A Fine Welcome Home

I return from vacation to find a brand new blog focused on my area of interest, sporting a link to AlignMap to boot.

Such a deal.

If I’m reading things correctly, Medication Noncompliance is just over a week old with five published posts, all of which are interesting, clearly written, and infused with intensity.

I’m too cynical to make predictions about the quality of my own future posts let alone those produced by someone else, but Medication Noncompliance is off to a good start and is certainly worth checking out, especially for those interested in issues associated with adherence to treatment.

• The Blog, The Resources, & The Rest
• The Blog Is Back - Posting On AlignMap Resumes
• The Times Makes Medication Noncompliance Official
• AlignMap Blog Hiatus: Summer 2007
• Noncompliance With Breast Cancer Medication

Leonard Cohen and Depression

Leonard Cohen’s music¹ has long been associated with depression, as noted in this introductory paragraph from an article in The Observer:

His depression,² in fact, seems to have been a significant factor in his life until it lifted in the 1990s. While Cohen has taken antidepressants, they were not the key to the dissipation of his despondency.

In this intervie,³ he discusses, with his characteristic candor and dark humor, his course of treatment and his decision to unilaterally discontinue these medications:

Commentary

Other than being the most recent addition to the AlignMap blog’s celebrity series,⁴ the story in this case is all too typical: Doctor prescribes antidepressants, Patient takes antidepressants, Antidepressants don’t help and also cause side-effects, Patient, without consulting doctor, stops taking antidepressants.

Footnotes

1. Leonard Cohen is one of my favorite artists and I write about him quite often in my personal blog, Heck Of A Guy. For my non-medical Leonard Cohen posts, see The Leonard Cohen Posts at Heck Of A Guy [back]
2. Cohen’s commentary on depression in general follows: “The term clinical depression finds its way into too many conversations these days. One has a sense that a catastrophe has occurred in the psychic landscape.” [back]
3. Mireille Silcott, A Happy Man, Saturday Night, Canada September 15, 2001, found at http://www.webheights.net/10newsongs/press/satnite.htm [back]
4. See also:
   ~Paris Hilton & Patient Noncompliance~
   ~Letterman, Pills, & Compliance Enhancement~ [back]

• SSRIs Vs Older Antidepressants: Effect On Compliance
• Paris Hilton and Patient Noncompliance
• Noncompliance and A Decision Not To Follow A Treatment Recommendation Are Not Identical
• Noncompliance Basics
• Noncompliance Costs

Underdosing, Overdosing, and Pill Splitting

Source

Ain’t Misbehavin’
Missing doses and other medication meddling are often no accident. A new study of patient compliance uncovers methods to the madness
Bill Chekan. Pharmaceutical Executive Feb 1, 2007

Primary Premise

While most compliance enhancement interventions have addressed unintentional noncompliance, a new study examines non-adherence that is purposeful and results from a decision the patient has reached through a rational process.

It should be noted that this article, Ain’t Misbehavin’ is not the original report from the study but a commentary about the study,

Study Parameters

The study was an online survey,¹ conducted in 2006 by Harris Interactive for Capsugel, a supplier of capsules for pharmaceutical and nutritional applications. The 1,012 US participants were a representative sample who take at least one pill at least once a day for at least one chronic condition.

“Chronic conditions” included a wide range of disorders, from relatively low severity (e.g., constipation) to life-threatening (e.g., cancer). Most common were “high cholesterol, allergies, cardiovascular concerns, arthritis, gastrointestinal issues, and psychological complaints.”

Results

43 percent of those surveyed reported being intentionally noncompliant at least once in the preceding 3 months.

Interpretations and Recommendations

The author of the article comments that the participants in the study, the criterion for which was taking at least one pill at least once a day for at least one chronic condition, “represent some of pharma’s most highly motivated consumers.”

The author also concludes that “the survey suggests that intentional noncompliance is generally driven by two main needs: to save money or to limit side effects.”

