care!! Stay out of my dr appt! This is between me & my dr. People need help controlling pain & quality of life! Suicides are on the rise! This is all so unnecessary! Millions do very well on RX w no issues for 30 yrs,there’s your studies! No Long term study on opioids has ever been completed. There’s a reason we all have natural opioid receptors & morphine in our bodies.this is not a coincidence. Wake up & educate yourselves,this is a war on injured, sick & disabled! Ev we ry person is one vehicle accident or work injury or diagnosis away from a lifetime of pain! Hope you are not next! No one asked to live this way.

  2. It’s not about the person in pain..but fattening pockets..why give a pill that is extremely affective in treating pain..at the same time puts you in the mood to weather the depression and anxiety you feel because of the Chronic pain..AND..

    Since when is EUPHORIA…a bad thing? So someone in chronic pain does not deserve a emotionsl or mental escape?..to feel hopeful..things are better now?.. that they can fear not to do for that moment what pain normally stops them from doing?!.. example..standing or sitting washing dishes..like me..i cannot stand long nor sit long..i lost my doctor that gave me my prescription for hydro..i have dishes over a year piled up my apt loaded with trash..severe chronic pain ..not at proper weight for hip and back surgery..cannot.move to exercise or therapy because of pain to loose weight to get surgery and the weight of depression..prior i was able to manage my pain..and was on my way to recovery…when mg doctor had to retire…i have tried over a year so far i was declined norco by pain management clinics..norco offer barely any serious side affects..you list ADDICTION..as a serious side affect…addiction to stupidity is far more dangerous..you people would rather give a patient tramadol..look up side affects..than hydro codone…so you then want to give a pill for pain..with 40 side affects..and a pill for depression and anxiety..another 40 side affects..what are the odds of a patient surviving without the need to battle various other side affects because of their chronic conditions…and dying in the process??…

    Have any of you crapped blood..i had to actually figure out how to stop my internal bleeding from what i found out was from taking methylprednizone..naproxen and nsaids… actually a simple natural oil stops gi tract bleeding fast! Natural stuff..opiod is natural and waay safe…so a few doses of pills you would rather push a day…also caused me extremely high blood pressure..blurred vision..swole up like a puffer fish..when all is needed was one extended release norco..and a couple Tylenol when needed..why not go after alcohol..tobacco..Norco is not the problem..lazy people who are not in the situation of their patients are. Opioid are not abused by all who take it..it needs to be openly prescribed for those who qualify to have it..monitor yes..but stop making patients feel like criminals if they say Norco works and they just need that..thats what it was intended for from its creation in the military..for severe chronic pain..you are intentionally causing great harm to patients like me having to resort to endless pills to easy my pain because u am told I can’t have the one pill that works because I might get addicted?!.. but when I tell them..but daily I an taking 7 asperins with methylprednisone on some days and others I take 3 rounds of 3 aperins with one meloxicam and I switch off..THEY SHOW NO CONCERN!…but the moment I mentioned. But when I was given hydro the have this scorn and oh we can’t give that! That’s addictive..and you wonder why people self medicate..overdose..mix the wrong things and end up in a crisis because of your gamed and denying what you know works well..in favor of what you don’t know will work well or not..we will know by how many people dies..there are billions of people..it us to be expected there will be millions of idiots with addictive issues..

    We all have addictions..no one doesnt…it’s just a choice of addiction..you tell me not everyone has addictive tendencies and I will show you a liar…

  3. These people are so right. My husband can only walk half a block before both hips start hurting and he needs to keep stopping to be able to get home. He was getting opids from the VA. Only used it when going out to walk. When this bs started about the opids, they wouldn’t give it to him. He’s a Vietnam vet, heart transplant recipient with multiple medical problems. He’s so done with these doctors. He’s fine to over 8 orthopedics and they can’t find anything wrong with his hips or his back. Many epidural with no help. The CDC and whomever else is involved need to listen to the patient. He’s 74 and has no desire to continue living in pain.

