Insurers Question Studies of ADHD Drugs

WSJ Article Excerpts:

By ANNA WILDE MATHEWS
Staff Reporter of THE WALL STREET JOURNAL
August 24, 2005; Page A1

DOWNEY, Calif. – When Eli Lilly & Co. wanted to get the big California health-maintenance organization Kaiser Permanente to use its new antidepressant, it ran straight into Debbie Kubota.

As the cost of drugs in the U.S. approaches $250 billion a year, pharmaceutical companies are running up against a growing breed of detective trained to see through marketing spin. Working for insurers, state Medicaid programs and nonprofit bodies, these detectives cast a wary eye on published studies in medical journals, once considered an unimpeachable source. They search for subtle aspects of clinical-trial design that might show the drugs are not all they’re cracked up to be.

“You could be duped,” says Siri Childs, who oversees pharmacy policy for the Washington state Medicaid program. “We know now that just because it’s published in a medical journal, that doesn’t assure its quality.”

The Cochrane Collaboration, a nonprofit that analyzes the quality of studies and collects the ones it considers good into broader analyses, has a volunteer corps of about 7,500 reviewers, mostly doctors and academics. That’s up from about 2,800 five years ago. Another player is the Drug Effectiveness Review Project, an effort by an Oregon nonprofit. It issues reports summarizing all the studies in a particular treatment area and often criticizes individual studies for failings such as inadequate controls and high dropout rates.

Some journals are trying themselves to help readers discover marketing messages slipped in amid the scientific data. Last year BMJ, a British journal, published a piece called “Users’ guide to detecting misleading claims in clinical research reports,” which came with a picture of a reader dumping salt on a medical journal. One piece of advice: Beware when the authors break out one subgroup of patients and claim benefits from the treatment that weren’t evident in the whole group.

Dr. Kubota, a 26-year Kaiser veteran who holds a doctor of pharmacy degree from the University of Southern California, is based in the industrial city of Downey, southeast of Los Angeles, across the street from an abandoned movie set. Kaiser tries hard to keep her and her colleagues away from the influence of the companies whose products they evaluate. Before meeting with Dr. Kubota, a representative of a drug company must fill out a form indicating who will be coming, what they plan to discuss and why the information can’t be relayed in written form. No gift pens, mugs or other trinkets are allowed. Dr. Kubota’s business card doesn’t show her direct phone number.

When Dr. Kubota started her current job in 1997, she says she “would just read the abstract,” the summary at the beginning of a study. “I guess I was naive,” she says. “You kind of assume everything is there for you in the abstract.” Today, she quickly homes in on details that aren’t mentioned in the abstract and generates a 6-inch stack of papers studded with Post-it notes for each drug.

When she reviewed Adderall, a stimulant now marketed by Shire Pharmaceuticals Group PLC to treat attention deficit hyperactivity disorder, she noted that one of the major trials included only people who had responded well to Ritalin, another ADHD drug. She thought the move likely improved the results. Dr. Kubota recommended leaving Adderall off Kaiser’s formulary. The physician committees partially overruled her, putting Adderall on the Northern and Southern California formularies but only for patients who failed to respond to another stimulant. Adderall later was added to the preferred list as a first-line treatment after a once-daily formulation went on the market.

A spokesman for Shire, Matt Cabrey, said that the designers of the trial, which was conducted when Adderall belonged to another company, felt that for ethical reasons they should give the drug to people with a “reasonable anticipated reaction.” James Swanson, the lead author of the article that described the trial’s results, said the trial was designed to show whether Adderall works faster than Ritalin.

Are ADHD drugs safe? Report finds little proof

M. ALEXANDER OTTO;
The News Tribune
September 13th, 2005

At a time when millions of children and adults are taking drugs for Attention Deficit Hyperactivity Disorder, the most comprehensive scientific analysis of the drugs to date has found little evidence that they are safe, that one drug is more effective than another or that they help school performance.

The 27 drugs studied included Adderall, Concerta, Strattera, Ritalin, Focalin, Cylert, Provigil, and others that, in some households, are well-known for their sometimes calming affects.

The 731-page report was done by the Drug Effectiveness Review Project, based at Oregon State University. The group analyzed 2,287 studies – virtually every investigation ever done on ADHD drugs anywhere in the world – to reach its conclusions

They found:

• “No evidence on long-term safety of drugs used to treat ADHD in young children” or adolescents.