Interspersed throughout the article are examples of possible solutions to the problems raised. For example,

Dose Splitting

Much of the discussion is given over to dose splitting.

“Double-dosage splitters,” are those patients who obtain a prescription for twice the required dosage and then divide the pills in half such each fragment is equivalent to the prescribed amount. Those individuals save money since the medications are retailed at a flat rate per pill rather than per mg dosage and since half the co-pays are eliminated. The article makes a specific note that “most people were informed of this money-saving method by their doctors. And this group scores average or better on income and insurance coverage—these folks are less likely to need to save on meds and yet more likely to do so.”

“Single-dose splitters,” on the other hand, are those who intentionally decrease their dosage by dividing the prescribed dose and then taking that fraction of a dose. Single-dosage splitters are said to be “at the other end of the economic spectrum—poorer and with less access to insurance or drug coverage” and

The article continues,

Mention is also made that “the form of the medication (tablet, capsule, or softgel) appeared to have no influence on noncompliant behaviors. The only exception, understandably, was that double-dose splitting of pills was done exclusively with tablets, as capsules cannot be split.”

Commentary

I selected this article because (1) it specifically addresses intentional noncompliance which, as the author maintains, is addressed in the literature much less often than unintentional noncompliance and (2) it approaches the problem of noncompliance from pharma’s point of view, which I believe provides clinicians like myself a useful perspective on noncompliance as well as insight into the pharmaceutical industry’s thinking.

This shift from my typical perspective may have something to do with my discomfort with the article’s style and organization. The article, as one might expect, is less rigidly organized than a scientific paper. Data-based findings, subjective interpretations of those findings, and recommendations are blended in the same paragraph and, sometimes, the same sentence. Without access to the original study, I found it difficult at times to discern objective findings from the author’s deductions and inferences from that data.

I’m unclear, for example, why “participants [who] were a representative sample who take at least one pill at least once a day for at least one chronic condition” would be said to “represent some of pharma’s most highly motivated consumers,” especially given that studies have repeatedly shown that patients with chronic disorders to be among those most likely to be noncompliant.

Similarly, I was surprised to find the judgment that “the good news is that in general, people who had very serious medical conditions were less likely to be noncompliant,” was immediately followed by “the highest rates of nonadherence were reported by folks with depression or another psychological condition.” If a disorder such as depression, which can be completely debilitating and which carries a relatively high mortality rate isn’t considered a “very serious medical condition,” more information is necessary to support that contention.

When the original data is not accessible, as was the case in this situation,² it becomes the author’s responsibility to provide sufficient data to support conclusions made and to provide information from the study that would weigh against such conclusions. It was useful, for example, to know that the sensitivity level of the study for noncompliance was defined as one or more episodes of intentional noncompliance in the past three months, but given that some of the types of noncompliance discussed (e.g., pill splitting) would seem to occur almost every day, a further breakdown of the frequency of noncompliance is called for.

Nor does it seem likely that a doctor who suggests to a patient that he cut a 200 mg tablet in half to generate the prescribed 100 mg dose, would then label it “noncompliance” when the patient does exactly that. I suggest that would be considered “noncompliance” only from the perspective of the pharmaceutical industry. ³

Were there a Reader Reaction Scale that ranged from “High Approval” to “Utter Disgust,” I would predict that clinicians and health plan administrators would be on the “Approval” pole while pharma representatives would land on the “Disgust” end after reading this paragraph from the article:

The article then goes on

The implication, as I read this paragraph, is that pill splitting is potentially dangerous and steps (e.g., packaging changes) should be taken to stop it.

I would hold that if the central concern is how to address the “drug efficacy and patient health” issues, the appropriate approach, at least from the clinical point of view, would be to first look at the research on the topic to determine if a problem exists and then make recommendations (which might include further research).

If the research indicated that casual pill-splitting resulted in dangerously variant doses, perhaps pill-splitting should be recommended only if an accurate pill-splitting device is used. Or, perhaps those medications should be put into liquid solutions that could be measured into precise doses. In any case, the solution is not automatically forbidding a process because one can imagine it potentially causing a danger. If that were so, then all medications would be forbidden, and the pharmaceutical manufacturers would cease to exist.

