26 March 2007

Leanne Jardine

Prescription Drug Program Manager

Department of Health & Wellness

Carleton Place

PO Box 5100

Fredericton, New Brunswick

E3B 5G8

Dear Ms. Jardine:

Re: Treatment of ADD/ADHD in New Brunswick
I am writing to you on behalf of the Centre for ADD/ADHD Advocacy Canada (CADDAC), of which I am a Director. CADDAC is a national Canadian alliance of organizations and individuals. CADDAC is striving to enable all Canadians affected by ADHD through advocacy and education.
CADDACs goals include:

• creating awareness within the health care system, the education system, amongst regulators, employers and the public and,

• networking with professional organizations and other stakeholders to maximize knowledge and understanding of ADHD.

It is with these goals in mind that I am writing to you today.

ISSUE TO BE ADDRESSED
CADDAC believes access to appropriate therapeutic options, as outlined in the Canadian ADHD Practice Guidelines (www.caddra.ca/english/pdfs/Medication_17.pdf) are key to success for individuals with ADHD as well as their caregivers and families. This is not the only important aspect of managing ADHD but it is the only one within your control. Therefore, I will address only this issue in this submission to you.
The treatment of ADD/ADHD requires a comprehensive approach that includes educational accommodations and other specialized training. However, in order to achieve the goals of educational accommodations and other measures, the subject needs to be able to pay attention, not be distracted and not engage in impulsive behaviours. Medication is used as a critical supportive measure.

Improved awareness of appropriate drug treatment for ADHD is one step towards improved outcome. A better understanding of ADHD helps healthcare professionals such as yourself, recognize and identify individuals that need your support. It is important for you to decrease the stigmas associated with ADHD. Much like depression in the last century, lack of awareness of the fundamental symptoms of ADHD results in no diagnosis, misdiagnosis, no treatment or sub-optimal treatment.

At this point in time, the New Brunswick Prescription Drug Program is contributing to the no treatment or sub-optimal treatment situation in New Brunswick today and you can do something to address this right now by including first line agents in the New Brunswick Prescription Drug Program Formulary.

Attached, please find a position paper from CADDAC that outlines our concerns.

CONCLUSIONS AND RECOMMENDATIONS
CADDAC’s position is that children in New Brunswick, regardless of their parent’s income, should have equality of access to first line agents in the treatment of ADHD. In order for children in New Brunswick to get access to the educational accommodations your government has implemented and will be implementing in the future, they also need access to the best drug treatment Canada has to offer. You can rectify this situation by moving first line agents to general listing.
Sincerely,

Dianne Azzarello, BSc. Phm.
cc: Heidi Bernhardt, CADDAC

Hon. Shawn Graham

Hon. Kelly Lamrock

Hon. Michael Murphy

Hon Carmel Robichaud

Bernard Richard

ISSUE TO BE ADDRESSED
CADDAC believes access to appropriate therapeutic options, as outlined in the Canadian ADHD Practice Guidelines (www.caddra.ca/english/pdfs/Medication_17.pdf) are key to success for individuals with ADHD as well as their caregivers and families. This is not the only important aspect of managing ADHD but it is the only one within your control. Therefore, I will address only this issue in this submission to you.
The treatment of ADD/ADHD requires a comprehensive approach that includes educational accommodations and other specialized training. However, in order to achieve the goals of educational accommodations and other measures, the subject needs to be able to pay attention, not be distracted and not engage in impulsive activities. Medication is used as a critical supportive measure.

Improved awareness of appropriate drug treatment for ADHD is one step towards improved outcome. A better understanding of ADHD helps healthcare professionals such as yourself, recognize and identify individuals that need your support. It is important for you to decrease the stigmas associated with ADHD. Much like depression in the last century, lack of awareness of the fundamental symptoms of ADHD results in no diagnosis, misdiagnosis, no treatment or sub-optimal treatment.

At this point in time, the New Brunswick Prescription Drug Program Formulary is contributing to the no treatment or sub-optimal treatment situation in New Brunswick today and you can do something to address this right now by including first line agents in the New Brunswick Prescription Drug Program Formulary drug formulary.