• “Good quality evidence … is lacking” that ADHD drugs improve “global academic performance, consequences of risky behaviors, social achievements” and other measures.

• Safety evidence is of “poor quality,” including research into the possibility that some ADHD drugs could stunt growth, one of the greatest concerns of parents.

• Evidence that ADHD drugs help adults “is not compelling,” nor is evidence that one drug “is more tolerable than another.”

• The way the drugs work is, in most cases, not well understood.

The findings do not mean ADHD drugs are unsafe or unhelpful, just that sound scientific proof is lacking.

The Pharmaceutical Research and Manufacturers of America, the Washington, D.C.-based drug industry lobby group, had no comment on the report, but its senior vice president, Ken Johnson, said the benefits of most drugs “clearly outweigh the risks.”

ADHD is suspected when people have a harder time than others their ages paying attention, sitting still or controlling impulses. To be diagnosed, those tendencies must interfere with work, school or other activities.

Nationally, about 4.4 million kids between 4 and 17 fit the bill. Of those, more than 2.5 million take ADHD drugs. Up to 8 percent of kids in Washington state have been diagnosed with the condition.

The Drug Effectiveness Review Project was formed in 2003 to give consumers and state insurance plans trustworthy information about pharmaceuticals.

Industry studies, which researchers have shown sometimes are rigged for favorable outcomes, don’t give the confidence “many of us would like to decide whether or not we should be using a given medication,” said the project’s deputy director, Mark Gibson.

Complicating efforts to get reliable information, the U.S. Food and Drug Administration doesn’t require companies to compare new drugs to ones on the market. Most times, firms instead compare their wares to sugar pills because it is easier to show benefit and get approved for sale.

The problems leave insurers and patients in the lurch when they need to know what drugs work best. That’s where the Drug Effectiveness Review Project comes in. Its physicians and pharmacists analyze virtually every study on a given class of pharmaceuticals to find the best drugs.

The American Association of Retired Persons and Consumers Union, the publisher of Consumer Reports, use the project’s findings to tell people what drugs give the most for the money. Fourteen states, including Washington, also use its services to decide what drugs to cover for beneficiaries. Those states are the project’s chief funders.

For ADHD, the project analyzed published studies as well as unpublished data from the six leading makers of ADHD drugs. The group rejected 2,107 investigations as unreliable, and reviewed the remaining 180 to find superior drugs.

Instead, it found that evidence to choose one drug over another for safety or effectiveness is “severely limited” by a lack of studies measuring “functional or long-term outcomes.”

The project could not find a “good quality” study that tested the drugs against each other. It also could not find comparative evidence to determine which ADHD drugs are less likely to cause tics, seizures and heart and liver problems.

That evidence is needed. Canadian authorities have recently warned against using Adderall Extended Release in patients with heart problems. Cylert and Strattera have been linked to liver damage, the report said.

Until better research is done, the findings mean that choosing the right ADHD drug is largely a matter of trial and error. They also suggest some people might do as well or better on cheap generic Ritalin, sold by its scientific name methylphenidate, instead of far more expensive, newer options such as Concerta and Adderall.

In fact, in the few instances where the Oregon group could draw conclusions, it found Concerta “did not show overall difference in outcomes” compared to generic Ritalin, and proof that Adderall is better “lacking.” What little evidence there is comparing another newer expensive drug, Strattera, to generic Ritalin “suggests a lack of difference in efficacy.”

Gibson cautioned that his project’s latest report is still open for public comment and possible fine-tuning. But the overall results did not surprise Libby Munn, a nurse practitioner at Greater Lakes Mental Healthcare in Lakewood.

“I’ve never been aware of any evidence of any one being better than another,” said Munn, who treats patients for ADHD and other conditions. “That’s true of antidepressants and antipsychotics, too. Once you compare meds for a given disorder, there are often no proven differences.”

Tacoma psychiatrist Dr. Fletcher Taylor, an expert in adult ADHD at Rainier Associates, works with drug companies to develop new products. He said he stands by the effectiveness and safety of the drugs.

Still, he said, Adderall and Concerta are largely equal in their effect, though some people do better on one than another. Their greatest advantage over generic Ritalin is that people take fewer pills during the day.