The writer reveals another motivation (other than the patient’s health) in this statement: “Most people were informed of this money-saving method by their doctors. And this group scores average or better on income and insurance coverage—these folks are less likely to need to save on meds and yet more likely to do so.”

From, again, my own reading of those lines, the writer appears resentful that those who are saving money by pill-splitting could afford to pay full price.

My point is not that pill-splitting is good or bad but rather than the goals of the stakeholders on this issue are not in alignment. Non-congruent goals are not, per se, a catastrophe – unless the causes of those differences are obscured.

Personally, I believe that by pushing pill-splitting as a cost saving mechanism, health plans and clinicians will inevitably force pharmaceutical companies to move from a flat rate per pill pricing to a fee pro-rated by dose. After all, those health plan newsletters notwithstanding, pill-splitting is not an as economic miracle, producing something from nothing. It’s merely a mechanism for taking advantage of pharma’s traditional pricing structure to shift costs from patients and third party payers to the drug companies in a zero sum game.

On the other hand, I also believe that pharma, by casting their disapproval of pill-splitting as purely altruistic concern for the health of the public free of any taint of protecting profit margins, opens itself to accusations of hypocrisy and evokes animosity that patients and clinicians use to rationalize and justify pill splitting (and similar tactics) as no more than the just desserts of the drug companies.

Long before reading this article, I wondered why the drug companies didn’t send health plans a form letter of this sort:

Of course, maybe I’m being naive and missing the point.

Footnotes

1. That the study was a survey that relied on self-report is significant and deserves more emphasis, especially since the findings ascribe motivations to the participants. Compliance studies based on self-report are notorious breeding grounds for face-saving rationales, whether concocted consciously or unconsciously. [back]
2. I suspect the original study is unavailable because it contains proprietary data, but even if it is accessible, the name of the study was not provided and a search based on the information given in the article turned up no results. [back]
3. This kind of variation in definitions of compliance could also have significant impact on research findings [back]

• 98.6% Medication Compliance
• The How To Use Medication Organizers Introduction and Pillbox Pictorial
• Dispensing Pills In Style
• Patient Adherence Decreases Costs But Difficult To Achieve
• More About Government Regulating Healthcare Compliance

There’s No Noncompliance Like Show Business Noncompliance

Eye Fix Backfires On Celebutard
Richard Johnson New York Post January 19, 2007


Although I had not planned to post new material on this blog while reworking the AlignMap.com site, I cannot pass up the opportunity to reference a patient compliance item from the “Page Six” section of the New York Post in timely fashion.




The Background: According to The Post,¹ “The muscles of her [Ms Hilton's] left eye were supposedly damaged” six years ago from surgery she underwent at that time “to lift her lids.”

Treatment Noncompliance:
The treatment compliance issue is addressed in this excerpt:

Hilton … has made things worse by wearing blue- tinted contact lenses over her naturally brown irises. “They have been drying out lately,” dished the tipster. “She is ignoring doctors’ orders to not wear her tinted contacts.” Paris’ rep Elliot Mintz told Page Six, “To the best of my knowledge, Paris has never had any kind of cosmetic surgery and has not mentioned any medical procedures having to do with her eyes.”

Commentary

Yep, it’s AlignMap.com for your complete coverage of patient compliance.²

Footnotes

1. The New York Post’s source is identified as “a Beverly Hills source” [back]
2. Also see Letterman, Pills, & Compliance Enhancement [back]

• Factors In Lifestyle Change
• Cultural Differences & Presumed Noncompliance
• Systemic Alignment
• Organizing Data About Factors That Affect Compliance
• Status Of Improving Patient Adherence To Cancer Treatment Project

From: Jeffrey Nard and Mark Townsend. “Finding the balance in bipolar disorder: focus on mania and safety.” An industry-sponsored symposium presented in conjunction with the U.S. Psychiatric & Mental Health Congress, New Orleans, La., November 16-19, 2006. Reviewed in Diagnosing And Treating Bipolar Disorder By Jeff Minerd. November 21, 2006

