Central nervous system is hard to treat: A new neuropsychiatric drug typically takes 18 years to go from lab bench to patient.
Image: Gary Carlson Photo Researchers, Inc.
-
The Best Science Writing Online 2012
Showcasing more than fifty of the most provocative, original, and significant online essays from 2011, The Best Science Writing Online 2012 will change the way...
Read More »
Schizophrenia, depression, addiction and other mental disorders cause suffering and cost billions of dollars every year in lost productivity. Neurological and psychiatric conditions account for 13 percent of the global burden of disease, a measure of years of life lost because of premature mortality and living in a state of less than full health, according to the World Health Organization.
Despite the critical need for newer and better medications to treat a range of psychiatric and neurodegenerative diseases, including Alzheimer’s and Parkinson’s, drugs to treat these diseases are just too complex and costly for big pharmaceutical companies to develop. The risk of spending millions on new drugs only to have them fail in the pipeline is too great. That’s why many big drug companies are pulling the plug on R&D for neuropsychiatric and other central nervous system (CNS) medicines.
Our team at the Tufts Center for the Study of Drug Development has arrived at this conclusion after conducting surveys of pharmaceutical and biotechnology companies about the drug development process. These surveys allow us to generate reliable estimates of the time, cost and risk of designing new drugs. Our analyses show that central nervous system agents are far more difficult to develop than most other types.
One of the problems with neuropsychiatric drugs is that they take so long to develop. A CNS drug, we have found, will spend 8.1 years in human testing—more than two years longer than the average for all agents. It also takes more time to get regulatory approval—1.9 years, compared with an average of 1.2 years for all drugs. Counting the six to 10 years typically spent in preclinical research and testing, CNS drugs take about 18 years to go from laboratory bench to patient.
Few compounds survive this gauntlet. Only 8.2 percent of CNS drug candidates that begin human testing will reach the marketplace, compared with 15 percent for drugs overall. Failures also tend to occur later in the clinical development process, when resource demands and costs are at a peak. Only 46 percent of CNS candidates succeed in late-stage (phase III) trials, compared with 66 percent on average for all drugs. As a result, the cost of developing a CNS drug is among the highest of any therapeutic area.
What makes these drugs so risky? Assessing whether or not a candidate for, say, a new antibiotic works is relatively straightforward—either it kills the bacterium or it doesn’t—and a course of treatment typically lasts a few days, which obviates the need for long-term testing for safety and efficacy. CNS compounds, in contrast, have it a lot tougher. It is difficult to judge if a reduction of schizophrenic episodes or a cognitive improvement in Alzheimer’s patients is the result of a drug or a random fluctuation in the patient’s condition. Treatment periods can last as long as a patient’s lifetime. It is no wonder success rates are low.
Some help is on the way. The Coalition Against Major Diseases, made up of government agencies, drug companies and patient advocacy groups, has developed a standardized clinical trials database that will allow researchers to design more efficient studies of new treatments, initially for Alzheimer’s and Parkinson’s. President Barack Obama’s health reform law also contains several provisions that could provide incentives for innovation in areas of unmet medical need. One is the Cures Acceleration Network, which authorizes the National Institutes of Health to help academic researchers screen for promising compounds. Ultimately, making new CNS medicines may depend on a networked approach to innovation, in which many organizations share in the risks and the rewards. It is clear that the challenges of developing new neuropsychiatric medicines are greater than any one company, institution or organization can bear alone.
Disclosure: The Tufts Center for the Study of Drug Development is funded in part by unrestricted grants from pharmaceutical and biotechnology firms.
This article was originally published with the title A Dearth of New Meds.
Already a Digital subscriber? Sign-in Now
If your institution has site license access, enter here.