ADHD DRUG COSTS*

• Methylphenidate (generic Ritalin) $15.69

• Ritalin (brand name): $27.79

• Amphetamine/dextroamphetamine (generic Adderall): $47.09

• Adderall (brand name): $94.49

• Concerta: $103.99

• Strattera: $123.99

• Focalin: $25.99

*Comparisons based on the lowest dose for 30 days.

Source: Walgreens Pharmacy

FIND THE RIGHT DRUG

These Web sites offer help comparing drugs to find what works best:

• The American Association of Retired Persons lets you compare drugs at www.aarp.org/health/comparedrugs/

• Consumers Union, the publishers of Consumer Reports, gives tips on the best drug buys for safety and effect at www.crbestbuydrugs.org/

• The consumer-advocacy group Public Citizen has a solid record of spotting problem drugs, calling, for instance, for the removal of Vioxx in 2001, when few knew there were problems. The group is now worried about the cholesterol pill Crestor. Public Citizen’s drug information site is www.worstpills.org/

• The Oregon State University Drug Effectiveness Review Project is online at www.ohsu.edu/drugeffectiveness/

M. Alexander Otto: 253-597-8616 alex.otto@thenewstribune.com

New ADHD Drug to Fix Your Child

McNeil Consumer & Specialty Pharmaceuticals, a division of Johnson & Johnson (“J&J”), announced that an agreement with  Cephalon, Inc. to Co-Promote Modafinil for Attention-Deficit/Hyperactivity Disorder (Thursday September 1). McNeil currently manufactures and distributes Concerta for AD/HD.

Modafinil (coated tablet) is a form of Provigil which is used to alleviate excessive sleepiness  (narcolepsy) and other sleep disorders. Cephalaon and McNeil are awaiting U.S. Food and Drug Administration (FDA) approval for the treatment of attention- deficit/hyperactivity disorder (ADHD) in children and adolescents.

By combining sales forces totaling more than 700 sales reps between the two companies and by marketing heavily, the agreement may produce heightened sales figures for both companies in a competitive multi-billion dollar market. Cephalon will pay McNeil commission fees calculated as a percentage of annual net sales of Modafinil during the term of the agreement according to their press release.

Look for Shire Pharmaceuticals to market a new drug ostensibly in the same manner as J&J to compete.

In J&J’s press release they say that “Our company has extensive experience with ADHD and the pediatric medical community,” said Colin F. Watts, president, McNeil Consumer & Specialty Pharmaceuticals, a subsidiary of Johnson & Johnson. “We are excited about the prospect of collaborating with Cephalon on this new ADHD therapy.”

The most frequently reported adverse events in clinical trials with PROVIGIL were headache, nausea, nervousness, stuffy nose, diarrhea, back pain, anxiety, trouble sleeping, dizziness and upset stomach.

It has always been a concern of mine that ventures like these will reap a large profit without addressing cognitive, behavioral, and social needs of the end user. The public’s current perception is that using these medications will indeed ‘fix’ their broken child. Unfortunately, and according to the National Institutes of Health, more than medication is needed to address the full needs of AD/HD children. So, as long as pharmaceutical companies keep marketing in a manner which encourages the public’s ‘fix’ perception, we’ll continue to have kids who historically remove themselves from medication whenever they can (usually upon emancipation) and carry their AD/HD into adulthood with no compensatory skills.

ADHD ADD Drug Adderall XR Back on the Market in Canada

Bloomberg reports  Shire Says Canada Allows Sale of Adderall XR Again  after appealing Health Canada’s decision to pull Adderall XR from Canadian shelves.

h Canada’s decision was based on Adderall XR’s link to 20 deaths.

Bloomberg cites that “Adderall XR, used to treat attention deficit hyperactivity disorder or ADHD, will return Aug. 26, the Basingstoke, England- based company said today in an e-mailed statement. The medicine was taken from the market Feb. 9 at the request of Health Canada.

Shares of Shire fell 10 percent the day after the removal in Canada, which only accounted for $10 million of the product’s $606.7 million in 2004 sales. Adderall XR, which has about 25 percent of the hyperactivity market, is also facing patent challenges from companies including Barr Pharmaceuticals Inc. and Impax Laboratories Inc.”

Shire is the UK’s third largest pharmaceutical company.

