The New York Times On Lipitor Vs Simvastatin Study

11-04-2007 | Categories:


Follow-up To AlignMap Post On Study Claiming Switch From Lipitor To Generic Is Dangerous

Rather than sacrifice blogging’s inherent advantage of timeliness, I’m deferring the promised conclusion and summary post on the Personal Medication Record to link to and comment on this 3 November 2007 New York Times article, Maker of Lipitor Digs In to Fight Generic Rival, by Stephanie Saul And Alex Berenson, which addresses the Pfizer-sponsored statin research project study that was the focus of the 8 September 2007 AlignMap post, Lipitor Would Rather Fight Than (Have Patients) Switch



The article from the Times recapitulates much of argument I made in the earlier blog entry sans my lengthy exposition of some of the study’s problematic methodological issues. The crux of the New York Times essay is congruent with the final line of my post:

The most useful lesson from this study may well be the reminder that certain medical research projects may have as much to do with market share as with morbidity and mortality.

I’ve included a short excerpt of the opening of the article but the full piece is available without charge at ~ Maker of Lipitor Digs In to Fight Generic Rival ~


__________________________


It is shaping up to be the biggest shift yet to a generic drug, potentially saving the nation $2 billion a year or more in prescription costs. And scientists and doctors say that for most of the 16 million people in America who take drugs to reduce cholesterol, the low-priced alternative will work as well as the name-brand medicine — Lipitor, which is made by Pfizer and is the nation’s most widely prescribed drug. While Lipitor itself is not available as a generic, a very similar drug made by Merck, Zocor, lost its patent protection last year. The generic version of Zocor, simvastatin, is now much cheaper than Lipitor, leading insurers to press doctors and patients to switch.
But Pfizer is not letting its flagship drug go down without a fight. The company has mounted a campaign that includes advertisements, lobbying efforts and a paid speaking tour by a former secretary of the federal Department of Health and Human Services. Pfizer is also promoting a study — whose findings many experts are questioning — that concluded that British patients who switched to simvastatin had more heart attacks and deaths than those who remained on Lipitor.





Related Posts:

Does Study Show That Patient Choice Promotes Adherence?

10-09-2007 | Categories:

Patient choice promotes adherence in preventive treatment for latent tuberculosis
T. W. Rennie, G. H. Bothamley, D. Engova, and I. P. Bates. Eur Respir J 2007; 30:728-735






The Study

This study’s abstract follows:

The aim of the present study was to compare the effect of patient choice on completion rates and adverse drug reactions for patients treated for latent tuberculosis infection (LTBI) using 3-month rifampicin and isoniazid treatment (3RH) or 6-month isoniazid treatment (6H).

Data for all patients treated using 3RH or 6H for LTBI between 1998 and 2004 were analysed. In total, 675 patients attended for chemoprophylaxis. Of these, 314 received 3RH and 277 received 6H. From April 1, 2000, patients were offered a choice of regimen; 53.5% completed the regimen successfully, a further 10.3% potentially completed it successfully and 36.2% failed to complete treatment.

Logistic regression analysis suggested that successful completion was more likely in patients who were younger (an association that was lost after removing all patients aged <16 yrs), were offered a choice of regimen and attended all clinic visits before commencing treatment. Treatment was discontinued due to adverse reactions in 16 (5.1%) patients who were prescribed 3RH and 16 (5.8%) who were prescribed 6H. Treatment failure was most likely during the first 4 weeks of treatment for both regimens. At 13 weeks of treatment, more patients taking 6H had stopped compared with those completing the 3RH regimen. Drug costs were greater using 6H compared with 3RH.

In conclusion, offering a choice of regimen improves completion. Most patients chose the 3-month rifampicin and isoniazid treatment over the 6-month isoniazid treatment. Adverse drug reaction rates between the two regimens were similar.


Commentary

Offering patients treatment choices may indeed promote adherence, but I’m not convinced the results of this study are evidence of this hypothesis.