BACKGROUND
Symptoms of ADHD
In plain English, the symptoms listed in the DSM-IV for ADHD include the following:

• Careless mistakes
• Difficulty sustaining attention
• Easily distracted
• Difficulty organizing
• Fails to finish tasks (shifting activities)
• Seems not to listen
• Avoids tasks requiring sustained attention
• Loses things
• Forgetful

This is not the profile of a patient who can be successful taking drug therapy three times a day. Factor in that we are talking about children as young as 6 years old and the concept of treating such a person with multiple-daily doses seems incredible.

Since ADHD is a genetic¹ neurological disorder, chances are at least one of the parents has the same symptoms. It is unreasonable to expect parents with ADHD themselves to successfully supervise and/or organize the administration of three times a day medication to their ADHD child.
Canadian ADHD Practice (CAP) Guidelines (www.caddra.ca/english/pdfs/Medication_17.pdf)
The following paragraphs are excerpted from the current Canadian ADHD Practice (CAP) Guidelines.

“The mainstay of medical management has been psycho stimulant medical therapies. These drugs have been around for 50 years with thousands of research papers on their safety and efficacy. However, in the last five years, the development of once-daily delivery systems has significantly improved the utility of these formulations by preventing peak and valley effects, the potential for substance abuse and the privacy concerns commonly associated with their shorter-acting counterparts… Even with medication alone, we are now able to improve the main symptoms of ADHD in a very short period of time. There is a real possibility that we can move many patients even further to symptom remission. Research is improving our knowledge about response rates and decreasing side effects.
The major disadvantage of long-acting medications is their cost and accessibility. Government formularies do not cover these medications, although they are almost completely covered by the majority of private insurance plans. This has effectively created a two-tiered medical system where the first question you may have to ask is, "Do you have insurance?" Short- or moderately-acting medications are still very successful but they require more stringent monitoring, multiple dosages per day, and the cooperation of the school. They also stigmatize the child in school, particularly among their peers. This stigmatization seriously affects the child’s compliance in taking the medication and his/her self-esteem.”
The CAP Guidelines recommend once-daily delivery systems as the ONLY first line agents (See Attachment 1 and Table 1 below). The reasons for this are numerous and they are summarized here from the perspective of the patient, the caregiver and the family members. The following table lists the agents included in the CAP Guidelines.

Table 1: Medications for ADHD
First Line Agents*	Second Line or Adjunctive Agents	Off Label Agents
Adderall XR, Concerta, Strattera	Dexedrine, Dexedrine Spansules, Generic MPH, Ritalin, Ritalin SR	Apo-imipramine, Wellbutrin SR

*Please note that Biphentin was approved after the guidelines were finalized but it should be included as another first line agent.
Current New Brunswick Prescription Drug Program Formulary Coverage of First Line Agents
Tables 2 and 3 below list the status of the four first line agents in the New Brunswick Prescription Drug Program formulary. As you can see, the New Brunswick Prescription Drug Program Formulary offers zero coverage for first line agents. Only second line or adjunctive therapy is covered. It is difficult to understand how adjunctive therapy can be effective when the primary treatment is not covered.

Table 2: New Brunswick Prescription Drug Program Formulary coverage for first line agents
Adderall XR	Not mentioned in the formulary at all – No benefit
Biphentin	Not mentioned in the formulary at all – No benefit
Concerta	Not mentioned in the formulary at all – No benefit
Strattera	Not mentioned in the formulary at all – No benefit

Table 3: New Brunswick Prescription Drug Program Formulary coverage of medications for ADHD
Product Covered	Position in the CAP Guidelines
dextroamphetamine	Second line or adjunctive
Generic methylphenidate	Second line or adjunctive
Ritalin	Second line or adjunctive
Generic methylphenidate SR	Second line or adjunctive
Ritalin SR	Second line or adjunctive