Autism and Parents Education

LONDON, UK: The Daily Telegraph reports of a highly controversial study indicating that parents of autistic children tend to be more highly educated than parents of children with other mental problems. Researchers found that 46% of parents of autistic children achieved a General Certificate of Secondary Education (GCSE) compared to 35% parents of other children in the study. A GCSE is the name of a set of British examinations, usually taken by secondary school students.

The study, conducted by the Office for National Statistics, was an attempt to closely examine children with autism as well as to determine whether mental disorders were rising.

Researchers found that autistic children were also less likely to live in poor families. However, many autistic children live in families where neither parent worked. While only nine percent of parents with autistic children earned less than £200 per week, 20 percent of other children lived in homes with a weekly income of less than £200 per week.

Researchers suggested that the unusual combination of high educational status and low economic activity among parents of autistic children “reflects their heavy caring responsibilities.”

Seven percent of US children are suspected of having ADHD while the British study indicates on two per cent had Attention Deficit Hyperactivity Disorder (ADHD), and only one per cent had a less common disorder, such as autism. As is true in the US, boys were more likely to have a mental disorder than girls.

“The prevalence of mental disorders was also greater among children and young people in certain families, such as lone parent families (16 per cent) compared with two-parent families (eight per cent) and in step-families (14 per cent) compared with those with no stepchildren (nine per cent).

Dinah Morley, deputy director of Young Minds, the children’s mental health charity, said the figures were a wake-up call to the “tremendous cost” of divorce.

“We can’t turn the clock back to a time when all children stayed with their birth families,” she said. “But we can start to be more aware that these things that adults do impact very deeply on children. I think it is a wake-up call to adults to be more aware when they decide to divorce of the tremendous cost to the children. It is important for society to think how in the future it is going to support children better.”

However, statisticians emphasised that while there was a link between divorce and mental health problems in children, it was not clear whether the divorce followed the diagnosis of the mental problem or whether it may have triggered it in some way.

They added that mental health problems in children were also more common where the parent had no educational qualifications (17 per cent) compared with those who had a degree (four per cent) and where a parent was an unskilled manual worker (15 per cent) compared to a doctor or lawyer (four per cent).

One per cent of children aged 5-16 had autistic spectrum disorder.

The majority – 82 per cent – were boys. Almost all the children had a physical complaint as well (89 per cent compared with 54 per cent of other children).

Tim Loughton, the shadow Health Minister, said: “The Government urgently needs to make it easier to identify problems early on in schools and to provide appropriate treatment. That does not mean admission to adult wards or excessive reliance on the chemical cosh of drugs.”

(Source: Daily Telegraph, September 1, 2005)

Adult ADD: Many Children Maintain their Disorder into Adulthood

ADHD haunts children into adulthood, study shows

Psychological Association published research from Dr. Mariellen Fischer, a psychologist with the Medical College of Wisconsin. Her study was co-authored by Dr. Russell Barkley. The results of her 13 year study show that if AD/HD is left untreated in childhood, children will carry their disorder into adulthood.

For thirteen years they monitored 147 children with ADHD by age 7, comparing them with 76 neighbor children who didn’t have the disorder. About one third dropped out of high school. This seemed significantly high as none of the neighbor children dropped out. Leaving school is quite likely due to the public school system’s inability to accommodate the needs of ADHD students as well as ADHD student inability to learn coping skills which are seldom taught in school or at home.

Interesting data about adults with AD/HD in this study:

  • They are more likely than their peers to get fired
  • They are more likely to shun birth control and become parents by age 21
  • They are more likely to have higher credit card debt and fewer saving
  • They took medication for AD/HD as children, but few were being treated by their early 20s
  • They are more likely to start having sex a year earlier than classmates
  • 1 out of 3 had become parents by their early 20s vs. 1 in 25 of the classmates
  • They had less than half the savings of young adults they had grown up with and more debt

Dr. Fischer indicated that many children maintain their disorder into adulthood. The article is not clear whether this data was relevant to treated or untreated ADHD. However, clinical data suggests that perhaps 60% of ADHD children will carry their disorder into adulthood. This may be a conservative estimate.

While the data are compelling, the study is too small to conclude that ADHD alone causes these ill effects.