  4. I am a 77-year-old Lady and Have been taking oxycodon 15mg 3 times a day for about 2 yrs. Before that I was on Oxycotin for about 5 years for all the Arthritis I have in in every joint in my body my Dr. says its for Moderate Pain. But Let me tell you that when I used to be 5ft 11inches in high school and now at 77-year-Olds im only 5ft 1 and can’t stand up straight for the last 3 years. It is Extremely Painful when I get up in the morning until I can take my 1st pain pill and have my breakfast. I have to have a Health Aid 3 days a week and my Granddaughter helps me other days when she’s not working, I live alone in a Senior Apt Building,I use a walker and a Power Chair to get around. But now my Insurance company wants me to see if my Dr. can find me and Alternative Pain Med That Would Just As Good. But He Has Told Many TImes That Oxycodon Is The Only Thing Thing That Will Help Control My Pain. Oh I Am Also On Zarleto 20 mg Blood Thinner.He doesn’t even want me to Tylenol if I can possibly not take it.

  5. I was diagnosed with RSD now known as CRPS in 2008, in 2019 I gained a diagnosis of Central Pain Syndrome from neuro. I also gained a diagnosis of Sjogrens syndrome from rheumatology and a diagnosis of Adult Onset Tourettes from neuro. Then earlier this year I gained a diagnosis of Adrenal Insufficiency from endocrinology along with my already existing diagnosis of insulin dependent diabetes (approximately circa 2019). In April my neurologist informed me that from the untreated and then later undertreated CRPS, plus the pain from the central pain syndrome likely caused damage to enough neural pathways (and of course I have a diagnosis of Asperger’s syndrome so I’m already in the category of being not neurotypical) to trigger the Adult Onset Tourettes diagnosis, along with this piece of hated gold, because of the existing damage to my neural pathways and then with how long it took to get a diagnosis of Adrenal Insufficiency and then started on treatment for that, I am now classified as having non trauma induced traumatic brain injury (or rather neural pathway destruction).
    Since all of this info was told to me, my endocrinologist and neurologist have informed my pain management provider that due to levels of damage to nerve pathways (especially in my brain) but also throughout my body, it will NOT BE ETHICALLY WISE OF THEM to cut me from the opiate that I’m on currently.
    In fact, I just got out of the hospital who happens to have a feature in their medication record system that dumps class 2 medication orders after 72 hours and the night nurse I had on my last night in the hospital is considering bringing up ethic violations against the attending who was covering for the attending that gets assigned to my care for not continuing the pre-existing order of oral 4mg dilaudid available every 6hrs (what my pain management provider has me on at home) and instead opted to have an order placed for 4mg IV morphine every 6hrs prn. I feel bad for what I did to my nurse because of the level of volume of agonizing screaming and absolutely ugly crying from me that she was then left with high pitched ringing in her ears. I believe that it was so bad, I vaguely recall hearing my nurse and her charge nurse questioning whether they should reach out to the code team (the team that rushes to those in respiratory distress/cardiac arrest) to have me rushed to the ICU and put on a drip of propofol and on a vent until the regular attending could be reached to decide on my care.
    So, now hearing that drugs with risks of even higher abuse rates could be approved to come onto market definitely worries me. I’m not entirely sure that any more drugs with chances of higher abuse for any condition should be approved much less come onto market.

  6. Due to a 13 hour botched lumbar fusion I entered pain management at age 34 in 2002 and became disabled because of the oxycontin I am taking. I could still function at work but the stigma of opiods is why I was let go. With the 2016 cdc guidelines and my doctor retiring in 2020. I’m now taking 25% of what I was taking for all those years. I functioned without side effects and now I’m mostly immobile as the low dosage and injections do not help much. The cdc needs to let legitimate doctors do their jobs and give us the meds to function. This is terrible that we cannot get help because someone else abused drugs.