Second line agents (covered on the Formulary) require three times daily dosing because of their short half-lives and consequent short duration of action. For example, immediate release methylphenidate has a duration of action of about 3 to 5 hours. This means, to cover a child in grade 8 who is doing about 1 hour of homework each night and participating in after school programs, the child must take a dose before school, a dose at lunch and a dose after school. This scenario poses several problems detailed in the following sections.
DURATION OF ACTION

1. Peaks and valleys

Remember the symptoms listed above. By their pharmacokinetic nature, blood levels of short acting ADHD medications move in and out of the therapeutic range several times a day. Imagine a roller coaster ride of emotions, three times a day, from a child’s perspective. Imagine going on this ride while you are in a classroom with 29 other students and one teacher. Imagine that you are expected to sit quietly in your seat, not speak out of turn and focus all your attention on one person who may be talking about something you have no understanding of. I think you can see, from a child’s perspective, this is just not acceptable. You can prevent this roller coaster ride by covering first line, once daily ADHD medications as general listings.

1. Periods of the day with no coverage, also known as “therapeutic gap”.

Essentially the medication is wearing off at critical times of the day.

• End of the morning classes – results in missed educational opportunities and potential for disruptive behaviour affecting other students learning.

• Lunch period (often unsupervised) – results in social and behaviour problems leading to unnecessary discipline issues and or stigmatization.

• End of the afternoon classes - results in missed educational opportunities and potential for disruptive behaviour affecting other students learning. In addition, this is the time when children are expected to identify their homework for the night and gather together all needed materials, a challenge at the best of times and impossible without support (review the symptoms above).

• Transportation home (either unsupervised or during bus time) - results in social and behaviour problems leading to unnecessary discipline issues and or stigmatization.

This is like asking a child with vision problems to do their school work without their glasses or asking a child with hearing problems to listen to the teacher without their hearing aid or asking a child with diabetes to do anything at all without their insulin.

What does this mean to schools? - wasted resources, wasted time, poor educational performance, suspensions, expelling children, drop-outs etc.
What does this mean to caregivers and families? - missed days from work and school, relationship problems, low self esteem, substance abuse, legal difficulties etc.
What does it mean to children with ADHD? Failure
CADDAC believes the New Brunswick government has a responsibility to these children to ensure their success at school and to prepare them to enter the workforce as productive taxpayers.
What can you do to help this situation? Cover first line, once daily medications as general listings available to all.

1. Potential for missed doses

In a three times a day scenario of dosing, children must depend on multiple care givers and themselves to get access to their medication. It is not unexpected that some of the morning and after school doses get missed. You can call this what you want, non-compliance or a medication error, it is completely preventable. If first line, once daily medications and included in the formulary as general listings, the potential for missed doses can be significantly reduced.

Table 4: Dosing schedule and administration mechanism for immediate release products covered by the New Brunswick Prescription Drug Program Formulary
Morning dose	Usually a parent. Usually not a problem.
Lunch dose	Could be anyone - teacher, secretary, principal, volunteer or paid assistant. Possibly a different person every day. In some cases a parent has to go to the school to dose their child. No storage requirements. No record keeping requirements. At the discretion of the school board and/or school administration. No accountability for stability of medication, storage, diversion etc.
After school dose	Various possibilities – day care worker, parent, sibling, child him/herself. Not an ideal situation. SR form unlikely to carry the child through to the end of the school day and certainly will provide zero coverage for after school activities

This statement is from a 13 year old boy who forgot to take his medication, when he realized what had happened. “That’s why I was so jumpy today. I had to keep getting up out of my seat and going over to x’s desk. Mr. P kept glaring at me.” The missed dose stopped the boy from doing his work, stopped his friend from doing his work and took the teacher’s attention away from teaching and onto the boy. What is the cost of this activity? (See below Cost of missing an afternoon of school) .

1. Potential for abuse

Immediate release dextroamphetimine and immediate release methylphenidate have high potential for abuse. First line agents such as Adderall^® XR, Concerta^® and Strattera^® have very low potential for abuse. This is related either to the drug substance itself (e.g., Strattera) or the formulation (e.g., Concerta). Strattera cannot be used to induce a “high” and it is virtually impossible to extract the methylphenidate in Concerta for the purposes of abuse. Therefore, given the patient population to be treated, children and adolescents, CADDAC requests you cover first line agents not subject to abuse in the general listing of drug benefits.