While patients and clinicians often assume that medication noncompliance among patients with bipolar disorder, an especially common problem, is typically caused by the the patient’s hope to regain the euphoria associated with manic episodes, this is, according to a survey published in Psychopharmacology Bulletin, the reason least cited by noncompliant patients, being named as the primary cause for noncompliance by only 2% of patients. In comparison, approximately 30% said they failed to comply with medication because of side effects, such as sexual dysfunction and weight gain.

• Asking About Adherence
• Dignity & Adherence
• I Am Non-Compliant And It Sucks
• Insights From CATIE About Noncompliance
• Using Virtual Worlds To Enhance Adherence

Touloumi, G et al. Highly Active Antiretroviral Therapy Interruption: Predictors and Virological and Immunologic Consequences. Journal of Acquired Immune Deficiency Syndromes 42(5): 554-561, 2006.

Findings

The headlines of the stories about this study, including this one, tend toward variations of “One Patient In Six On ART Interrupt Treatment.”

The final paragraph of the original article itself puts it this way:

Commentary

I originally selected this article for my reading list on the assumption that, because its subject was interruptions in treatment, it would include information re the causes of this noncompliance. As it turns out, however, “… reasons for TI [Treatment Interruption] or adherence rates were not available in our study.” This is not only disappointing to those of us interested in patient compliance, but it also results in uncertainty about the ’s findings because it potentially skews the characteristics of the group selected for the study.

The patient data for the study was extracted from the information gathered from the Concerted Action on Seroconversion to AIDS and Death in Europe (CASCADE) collaboration, which included cohorts totaling 8300 seroconverters. Selection criteria follow:

The authors elaborate on the advantages of using the CASCADE data:

These study’s criteria eliminated 6749 of the original 8300 CASCADE subjects. While the remaining 1551 subjects constitutes a respectable N, the results of treatment interruption in those 6749 patients not studied is hardly trivial.

Further, as Bernard points out¹

The investigators only measured clinical progression via the development of a clinical AIDS event, or death. Seven people who did not have AIDS when they began ART developed a clinical AIDS event during their treatment interruption. Eight people who did not have AIDS when they began ART developed a clinical AIDS event whilst on ART. In addition, two people with AIDS when they began ART experienced another AIDS illness during their treatment interruption, compared with one person with prior AIDS who remained on ART. However, the investigators found that there was no statistically significant difference between the rate of developing a new AIDS illness whilst interrupting treatment compared with remaining on ART. ( 0.037 vs. 0.019 cases per person per year; p=0.158). Although the investigators note that nine individuals in the study died without an AIDS diagnosis, they do not provide any further data. Since the SMART study found an increased risk of non-AIDS deaths during treatment interruptions, information on whether these deaths occurred on or off treatment would have been illuminating.

By choosing a subset of treatment-interrupters that accounts for less than 14% of the total patients available and for which information about the reasons for the treatment interruption is lacking while, in effect, eliminating the most noncompliant group of patients from consideration, by not investigating non-AIDS deaths, and by limiting the definition of clinical progression to a clinical AIDS event or death, the study restricts the generalization of its findings.

Consequently, its conclusion that “discontinuing treatment seems to be safe for subjects with a well-retained immune system” appears venturesome, especially given previous studies that indicate an increase mortality rate when treatment is interrupted.

Footnotes

1. Edwin J. Bernard. One-in-six interrupt treatment within two years of initiating ART Aidsmap, September 18, 2006 [back]

• Benefits Of Compliance Enhancement Diminish When Program Ends
• Negative Effect Of Depression On Adherence To HIV Treatment Dissipates With SSRIs
• Meta-Analysis Disputes Assumptions About Nonadherence With HIV Treatment
• Pillbox Organizers May Improve Adherence To HIV Treatment
• HIV Treatment Noncompliance More Likely In Younger Patients

Spotting Noncompliance By Joyce A. Cramer, B.S. Ophthamology Management April 2005

While the article’s focus is ostensibly on adherence to ophthalmologic medications, the principles can be widely applied across many diagnoses and treatments. The prevalence of noncompliance and the problems in recognizing it are discussed with a emphasis on the special difficulty in discovering noncompliance of the sort that occurs when a patient takes her medication erratically or only occasionally.