Genetics and ADHD ADD

Clearly, there is no current research (2005) that has determined that ADHD is genetic either partially or entirely. While empirical data suggest that a genetic link exists, research is still sparse as scientists primarily focus on childhood onset of the disorder with little research on adult AD/HD.

Andrea Chronis of the University of Maryland  has focused on AD/HD mothers and their performance as parents. In her study of 70 families with elementary-school-age children she found that:

  • Mothers of ADHD children are 24 times as likely as the average woman to have it
  • Fathers of ADHD children are 5 times higher than average to have it
  • The mothers often weren’t very involved with their children
  • The mothers had few skills to cope with their children
  • The mothers didn’t give praise or show affection regularly
  • Discipline was inconsistent
  • Most of their children also had ADHD

While Chronis’ research does not prove a genetic link, it offers strong support for the theory. And while poor parenting may exacerbate ADHD symptoms, it does not cause ADHD. Thus, the aforementioned poor parenting skills would likely contribute to worsening their childrens’ symptoms. This would lead one to think that parenting skills/counseling should be a primary consideration for families with ADHD.

Girls With ADHD and ADD Are Often Overlooked

Girls With ADHD Are Often Overlooked

HealthNewsDigest.com – August 29, 2005 (HealthNewsDigest.com) reports that ADHD likely affects 3% to 7% of the entire child population in the US. However, girls are frequently overlooked because they often do not display hyperactive symptoms.

When teaching at the elementary level, I found this particularly true. Girls with ADHD often were simply daydreamers with poor time management skills. While some did display the outward social and behavioral problems that their male peers did, it was not very frequent.

HealthNewsDigest.com is published by the American Psychological Association. I’ve cited bits of this report and am alarmed by its look and feel. It reads like an endorsement and advertisement for Adderall XR.

Their report, edited down:

The federal Food and Drug Administrations (FDA) recent nod to ADDERALL XR for the treatment of attention deficit hyperactivity disorder (ADHD) in adolescents aged 13 to 17 spotlights an underidentified and under treated population with this disorder, experts tell Health NewsDigest.com.

If left untreated, the symptoms of ADHD can have a profound effect on a child’s life, both inside and outside of a classroom setting.

For Janice Lowder, a quiet, well-behaved child, learning was always stressful.

“My husband and I hired a one-on-one tutor to help Janice with her studies. We also tried to help her, and all dreaded the nightly battle of completing a homework assignment. Janice would get so frustrated with her homework and the fact that she didn’t ‘get it,’ that she would cry,” said her mother Beth Lowder.

“By the time Janice reached the seventh grade, a nurse at her school suggested we talk to a doctor. Janice was diagnosed with ADHD and was started on treatment,” Beth explained.

“I knew my daughter just needed the right help,” said Beth.

By the tenth grade, Janice had improved from a C to a B student but homework was still challenging. In addition, she had low self-esteem and was embarrassed to take her medication at school. Her psychiatrist prescribed Adderall XR®, an extended-release formulation that enabled Janice to take her medication once a day at home.

With continued tutoring and medication, her grades improved.

“She came home from school one day and said, ‘Mom, I’m smart,’” said her mother.

A recent study presented at the American Psychiatric Association annual meeting showed that girls with ADHD demonstrated significant improvement in both behavior and attention with Adderall XR.

“The study suggests that girls with ADHD can benefit from Adderall XR and that this treatment will help them control symptoms all day while they are in the classroom, during after-school activities or doing homework with relatively few side effects,” said Joseph Biederman, M.D., professor of psychiatry, Harvard Medical School and Chief of Pediatric Psychopharmacology at Massachusetts General Hospital. “While ADHD in girls is becoming more recognizable it is still often overlooked, and there is a need for safe and effective treatments that will allow girls to interact more effectively with other children and adults, to concentrate in school and to focus on finishing tasks.”

I’d expect to find a more diluted version in Parents Magazine or Family Journal as an outright advertisement. Makes one wonder who wrote this? Shire Pharmaceuticals?

IEP: An ADHD ADD Student Right

To IEP or not to IEP that’s the $100,000 question!

MICHAEL BARBER of the Bradenton Herald reports that:

 The Manatee County school district has spent more than $100,000 in legal fees battling an attempt to get an 11-year-old boy with attention deficit disorder a special education plan, according to documents The Herald reviewed.”