1. Potential for diversion

Second line, short-acting agents are regulated as controlled drugs by Health Canada. As you know, there are strict controls on both the prescriber and the pharmacist in terms of record keeping, storage and distribution of these medications. However, the New Brunswick Prescription Drug Program expects / allows non-licensed dealers (schools and daycare centres) to warehouse and distribute these medications. Is this not in contravention of the Food and Drugs Act and Regulations as well as the Controlled Drugs and Substances Act? In addition, the New Brunswick Prescription Drug Program expects non-healthcare professionals to dose these medications. Is this not in contravention of pharmacy acts? By putting, high street value drugs with abuse potential in the hands of non-licensed school and day care staff, you are inviting these drugs to be diverted for financial or other personal gain. This situation is unacceptable to CADDAC and once again preventable. You should ensure that first line, once daily ADHD medications are the preferred treatment for school aged children and adolescents. In this way, parents can control the administration of these medications.

1. Stigmatization

Children with ADHD have a tough enough time at school as it is. The symptoms of their condition - inattention, distractibility, impulsivity and learning difficulties – invite ridicule on a daily basis. Sometimes even the teacher is the perpetrator of this ridicule. The New Brunswick Prescription Drug Program further stigmatizes these children by forcing them to access healthcare, i.e., drug treatment, in front of their peers. This leads to further embarrassment and loss of self esteem. Stigmatization leads to non-compliance with and even discontinuation of the drug treatment. You can do your part in supporting these children by covering first line, once daily ADHD medications as a general listing.
LONG TERM CONSEQUENCES OF NON-COMPLIANCE
In the discussion above, CADDAC has shown that use of second line, short-acting medications for the treatment of ADHD set up a student for failure because of the pharmacokinetic profile of these drugs. Essentially, second line agents define non-compliance (peaks and valleys, therapeutic gap) or lead to non-compliance (missed doses, abuse, diversion, stigmatization and discontinuation). In this case, non-compliance is equivalent to no treatment.

With hypertension, sometimes referred to as the silent killer, the consequences of non-compliance are not observed for years, if not decades. The same goes for conditions like osteoporosis and hyperlipidemia where fractures, cardiac events and deaths are long term outcomes. CADDAC believes ADHD is in a similar category but for different reasons. The long-term effects of untreated ADHD have also been identified by several researchers.

Wilens² listed academic limitations, relationship problems, low self esteem, injuries, smoking / substance abuse, motor vehicle accidents, legal difficulties and occupational problems as long term consequences.
Barkley³ identified childhood academic impairments such as poor school performance (> 90% of ADHD students), low academic achievement (10-15% deficit), increased parent-child conflict and stress and peer relationship problems (50-70% of children with ADHD). He has also reported antisocial activities in teenagers such as theft, lies, truancy, breaking and entering, property destruction, cruelty to people / animals, fighting, setting fires and carrying weapons. In terms of educational outcomes, Barkley reported that more ADHD students are placed in special education, more are suspended, have a greater expulsion rate, higher drop out rate, lower class ranking, lower GPA and fewer attend post-secondary education and less graduate from post-secondary education.
Barkley also reported that ADHD teens start sexual activity earlier, have more sexual partners, spend less time with each partner, are less likely to use contraception (they would need to be organized), have a greater risk of teen pregnancy / STDs and have a greater chance of not having custody of their children than teens who do not have ADHD.

Adults with ADHD enter the workforce at an unskilled or semi-skilled level. They are more likely to be fired, change jobs more often and have lower work performance ratings.

Biederman studied the impact of pharmacotherapy for ADHD on the risk of substance abuse⁴. He concluded the following:

• Unmedicated ADHD youths in mid-adolescence were at highest risk for substance use disorder.
• Medicated AHDH youths in mid-adolescence were at lower risk for substance use disorder compared with unmedicated ADHD youths.
• Medicated status was found to be protective against substance use disorder in ADHD youths in mid-adolescence.
• Pharmacotherapy for ADHD reduces the risk of substance use disorder in ADHD youths.