Rights & Permissions
See what we're tweeting about
15 Comments
Add CommentEven though the disclosure pretty well sums up the point of view of the authors, this article still seems a little disingenuous. Polling Big Pharma and Big Device about their problems isn't going to generate anything more than the usual whiny complaints about how hard they try, how much they spend, etcetera. The fact is that some of the referenced billions are penalties (Pfizer 2.3 of them and counting) or fines for outrageous and/or illegal behavior. The truth is that public health outcomes would probably be improved if the rush to market and attendant shenanigans were delayed even longer - Seroquel's use as an instrument of pacification in nursing homes and juvenile detention facilities and the off-label Neurontin debacle being cases in point. The comparison with antibiotics is also a little suspect. Currently there are fewer than twenty in the pipeline and none address the new mutations in gram negatives - a looming public health disaster. The reason - not enough profit. It's time that the universities cut loose from corporate interests and approached the NIH with basic research proposals rather than supporting the duplicative development of yet another CNS hammer. We need a fundamental shift in how research is conducted and supported, one that is not wagged by the stockholder tail and is responsive to the health needs of the U.S. We pay more than any other country for health care and consistently rank in the 30's behind all of the other industrialized and some of the not so industrialized nations, in terms of the WHO health indicators. Some of this is our disgraceful collective inability to address issues of socio-economic status, some the excessive and wasted sums on yet another variation of inadequately executed and sometimes fraudulently reported research. It's time for a change - to expect it to come from a consortium of self-interested players is naive at best. I'm looking forward to the day when I can get the most current health news from a health or science section of the NYT or WSJ instead of the business sections where yet another transgression is reported.
Reply | Report Abuse | Link to thisWhy does the article ignore Multiple Sclerosis (133-240/ 100 000) which has a higher prevalence in Canada, England and the United States than Parkinsons (13.4 / 100 000 )? And it strikes younger adults much more commonly than Parkinsons. Average age of onset for MS is 15-40 years of age. So we have to live with this disease for much longer period of time than those with Parkinsons or Alzheimers. Most with MS must quit jobs or education usually 3 to 4 years after diagnosis.
Reply | Report Abuse | Link to thisThere is one drug that is very effective and is completely ignored (cannabis).
Reply | Report Abuse | Link to thisThe trouble at present is, we have immoral governments and pharmaceutical companies that refuse to accept that cannabis is beneficial to the human population.
>>>Drugs to treat neuropsychiatric disorders have become too risky for big pharma<<<
Reply | Report Abuse | Link to thisThe title says it all. Valproic Acid leads to autism features in the fetus. What are the long term consequences of drugging Americans? We will see in this generation, especially interestingly in their offspring. Oops...
While the comments subsequent to apirie are all valid, that f1rst comment nails the basic issue, problem and solution. Compare this to NYTimes August Opinion piece by EZEKIEL J. EMANUEL, "Shortchanging Cancer Patients".
Reply | Report Abuse | Link to thisUnfortunately, the NYTimes piece does not come as close to the accuracy of the solution or the cause of the problem as does apirie's: Greed is taken to be the total rationale and justification of "research".
Do you want an MBA deciding your child's fate based upon the size of their bonus?
Gee, thanks for the pharma advertisement posing as an article. Nice
Reply | Report Abuse | Link to thisThe article completely fails to point out the extreme
Reply | Report Abuse | Link to thisover use of the existing medications. I know as many if
not more people harmed by psych meds as helped. Generally
strong meds given for fairly minor problems.
Notice the "could you be depressed" ads that pop up
every where? If you need an online quiz to tell you
your depressed, you don't need drugs! You may need
some exercise or other more gentle help.
The drugged up population is not smiling. Buddhist monks
are, the human race already knows how to treat
unhappyness, but its just not profiteable to do so.
...destroy the few working brain cells you have left.
Reply | Report Abuse | Link to thisThat cures everything.
Big pharma, just like all big corporations, are driven primarily by short term stock market profits. With a 18 year lead time, and not many good leads to follow at present, big industry is doing what it has often done in the past, wait for big government to fund public (i.e. university and foundation) research into neurological and psychiatric diseases. For so long they have been following the "me-too" process of drug development, following up on successful drugs by duplicating their mechanism of action with analogous or similarly acting drugs - thus leading to nothing new but subtle changes in potency and side effect profile.
Reply | Report Abuse | Link to thisIt is this lack of new ways to attack old problems that lead to things like the gabapentin (Neurotin) debacle, using a relatively not-toxic drug to treat everything from excessive complaining to farting impolitely.
I don't really see how this is an advert for big pharma. They obviously gain no credit from an article like this. An unrestricted grant means the foundation can do whatever they want with it.
And complaining that MS is not mentioned is like whining that your favourite deck chair was not rearranged on the titantic. It is an obviously non-inclusive list of diseases.