Since the AD/HD boy has performed well academically and on the Florida Comprehensive Assessment Test, the school doesn’t believe it’s responsible to provide a special education Individualized Education Plan (IEP).

School officials argue that accommodating this student could set a costly precedent for the district and state by allowing thousands of other ADHD students to apply for special education plans.

Final arguments in the federal case were heard in Tampa on Thursday. U.S. District Judge James Whittemore is expected to render a decision in the next couple of weeks.

While I agree that this could precipitate a flood of AD/HD requests for accommodation, what’s more important here, students’ educations and well beings or money?

Every student has a right to an IEP.

It simply defines what goals and objectives will be used over the student’s academic year to achieve success. If some accommodations like computer software, lengthened test time, etc. need to be implemented, then do it. It is mandated and paid for by the federal government under IDEA (Individuals with Disabilities Education Act). It does require extra effort and perhaps even extra staff to write and implement the IEP.

“On Thursday, Superintendent Roger Dearing told The Herald the district had spent an estimated $50,000 on the case.

…Although exact legal fees the school district paid to the various firms were not available Friday, district records indicate the total figure spent on the case exceeded $100,000.

When asked whether he thought the $100,000-plus legal tab was worth it, Dearing was emphatic.

“Would you spend $100,000 to save $10 million?” Dearing asked.

Dearing said that there are more than 2,000 students in Manatee County schools who are ADHD and that special education plans can cost $5,000 or more. If all of those ADHD students applied for special education plans, the cost could be as much as $10 million per year.”

In order to save money, the school system is arguing that AD/HD is not covered by the IDEA.

School board members Larry Simmons and Harry Kinnan both said they did not like having to spend district money on costly court cases, but in this instance they thought it was the right thing to do.

“I think it’s an important enough case that we have to spend what it takes,” Simmons said. “It’s not about this particular young man or his mother. It’s about a potentially serious financial impact to the school district.”

Kinnan agreed.

“I think it’s regrettable the money can’t be marked for other things, but we’ve decided as a school district that it’s important to stop a precedent from being established,” Kinnan said.

“You have to weigh the implications for the school system if you don’t fight this case.”

Who is right? and who is wrong? seem to be moot questions. The question is, what is the best education for this child and what would a special education IEP provide that? If that answer is yes, then do the right thing. We’ll see what the courts say.

9/8/2005 Adults with Attention Deficit Hyperactivity Disorder Do Well on Deadline and Love a Challenge?

From the Kansas City Star by DIANE STAFFORD:

ADHD SUFFERERS FIND THEIR NICHE: Adults with Attention Deficit Hyperactivity Disorder Do Well on Deadline and Love a Challenge?

Can you say clueless? Stafford interviews Dr. William Dodson, MD who spoke to about 50 Hallmark Cards employees. His recommendation? If you want an employee who performs best on deadline, hire someone who has trouble staying on task. Dodson apparently specializes in treating with AD/HD. He said that adults with the neuropsychiatric condition generally respond well to urgency and fast pace. This seems true, meeting deadlines? That’s one of the greatest problems for adult AD/HD people.

“Workers with ADD need to be challenged or feel competitive,’’ Dodson generalized. “They like the new, the novel, the fleeting. They need ADD-friendly jobs – not accounting.’’

Sure they do. They are great in marketing. But don’t rely on them to get a job done on time. I’ve worked with many AD/HD adults. They’ll accept 20 jobs and finish none of them. Dodson truly seems clueless here.

Stafford also cites Blythe Gross, who has a doctoral degree in organizational psychology, also specializes in ADD treatment. After working with or interviewing hundreds of adult ADD patients, Gross wrote Making ADD Work: On-the-Job Strategies for Coping with Attention Deficit Disorder. Gross has been in the trenches with hundreds of AD/HD adults. She’s much more realistic in her perspective. She indicates that adult AD/HD “symptoms can range from an inability to get started on a task, to an inability to follow through on a task, to perfectionism that makes a project drag on forever because it’s never good enough.” This statement is the antithesis of Dodson’s.

I’d go with Gross and recommend her book, Making ADD Work: On-the-Job Strategies for Coping with Attention Deficit Disorder. With so many ‘experts’ on this subject, someone has to cry ‘baloney’ when nonsense like Dodson’s is put to press.