In fact a meta-analysis⁵ of 1195 young people concluded that drug therapy for ADHD resulted in half the risk of developing substance abuse.
COST OF FIRST LINE, ONCE DAILY ADHD DRUG TREATMENT VS COST OF ADHD
Cost of first line therapy
The Canadian guidelines summarize drug costs. Please refer to Attachment 2.

Cost of missing an afternoon of school
If we assume the noon dose of a second line agent is missed, this is equivalent to missing an afternoon of school. At best the child will be distracted and inattentive. Next worst possibility is the child could spend the afternoon in the principal’s office. At worst, the child would also lose the next day or two due to suspension. What is the value of an afternoon of school?

Using Ontario as an example, if we assume the Ministry of Education spends $17.5 billion per year on education (http://www.edu.gov.on.ca/eng/about/) and there are 1.9 million students, then the cost of one year of education for one student is about $9,200. If we assume there are 180 teaching days in a year, the cost for one day is about $51.00 per student per day. Therefore, an afternoon of missed school costs about $25.50.
A 60 kg, grade 8 student, treated with first line, once daily medication would cost between $3.20 and $8.76 per day, significantly less than the cost of the missed afternoon at school. CADDAC believes this would be a good investment in education.

Another way to look at this would be to look at students who are taking second line therapy covered by the formulary. In the best case scenario, we would assume both the morning and noon doses are taken. However, the therapeutic gap results in at least 2 “missed” hours of school per day for the entire school year. The cost of treating that student with first line, once daily medication would be between $576 and $1,577 on school days. The cost of the missing 2 hours per day would be $2,825 per school year per child. In this model, treating school aged children with first-line, once daily medication would actually save the government money overall.

These are simple examples, but they illustrate the cost of first line drug therapy versus the cost of education and demonstrate the value of first line therapy to the Ministry of Education. This should be taken into account when considering whether first line treatment should be covered. CADDAC believes it should.

Cost analysis of various therapies
Marchetti et al⁶ looked at the costs for treatment and management of school-age children with ADHD taking either a second line agent or two of the first line agents listed in the guidelines. Other products were evaluated in this study but they are not available in Canada and are not discussed here. Products in this study that are approved and marketed in Canada are listed in the table below. The total annual, per-patient expected cost of the various agents is also included in the table. The cost of the treatment the formulary pays for was higher than the cost of Concerta because the authors assigned a cost to the dispensing and administration of noon doses to children at school. For your information, the study was not sponsored by the makers of Concerta but by one of the manufacturers of a product not approved in Canada (Metadate CD). In addition, Thomas Einarson (University of Toronto, Faculty of Pharmacy) was one of the authors.
Another point made by these authors was that the actual cost of generic methylphenidate must be adjusted for non-compliance and consequent efficacy reduction of 25% making the true cost of generic immediate release methylphenidate even higher.

Table 5: Cost of treatment (Marchetti et al)
Treatment	Total expected cost
Concerta	$1631
Methylphenidate immediate release	$1845
Ritalin	$2080

Income losses to ADHD sufferers
A different look at cost of treatment assessed the loss of income associated with ADHD. Harvard University researchers interviewed 500 adults with ADHD and 501 adults in the general population matched for age and gender.⁷ From this research, they estimated that yearly household income losses to ADHD sufferers were in the range of $77 billion in the US. Matched for education, those with ADHD earned about $10,791 less per year for high school graduates and $4,334 less per year for college graduates. This translates directly into reduced tax revenue.
CONCLUSIONS AND RECOMMENDATIONS
CADDAC’s position is that children in New Brunswick should have equality of access to first line agents in the treatment of ADHD. In order for all children in New Brunswick to get the most benefit from educational accommodations, they also need access to the best drug treatment Canada has to offer. You can rectify this situation by moving first line agents to general listing.
Cost of ADHD medication treatment