    1. I recently read where the dea/fda & the others who think they know best..refuted the claims of physicians of very strict guidelines saying that they could use their discretion. That the Docs themselves were the problem.All I know is I cannot function most days because of pain. People need to see blood to understand pain. Peace ✌

      1. CDC along w DEA created 2016 guideline and now revamping them after admitting that they were misapplied! They weren’t intended for chronic pain patients, but CPPs were affected the most! Many have committed suicide due to untreated pain.
        Illicitly manufactured Fentanyl caused deaths by poisoning! Never was a RX issue. CDC & DEA have admitted this. 7 yrs too late. Danage is done. Dr’s are in jail for helping patients.
        Pill Mills have been gone for 14 yrs already.
        This must end! Contact your legislators, medical boards, etc see American Pain & Disability site. And others.

  7. My pain has turned me into a monster, and I have developed a violent hatred of medical doctors and nurse trashtioners who are too chicken shit to prescribe pain medication to people who are suffering.

    1. Joe, I hear you and understand.What I hate is always being edgy and deceptive, afraid my meds will be taken away. I know longer enjoy “euphoria” of the morphine LL but the reduced pain allows me to work to feed my wife and I. I am 79 yrs old. They will take our effective pain meds sooner than we think. Matter of time. Ty

  8. The government in Washington needs to mind their own business. Stay out of peoples personal lives. People in pain need relief. Why aren’t non addictive drugs like Ecstasy allowed to be purchased? Politicians are all on power trips.

  9. I suffer with pain in my right shoulder due to having 3 surgeries. I don’t know what to do or where to turn to because of the stigma of pain pills… Not everyone who uses pain meds for legitimate pain becomes a junkie..
    Warm regards,
    Jeffrey Hardin

    1. The word junkie is not proper. The sad situation is that there is a crisis. These medications are addictive & being abused by physicians themselves. Address your pain differently. There are new developments for pain management. Seek medical advise.

      1. Yes, there is an opioid crisis. No, not every physician abuses these types of meds. And no, not every pain patient does either. Educate yourself.

        1. The REAL crisis is prohibition of narcotic analgesics for chronic pain. People can’t comprehend how this is unless they’re affected. They say stupid things out of ignorance. They couldn’t do our “lives” for a week.

      2. You CLEARLY do not suffer from chronic pain from osteoporosis, osteoarthritis, gout, and add two heart attacks, hypertension and hypothyroidism ALL AT THE SAME TIME or you would not make such an ignorant statement. Physical therapy, heating pads, and ibuprofen can only do so much – actually very little. I hope you NEVER experience what I live with daily. We’re it not for my narcotic I have taken responsibly for 16 YEARS, I would be bedfast most days.

  10. I’m a chronic pain patient & my pain was left untreated for21/2
    Yrs.Pain Mgmt groups are a joke as is their contracts & mental health.Just because I use opioids to control my pain doesn’t mean I’m an addict.Im already treated like a criminal & how stronger drugs will fix that I don’t know.Its just another way to try & control those that do
    Not need to be while the real addicts are treated. Since when is a genetic inherited disease like rhuematoid issuses from 4 gene.’s the basis of addiction.

  11. At the age of 44, it is nearly impossible to be treated with respect. Often I feel the 1994 disability rights act has never been read by anyone in this vicious cycle. The “Health Care System” is neither healthy, nor caring or a system.
    I’m less worried nor impressed by the constant need we have to “save” individuals. More harm comes to those who truly need pain medication. It’s a gross feeling being disabled at 40 yrs old. That feeling is important. This is not news. This is propaganda. That is my opinion. That Masters Degree in Literature/History & 20 yrs massage therapist…that’s me. So when I say I need “xyz” … I expect to be treated with respect. I’m not impressed by fluff. Understand you report the news & have obligations. Maybe hire someone like myself who could move your readers emotionally. People are tired of “new” this & FEAR.
    Gotta go with the tide & stand tall. Our effort has no “new” approach. We need more people with experience. Life is painful & it’s difficult to tell “free democratic americans” that they are free when health care is a system that serves the rich. You’re welcome to serve your “new” to those who are always looking for help…the poor, the disabled…
    I have to talk to a doctor/pharmacist every 18 days because I’m treated with dignity & respect. The times they ain’t never change✌🏼

