A Fix Special Report—The Maddening State of Addiction Research Funding
A Fix Special Report—The Maddening State of Addiction Research Funding
In Virginia, a small company has developed a serotonin blocker that deters alcoholics from wanting to drink. It sits on the shelf awaiting funding for its next level of required testing.
In California, as The Fix reported earlier this week, a vaccine for heroin addiction that in animal tests completely blocks the drug from reaching the brain, languishes in the laboratory without support.
Meanwhile, research funding for hugely promising alternative addiction treatments such as neurofeedback technology and NAD (massive doses of a Niacin derivative) is barely in the game. And forget about promising studies of socialized animal and human behavior modes that tend to prevent addictive behavior in the first place. Or deeper research into tobacco addiction, or validation that drug harm-reduction programs seem to be working so well in a NYC non-profit rehab center.
Most of us understand that substance addiction and alcoholism is a major social, health, and economic issue. The costs to the economy alone in health care, productivity loss, crime, drug enforcement and incarceration are estimated to be more than $500 billion a year - and that number is from a study ten years ago. In response, only a tiny percentage of this is spent every year by all players - government, private Pharma companies and foundations - on developing and testing a variety of would-be miracle cures (or even just helpful medications or processes).
In the substance abuse funding game there are gamemakers - those who decide which projects are worthy of the awarded dollars - and competitors: researchers vying for limited funds. The gamemakers come from the public and private sector and ultimately determine whether a competitor moves forward or gets denied.
This article is an inside peek at how that game is played and who gets to be the winners and who the losers.
THE BIG PICTURE
First, it’s folly to think that every brilliant idea gets funded. What’s more, it may take decades for a scientist’s theory to take flight. Some projects, inventions or new discoveries will forever remain scribbled tomes given the realities of how the human species wants to spend its money.
According to the report "Ending the Drug Wars," released May 7 by the London School of Economics Expert Group on the Economics of Drug Policy, “In spite of a significant body of evidence that drug-related health services are a very good investment for society, they remain woefully underfunded and unavailable.”
In today’s cash-strapped research arena, it is the novel ideas that most often are relegated to the slush pile of the never-funded.
“Funding is in a bad situation," says Keith Humphreys PhD, professor of psychiatry at Stanford University. “The NIH (National Institute of Health) generally funds about 90% of all the world’s addiction research. And the NIH is straining under the fiscal environment. It’s particularly tough for younger investigators when there is a decrease in available funds.”
Statistically, with epidemics of addiction to heroin, meth, prescription drugs and designer drugs playing havoc in various areas of the country, much less the world, there has never been a greater need to fund innovative research and novel concepts related to substance abuse. And there’s the rub. With much at stake in the research funding game - careers, political policies and amounts of funding dollars - players from every quarter are struggling with each other for position and voice, including organization leaders, scientists, activists and politicians. As a result, conflicting ideologies, intense competition and narrowly held perspectives are holding research dollars hostage… and innovation at bay.
Let’s look at the federal programs. The largest, the National Institute on Drug Abuse (NIDA), part of the NIH, is working with a drastically reduced budget - 25% less than a decade ago. In 2013 researchers vied for their part of a $141.3 million actual 2013 budget. Until 2003 the NIH research budget was rapidly doubling but flattened out until 2008 when the Great Recession forced a dramatic tightening just as substance abuse was spreading. Demands for research dollars soon far outpaced what was available.
In this tight climate, NIDA has opted for caution and familiarity over innovation. Seasoned scientists have been given the advantage in competition, with a greater percentage of the purse now going to those with a solid research history, placing more dollars in fewer hands. “There is concern across the board in the research arena with a decreasing budget,” says Jack Stein, PhD, director of NIDA's Office of Science Policy and Communications. “There is no doubt: those with experience have a better edge…unfortunately wonderful grant requests have come in that could not get funded because of budgets.”
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has an even smaller budget: Out of 530 applications last year, 166 were funded for $55,291,978.