Common errors in diagnosing noncompliance, such as assuming that well educated patients are less vulnerable to noncompliance and that patients who have a good relationship with the clinician are more likely to be adherent to treatment, are also noted.

Eschewing the equivocation often noted in the clinical literature when considering the topic of compliance measurement, the author declares straightforwardly

The article ends with Ms Cramer planting yet another flag in what has become, justifiably, known as her designated territory – the correlation between simplified medication regimens and higher rates of compliance.

This is an excellent, if not comprehensive, introduction to the challenge the clinician meets on a day in/day out basis in trying to detect and deal with treatment noncompliance.

• Fixes for Today
• Healthcare Cost-sharing And Medication Compliance
• Paris Hilton and Patient Noncompliance
• Noncompliance & Treatment-Resistant Schizophrenia
• Promoting Compliance With Pharmacy Benefit Incentives

Poor breast cancer patient medication compliance highlighted

According to a study to be published in the European Journal of Cancer, 72 of the 131 women interviewed, each of whom were at least two years on from their initial breast cancer diagnosis, stated that they sometimes failed to take their medication. Sixty reported forgot to take their drugs; 12 patients had deliberately chosen not to comply with treatment. Other specific reasons given included difficulty swallowing tablets and the side effects of medication.

Lead author Louise Atkins noted, “The findings are concerning because not taking a full course of medication could impact on how effective a treatment will be,” going on to state, “If we can understand more about the reasons why some women don’t take their medications, then we’ll be in a better position to help women overcome these difficulties.”

According to Professor John Toy, Medical Director at Cancer Research UK,
It is vital that women with breast cancer do not deny themselves the chance of the maximum possible benefit from their medication. It is important that women are as well informed as possible about both the benefits and side effects of their medication and so know what to expect. Clear communication can help to ensure that doctors are better informed about how women are dealing with their treatment so as to help reduce any negative impact that treatments might have.

Commentary

There is little surprising about the noncompliance detected by this study. It is not clear from this preliminary article if there is a specific reason to believe that increased patient information would have a significant impact on adherence in this situation, but, failing that, previous research would suggest that any improvement from efforts to further educate the patient will be minimal.

• Research Examining Culturally Tailored Compliance Enhancement Interventions
• 98.6% Medication Compliance
• Status Of Improving Patient Adherence To Cancer Treatment Project
• Effect Of Targeted Interventions On Patient Compliance With Screening
• Lancet Recommends European Union Mandate Vaccination Against Cervical Cancer Virus

Many HIV Canadians not following drug plan: study
CTV Updated Wed. Aug. 9 2006 11:26 PM ET

Adherence to Antiretroviral Therapy in Sub-Saharan Africa and North America
Mills, EJ, Nachega, JB et al. JAMA. 2006 Aug 9;296(6):679-90.
__________________________________

Mills et al analyzed thirty-one studies on medication compliance from North America (28 full-text articles and 3 abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub-Saharan Africa and found that just 55 per cent of North Americans HIV patients substantially followed their anti-retroviral medication regimens, compared with 77 per cent of their counterparts in sub-Saharan Africa.

Commentary

As Mills points out, the findings dispense with the idea that impoverished and undereducated Africans will inevitably prove unable to adhere to treatment. Compliance just isn’t that simple.