As someone who has lived with depression and whatever flavour of the month illness they want to label me with, I have been through the pharmacopia, and as a psychopharmacologist, I have been through my own list of possible treatments, albeit non-approved. They all have deficits in terms of outcome, side effects, and none of them were great. I hated every time I had to give half my paycheque to pay for my meds. I agree that something is not right in the way drug companies operate. Luckily, I live in Canada, where my government covered the cost of a therapist to help me help myself. The main problem in the US is the health care system itself, leading doctors to rely on drugs as panacea and not looking for the real problem.
By the way, the prevalence of Parkinson's that I found is in the same neighbourhood as MS, between 125 and 300 per 100,000
Reply | Report Abuse | Link to thisI know several parents of autistic children and none of them have ever used valproic acid. Your post is woefully incomplete and lacking support by reliable sources.
Reply | Report Abuse | Link to thisSorry to poo in your pudding but there is quite a bit of evidence that pot use damages the brain rather heavily. Perhaps a processed form may help but who knows? I have no problem with legalizing pot so we can tax the snot out of it but it isn't a magic cure all any more than anything else is.
Reply | Report Abuse | Link to thisHm. Research and marketing should go to better medications for people with psychiatric disorders, it saves time money and makes life better for everyone. But, I also think that this is an opportunity to find some alternative and more innovative ideas to help people move forward who struggle with the stress of mental illness. Someday there might be a long lasting cure--I hope we do find a cure someday for disorders like autism, depression, bipolar, schizophrenia... those are the major disorders that when without medications a lot of people would be at serious risk. I assume many of the people bashing this article haven't suffered from a major disorder and don't know much about what it's like.
Reply | Report Abuse | Link to thisMaybe other newer chemicals could be used to help with stress, pain, creativity, repairing cells, and memory.
In the wrong hands, it could be disastrous. Anyways, we don't even seem to have the right to a fair trial anymore as citizens, so why bother buying medications and investing in something with potential.
To understand the issues that are presented here I would suggest some personal research, before coming to any conclusions. In this regard, I would recommend, the book Mad in America, by Robert Whitaker.
Reply | Report Abuse | Link to thisThat being said, there have been serious questions raised as to the effectiveness, and safety of the current crop of psychiatric medicines. Most do very little, all most all of them create the very symptoms they were designed to treat. And despite years of pharmaceutical propaganda that psychiatric drugs treat bio logical problems with brain functioning, there has never been any conclusive proof of this. It is not a fact it is a theory only.
But In fact, drugs like Clozapine (Clozaril) banned in Europe for producing symptoms of agranulocytosis, but marketed here because of the growing failure of the previous generation of neuroleptics, have been shown to trigger schizophrenic like symptoms in patients. After a first exposure, the brain develops what is called D2 sensitivity, the next exposure results in full blown psychosis.
There is a growing awareness that this generation of neuroleptics may be responsible for many of the mass episodes of violence here. Young white disturbed males from relatively affluent families, are at high risk for these symptoms. Some believe it is because they are able to afford psychiatric treatment, because they are covered under insurance, when others outside their demographic are not.
That many so called neuroleptic medications, trigger manic episodes is well documented. They after all carry a black box warning, for just those concerns.
What is not well understood by the public as that many of the university funded research programs that are used to evaluate these medications, are funded by drug companies.
The insurance companies as well, don't wish to pay for talk therapy any longer, because it reduces their high profit margins. The present generation of psychiatrists have obliged them. Without medications, they would have very little to offer.
Hence they are more than willing to prescribe dangerous drugs, to people that could be better treated by other means. Witness, the fact that prescription medications, are now the leading cause of drug over dose in this country, surpassing drugs like Heroin.
Unfortunately, mental health coverage is controlled psychiatrists, which may lead to the collapse, of our mental health system once the public is better informed, alternatives are needed instead.
A famous WHO study showed, this country had worse treatment outcomes than Nigeria.
Everyone posting in this thread will need drugs one day.
Reply | Report Abuse | Link to thisI can tell you that availability of even basic drugs is becoming an issue. Backorders and restrictions are limiting what we give.
I don't foresee a great improvement. We will likely continue to pay higher prices for the drugs we do get so that nations with socialized medicine can get huge discounts on their drugs.
We will likely see fewer drugs available due in part to Pharma not manufacturing some older drugs that are not profitable but are necessary to clinicians.
Stay healthy. And toughen up, because if you think Obamacare is going to pay for anesthesia for every procedure that people want anesthesia for, you are mistaken.