Some history: Federal money for research was plentiful after World War II. And until the 1980s, scientists found support and funding for novel ideas. Take Jim Topolski, PhD, research associate professor at the Missouri Institute of Mental Health, a unit of the University of Missouri, St. Louis.
Back in the mid-1980s Topolski worked for the Missouri Department of Mental Health. There was little competition for grants. While his first grant request - to study substance abuse services for the homeless - was not funded, his second, which was aimed at reducing waiting times for people with AIDS who needed substance abuse treatment, was awarded funding. Over the years he has been successful with many of his grant requests, especially with funds from The U.S. Dept. of Health's Substance Abuse and Mental Health Services Administration (SAMHSA).
These days Topolski, like others, finds himself competing for less money from both SAMSHA and NIH.
One drug hungry for financing is AD04, licensed by ADIAL in Charlottesville, VA. A serotonin blocker, it has shown in Phase II trials of 283 patients to dramatically reduce the craving for alcohol. AD04 was initially studied at the University of Virginia and University of Texas and funded through the NIAAA. Then ADIAL licensed the technology. “We’re a small biotech pharmaceutical manufacturer,” says William Stilley, CEO. “We raised under $10 million initially. We are ready to go into Phase III trials, and we are seeking funding.” Stilley says the company will most likely be a financial or strategic partner. “It is getting harder and harder to get funding.”
Those frustrated with research funding ask: what about funding more grants with less money? Would there be room for new ideas? Without it, what happens to innovation given that there is hardly a way for creative approaches to demonstrate effectiveness without funds to produce peer-reviewed studies?
The gorilla in the room around this question turns out to be the ideology of the decision makers. “There are ideological constraints tied to what gets funded," says Ethan Nadelmann, founder and executive director of the Drug Policy Alliance in New York City. An example? The tendency to fund "abstinence only" programs and the war on drugs at the expense of drug prevention research. "There is not a lot of evidence of what works because it does not get studied. Today, kids lose their drug virginity before their sexual virginity. What’s the needle exchange of today?"
FEDERAL TRIALS AND TRIUMPHS
NIDA is not without its successes. In its view, one of the most exciting, innovative areas of research it is currently funding is likely to lead to an intranasal delivery system for naloxone, an important medication that can immediately stop overdose. “This could be a huge advance in the area of harm reduction,” says a NIDA spokesperson. “Imagine a world where addicts or their loved ones could have (on hand) a user-friendly and nearly mistake-free delivery system to save a life.”
NIDA’s research spans complex neuroscience and cellular biology, the development of medications to assist in treatment and broad-based epidemiological studies. It also includes community-based research and initiatives intended to inform drug prevention strategies. There are more than 2,000 grantees around the world working in a wide variety of areas of research. According to NIDA, “Each potential grantee thinks his/her area of research is the most important; and, given the low rate of research acceptance across NIH in general, there are naturally many disappointed scientists who will not agree with how funds have been prioritized.”
In 2013, out of 1,874 NIDA applications, 365 were awarded grant money for a myriad of research goals. These included $25,000 to the International Cannabinoid Research Society in Winston-Salem, NC for sponsorship of the ICRS Symposium on the Cannabinoids and $615,063 to Johns Hopkins University researchers for the evaluation of the effectiveness of employment-based reinforcement to simultaneously promote high rates of Vivitrol(R) adherence and increase opiate abstinence.
On the other hand, examples of the unfunded include a nicotine addiction study by Brett E Froeliger, PhD, an assistant professor of Neurosciences at the University of South Carolina medical school. Dr. Froeliger studies populations particularly vulnerable to nicotine dependence, including individuals suffering from major depressive disorder (MDD) and post-traumatic stress disorder (PTSD).