  12. As someone who has dealt with chronic pain due to surgical adhesions for over 25 years now and never snorted or smoked/abused any medication, just tried to function on a daily basis with type 1diabetes for 47 years I’m a perfect example of how much the junkies that created the opioid crisis have had a huge impact on my quality of life and the diabetes. If I fight for pain management I’m seen as a addict. Yet if I eat- a huge part of controlling the diabetes I spend the next day or longer in pain that has brought me to tears and ready to just give up. I’ve bought lock boxes to keep my medication in, never failed a pill count, and never needed any intervention for overdose. Yet 5 years ago I was dropped by my pain management provider after the state threatened to take her license if she treated any more pain management patients. Since then I have developed more complications from the diabetes that are taking my vision and causing nerve damage that will eventually lead to my death. With absolutely no help from my insurance company. All I want to do is be able to get out of bed in the morning and have a productive day. And at 56 I’ve considered suicide just to get it to end. Anyone have any answers for the people who are in this same situation??

    1. I have 2 broken vertebrae, a host of other degenerative issues, nerve damage into my legs and feet. Some days I can’t walk and am awaiting a double fusion the doctors hope will get me 70% to right but no guarantee. Mayo Clinic told me to take Tylenol and ibuprofen. I cry every day. I don’t sleep. I’ve contemplated suicide as well just to end it. My quality of life is nowhere near what it was. States are providing needles and safe spaces for addicts but I can’t get adequate pain management. I had to resort to medical Marijuana just so I can sleep but I can’t use it every day because I need to function and I can’t afford it!

    2. You should probably try to enroll in a diabetes type 1 study on islet cells transplant, they’ve conducted it on mice already with great success. From what I’m seeing, curing this type of diabetes has some hope with the recent efforts of scientists. As for the pain, I’m having it everyday too due to autoimmunity, and I use natural anti inflammatory supplements, plus acupressure, plus electric vagus nerve stimulation.

  13. Interesting. I have problems with many off label pain medications, intolerance or sensitivity’s. Example, brand name Cymbalta, pushed my BP up to 102/210. Just one tablet.
    I find I get most benefit from Mersyndol. The one with codeine. But it’s not the codeine, it’s the relaxant that offers the most benefit. Problem for me is that I already take the maximum amount of Panadol each day, Panadol osteo.
    Valium is too strong, the lowest dose, I break it into bits and just take an equivalent of 1/4. But it still leaves me a bit groggy. I can take 1/2 a Mersyndol and be fine. I’ve been on Tramadol, my serotonin levels rose, Targin, works on part of my pain, but my oxygen levels are reduced. Ibuprofen is good, but it affect my BP. I’m now on BP medication, but not sure if it’s needed if I stop Ibuprofen. After more than 10 years on this horrible journey I also now have gut problems. Heartburn and really bad stomach cramps. I’m ever hopeful of a new medication I can take without the stigma and addictive properties. Although I can increase and decrease my Targin without issue. Endone too.

  14. Why is the unsubstantiated link between legally prescribed pain medicine and abuse continually perpetuated? During the 1990s there was a spike in abuse of oxycontin but most abuse now is people illegally using heroin or fentanyl, not chronic pain patients. The hoops needed catch 99.9% of abusers and as for the rest? Chronic pain patients use their medications for years for a reason, they work and now we are all fully or partially bedridden because our medication was taken away for no good reason, no abuse, no failed pain contracts nothing and now we suffer. Please at least publish the other side of this argument instead of the propaganda of the government who are not doctors and are not directly dealing with this issue.

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