• Pillbox Organizers May Improve Adherence To HIV Treatment
• Negative Effect Of Depression On Adherence To HIV Treatment Dissipates With SSRIs
• Interruptions In Antiretroviral Therapy
• Fees For HIV Treatment Increase Risk Of Death In Developing Countries
• Healthcare Cost-sharing And Medication Compliance

Published Article:
Use of human immunodeficiency virus postexposure prophylaxis in adolescent sexual assault victims
Olshen E, Hsu K, Woods ER, Harper M, Harnisch B, Samples CL.
Arch Pediatr Adolesc Med. 2006 Jul;160(7):674-80.

Release To Lay Press:
Teen sexual assault victims rarely finish HIV-exposure drugs
Advocate.com Reuters. July 15, 2006
________________

Results

The stark numbers of a study by Elyse Olshen & colleagues tell a terrifying story:

• 145 adolescent patients (97% female) seen within 3 days of sexual assault









• 129 were offered HIV postexposure prophylaxis









• 110 agreed to its use









• 86 began the protocol









• 13 completed the full course of treatment

The authors conclude:

Commentary

Given the extreme degree of noncompliance and the long-term risk to these adolescents and to those with whom they come into contact, “patient education” and follow-up programs “to encourage PEP adherence” may not represent a proportionate response to the situation. It would seem that a more aggressive approach, perhaps Directly Observed Therapy, is warranted.

• HIV Treatment Noncompliance More Likely In Younger Patients
• Economics, Gadgets, & HIV Treatment
• HIV Treatment Adherence Resources
• Coerced Treatment Of Tuberculosis & HIV
• HIV Treatment Adherence Online Summary

Fewer Than Half of Adults With Diabetes Get Critically Important Yearly Exams
Medscape Business of Medicine. 2006;7(2) Posted 07/06/2006
_________________________

Data from the United States Department of Health and Human Services’ Agency for Healthcare Research and Quality demonstrate that less than half of adults with diabetes (41.7% ) report compliance in the year preceding the survey with all three of the recommended annual exams:

• Hemoglobin A1C

• Dilated eye exam for diabetic retinopathy or other eye damage









• Foot exam for sores and irritation

An Economic and Health Costs of Diabetes study estimated that $2.5 billion in hospital costs could be saved by preventing complications from diabetes through improved primary care

• The Oath
• The Personal Patient Compliance Project Update
• Medication Noncompliance With Statins - Same Old Same Old
• Fees For HIV Treatment Increase Risk Of Death In Developing Countries
• Smoking Persists Despite Related Diseases

Screening: Older Women May Be Skipping Mammograms
By Eric Nagourney; NY Times June 20, 2006

Older Women Have Far Fewer Mammograms Than They Report
By Joel R. Cooper, Health Behavior News Service June 20, 2006
____________________

Both of these articles report on a study to be published in the August issue of The American Journal of Preventive Medicine¹ that compared Medicare data for mammograms received by 146,669 women ages 65 and older with patient self-reports collected by the Behavioral Risk Factor Surveillance System and the National Health Interview Study for the period between 1991 and 2001.

The trend demonstrated by the results in general can be seen in isolated finding that 70 to 80 percent of women ages 65 to 69 self-reported compliance with receiving a mammogram every two years, but only 61 percent were actually screened.

African-American, Asian-American and Hispanic women in this age group received mammogram screening at even lower rates

The study did not address the causes of this disparity.

Commentary

None of this should be surprising, but it is worthwhile to note another bit of supporting evidence for the prevailing trends in patient compliance:

1. Significant noncompliance exists regardless of age or treatment/screening.
2. Noncompliance is typically (but not always) more pronounced among lower socio-economic and minority groups.²
3. As a instrument for measuring patient compliance, self-report is almost universally unreliable

Footnotes

1. Kagay CR, Quale C, Smith-Bindman R. Screening mammography in the American elderly. Am J Prev Med 31(2), 2006. [back]
2. This is not equivalent to noncompliance being limited to these groups [back]

• Noncompliance Despite Life Or Death Stakes
• Smoking Persists Despite Related Diseases
• Medication Noncompliance With Statins - Same Old Same Old
• Laws & Public Health Compliance
• Once More, Everyone - Not Just The Elderly - Needs A Personal Medication Record