Also unfunded was a promising New York harm reduction program. “Over the course of the past 20 years, we collaborated with NDRI, a research organization, to do follow-up studies on graduates of our successful ARRIVE program, one of the first in the US to employ harm reduction practices,” says Howard Josepher, LCSW, president and CEO of Exponents in New York City, a non-profit community-based organization dedicated to helping men and women suffering from the effects of substance abuse reclaim their lives. “I don't remember the specifics but our applications to NIDA were rejected.”
Although his early studies in the 1960s and 1970s showed great promise and an alternative view of addictive behavior, Bruce Alexander, PhD, a Canadian psychologist, was never able to secure NIDA funding or mainstream support to continue his Rat Park experiments. Dr. Alexander found that, when isolated, rats would consume large quantities of heroin, cocaine, or morphine. Then, when placed in a community of other rats, consumption dropped dramatically.
“When I talk to addicted people, whether they are addicted to alcohol, drugs, gambling, Internet use, sex, or anything else, I encounter human beings who really do not have a viable social or cultural life,” writes Dr. Alexander. “They use their addictions as a way of coping with their dislocation: as an escape, a pain killer, or a kind of substitute for a full life. More and more psychologists and psychiatrists are reporting similar observations. The view of addiction from Rat Park is that chronic isolation causes people to look for relief.”
THE COMPETITION TRIALS IN TODAY'S GRANTS
A NIDA or NIAAA grant application undergoes three levels of review. The first is the NIH peer review system, which is followed for all NIH institutes. At this level reviewers decide whether the application merits discussion by the larger committee. About 50% get a "no-discuss" at this stage. Other applications go on to NIDA’s Advisory Council. If an application makes it through round two, it is sent on for a third trial - a review by NIDA’s director, Nora Volkow, MD, who makes the final decision on the merit of an application for funding.
The overall success rate in 2013 for all NIH grant applicants, not just substance abuse researchers, was 17.8%. The success rate for NIDA was 19.5%, meaning that out of each 100 grant applications, 19 received funding.
NIDA takes issue with such claims. “We are basing our decisions on multi-step open calls for research and not focusing on specific outcomes,“ says NIDA’s Dr. Stein. “In peer review, good applications rise to the surface and in general we fund in priority order.”
WHO GETS THE MONEY?
Many in the research community would take issue with Stein, including at least one Nobel Prize winner.
“The system now favors those who can guarantee results rather than those with potentially path-breaking ideas that, by definition, cannot promise success," according to an essay published in April by four scientists, among them Harold Varmus, MD, Nobel Prize co-recipient and director of the National Cancer Institute.
The article, “Rescuing US biomedical Research From Its Systemic Flaws,” published in the Proceedings of the National Academy of Sciences, argues that the hyper-competition for resources to conduct science suppresses the creativity, cooperation, risk-taking and original thinking required to make fundamental discoveries. "Young investigators are discouraged from departing too far from their postdoctoral work, when they should instead be posing new questions and inventing new approaches,” wrote the four scientists. “Seasoned investigators are inclined to stick to their tried-and-true formulas for success rather than explore new fields.”
A denial of funding is a devastating blow to a scientist who spends many long hours researching, writing and revising grant applications. “I basically spent 20 years in science and developed a herpes simplex virus type II vaccine, but I’m a nobody at a no-name university,” says Bill Halford, PhD, an associate professor of microbiology at Southern Illinois University School of Medicine, Springfield. “In the NIH system, it doesn’t matter. I’m not important enough.”
The way Stanford's Dr. Humphreys explains it, the average age time it takes a researcher to obtain his or her first grant is nearly 10 years more than in the past. One consequence: after repeated rejections, younger scientists are leaving research. Most funding now goes to researchers who are over 60. In 1980 less than 1% of fundees were over age 65; today it is 7%. And in 1980, close to 18% of all fundees were under age 36; today it’s 3%.
“They don’t take a risk on new people. Certainly people retain creativity as they age but historically more innovation comes from younger researchers,” Humphreys says. “And it is not sustainable. Who will be there to study when those in their 60s and 70s are retired and the younger people have given up, particularly the MDs? They can make more money treating patients."
Occasionally, Humphreys notes, a small project from a younger investigator will get funded in an early stage. "But you lose programmatic continuity when a small study that shows promise gets funded and now you’re ready for the big grant and can’t get it, so the initial grant goes to waste.”
Has he been affected? “I’m in the fortunate group, it doesn’t mean it’s easy for me, but it is much easier for me versus a newcomer. It’s hard to get a leg up [especially] if you are at a state university or smaller college. Not at Stanford or Harvard or other established institutions.”
In Dr. Topolski’s lab, a reduction in funding meant a research group of 20 scientists was reduced to 8. And these days he no longer writes grants because he is so busy finishing grant projects left behind by retrenched researchers. Initially, Topolski says, when the funding crunch came he considered early retirement. He chose not to retire, he says, because he is getting to learn about new things with new partners. His most recent study, for example, is in collaboration with the Missouri Departments of Corrections and Mental Health, the St. Louis Drug Court and Alkermes, the company that manufactures Vivitrol, an injectable extended release naltrexone used for alcohol dependence and to prevent opioid relapse. “We are really blessed,” says Dr. Topolski. “We have visionary leaders.”
WHAT ABOUT NEW RULES FOR THE GAME TO BREAK THE IDEOLOGY TRAP?
Throughout history, those in power have ostracized new, alternative thought. Ideas first conceived as lunacy are often later viewed as genius. Consider Joseph Lister, Albert Einstein, and Galileo. There are scientists who argue that these geniuses would never get approved for a federal grant today because they wouldn’t fit into the strict criteria for an award.
The larger point here is that alternative ideas have positive consequences when they enter mainstream thought. One example already mentioned in the substance abuse treatment field is harm reduction - strategies that have proven effective in needle exchange programs and other areas such as minimizing but not eliminating drinking alcohol. “I really think it is problematic to only present abstinence to a 20-year-old,” says Sheigla Murphy, PhD, San Francisco. “My god, it’s so much part of their social life and culture and then we ask them to give it up forever. I think we need to put money into research for harm reduction.”
Dr. Murphy is a medical sociologist who has been researching various types of illicit drug use, violence, medical and drug treatment for more than 25 years. She has been the principal investigator of eight NIH grants and published numerous articles concerning heroin use, methadone maintenance, needle sharing, needle exchange, cocaine selling, natural recovery from drug use, drug users in health care systems and women’s drug use and pregnancy and violence. Her work has been seen in Addiction Research, The Journal of Psychoactive Drugs, Journal of Drug Issues, Contemporary Drug Problems, Qualitative Sociology and Social Science and Medicine
“I am lucky right now,” says Dr. Murphy. “I have two grants. So many new and seasoned are not getting funded.”
Murphy is among a growing number of dissenters who point to the inflexibility of today’s research funding environment. Many stress the importance of taking an epidemiological view in making grants and they cite a combination of limiting factors now controlling grant decisions and preventing an expanded research focus. These factors include outright prejudice, a drug war mentality, and temperance views.
“Barriers are based on prejudices and false beliefs perpetuated by a stigma so intense most can’t think of someone addicted to a substance as responsible,” says Josepher. “They are demoralized and vilified. The way I see it, people use drugs because they are in pain, they are in a negative relationship with self…if they are not in as much pain, they won’t need to self-medicate. Evidence equals research and for the last 50 years the research has supported a government policy of abstinence.”
Josepher notes that much of his own program’s funding comes through AIDS money under the Ryan White CARE Act or SAMSHA rather than NIH. “I think there is hope and we could be reaching and engaging a lot more people than we are. …we’re just locked into the way we think about treatment and recovery.”
PARTNERSHIP WITH PRIVATE INDUSTRY - A PATH TO SUCCESS OR SOMETHING ELSE?
In an attempt to stimulate a partnership of ideas and technologies between innovative small business and non-profit research institutions, the NIH offers its Small Business Technology Transfer (STTR) Grant program. By providing cash awards for cooperative R/R&D efforts with non-profit research institutions, the program assists the small business and research communities to commercialize innovative technologies.
The STTR program is structured in three phases, the first two of which are supported with STTR funds. The objective of Phase I is to establish the technical and scientific merit and feasibility of the proposed research and development efforts. The objective of Phase II is to continue the research or R&D efforts initiated in Phase I.
Bill Chin, MD, executive vice president of scientific and regulatory affairs for PhRMA in Washington, D.C., sees the recent development of public and private collaborations as a positive trend. “It will take more than one lab and one government agency,” said the former dean of research at Harvard. “We need to come together. Multiple brains together are better than one.”
Nonetheless, a great many people question private industry research quality and motives given a past history of questionable research and accusations of publishing bias. Many scientists are wary of substance abuse research funded by pharmaceutical companies or the alcohol industry, Humphreys for one. "I chose to not go that route,” he says about his research (he focuses on the prevention and treatment of addictive disorders, the formation of public policy and the extent to which subjects in medical research differ from patients seen in everyday clinical practice). “People of great integrity do get this funding,” he said. “But are the results affected? The question is for the public - do you want the people who evaluate care or those with an economic interest in the issue to do the research?”
The validity of privately funded research is "a major problem we’re trying to address,” Says Srijan Sen, MD, PhD, assistant professor of psychiatry, neuroscience and bioinformatics at the Molecular and Behavioral Neuroscience Institute of the University of Michigan, Ann Arbor. “It’s problematic when we are relying almost exclusively on drugs funded by pharmaceuticals companies.“
A major reason for skepticism is the growing practice of selectively publishing trial results that serve an agenda. Dr. Sen points to a study published in the New England Journal of Medicine which found that Pharma-funded research has a 97% "significant effect" on the outcomes of published studies, as compared to a 51% significant effect on studies funded by government or non-profits. “There’s a huge bias in what’s getting out,” Sens says. “Only positive results are published.”
Nearly 100 studies have drawn the same conclusion: publishing bias occurs far more often when studies are funded by industry versus non-industry.
Of course, even by these stats, not every industry-funded research is tainted. As ADIAL’s CEO Stilley notes: “We are highly regulated and it would be difficult to tamper with.”
Stilley points to AD04’s primary investigator, ADIAL’s chairman, Professor Bankole Johnson, MD, a neuroscientist and pioneer in the development of medications for the treatment of alcohol abuse. He was the 2001 recipient of the Dan Anderson Research Award for his “distinguished contribution as a researcher who has advanced the scientific knowledge of addiction recovery” along with many other awards, including Distinguished Senior Scholar of Distinction Award in 2002 from the National Medical Association. Johnson also was an inductee of the Texas Hall of Fame for contributions to science, mathematics, and technology. “He’s in there to help patients,” says Stilley.
For its part in seeking to limit industry influence, the Food and Drug Administration (FDA) requires registration and full financial disclosure by clinical investigators concerning their compensation sources and all financial interests.
Says PhRMA’s Dr. Chin: “We need to get together, hold hands and help each other in the near and distant future.”
No doubt true. Still, another important factor in drug research by industry is what Dr. Sen calls the phenomenon of funding "me-too" drugs, using Prozac as an example. “The most original drugs were in the 1940s to the 1960s. So many of the drugs today are the same chemical derivatives of old drugs. Eight-to-10 new SSRIs are just tweaks of Prozac,” he says. “They are no more effective but a lot more expensive."
Nor has the industry dived in to substance abuse relief where there is no clear path to high profits. One major example: not funding research vaccines that block the craving for heroin or other drugs because vaccines are seen as unprofitable for most drug abuse.
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Kathleen Phalen Tomaselli has written for the Washington Post, the LA Times, USA Today and American Medical News, among other publications. This is her first article for The Fix.