First, the study is complex. The population included patients treated by one of two methods, 3 months of rifampicin and isoniazid or 6 months of isoniazid, over a six year period. During the first two years, the treatment for a given patient was chosen by the doctor (the reasons one method or the other was chosen were not provided) while the patients were offered their choice of treatments over the last four years of the study.

That the majority of patients (78%) chose the shorter treatment is hardly surprising. (Nor is it surprising that more patients completed a three month course of treatment than a six month course of treatment.) Since the split between 3 month treatments and 6 month treatments among all patients was almost equal (3 month treatment: 53% of patients; 6 month treatment: 47% if all patients) the majority of the physician-assigned patients must have received the longer treatment.

I suggest that conclusions based on comparisons between these inherently dissimilar groups are, at best, tenuous.

Further, as is often the case in compliance studies, the definitions of successful completion, potentially successful completion, and failure to complete are rational but somewhat arbitrary:

… a Successful completion required attendance to all outpatient appointments with affirmative objective observations (urine tests) and evidence of tablet taking. Potentially successful completion was defined as a missed
appointment or a single negative urine test fully explained by the patient, and sufficient medication supplied to ensure that
there were no gaps in treatment. Failure to complete included the remainder, i.e. those who defaulted from clinic visits
without sufficient medication to ensure treatment completion.

And, for the purposes of this study’s statistics,

To perform binary logistic regression, ‘‘potentially successful completion’’ was categorised as ‘‘failure’’ in order to create a dichotomous variable; successful completion in these patients could not be assumed.

While these decisions can be justified and, indeed, may be necessary, it is unlikely that the definitions of adherence and nonadherence used in this research are a perfect match for the notions of adherence and nonadherence used in everyday clinical practice.

There are other, less overt, problems with this study enroute to the conclusion that patient choice enhances compliance but these should be sufficient to cast doubt on the unequivocal declaration of the title. A shame, that.





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Lipitor Would Rather Fight Than (Have Patients) Switch

09-08-2007 | Categories:


The Story & The Study

Reading the 6 September 2007 Medication Noncompliance blog entry, Pfizer Funded Study Says: Don’t Stop Taking Your Lipitor!,1 alerted me to an intriguing Pfizer-sponsored statin research project and the presentation of its findings carried in multiple print and internet outlets.


Points of Intrigue

What is there, one might ask, about this study of statins that could be called intriguing?

Well, one intriguing point is that the first dozen or so articles on a Google search for “Pfizer,” “Lipitor,” and “simvastatin” referencing this study contain almost identical text taken from a press release put out by Pfizer - which may explain why Reuters, the first source I found after reading the Medication Noncompliance post, published the article under the title, Patients Who Switched from Established Lipitor Therapy to Simvastatin Experienced a Significant 30 Percent Increase in Relative Risk of Cardiovascular Events or Death, New Observational Study Shows, a rather longish headline that nonetheless effectively conveys the pro-Pfizer interpretation of the results conveniently uncluttered by any messy details and disclaimers.

A second intriguing point is that, although the study would certainly be categorized as medical research, was presented at the European Society of Cardiology Congress, and is to be published in The British Journal of Cardiology, most of these outlets carrying news of the study positioned it in the investment and business divisions of their web sites, as indicated by the domain and subdomain names of the pertinent URLs assigned to the articles, including, among others, biz.yahoo.com, money.cnn.com, www.forbes.com, finance.google.com, today.reuters.com/stocks, news.moneycentral.msn.com/ticker, www.quote.com. The story also received considerable play in the newsletters and sites covering the pharmaceutical industry (e.g., Drug Industry Daily and Pharmaceutical Business Review). Reportage of the study at clinically oriented sites (e.g., WebMD - which did not quote extensively from the press release) was notably less extensive.

Clearly, there is nothing illegitimate about a consideration of the business implications of medical research findings (or, for that matter, distributing press releases on the occasion of favorable news for the sending entity); I only suggest that garnering an understanding of this study and others like it might be abetted if its commercial aspect and its marketing spin are taken into account.

The clinical and marketing motivations for the study almost assuredly originate from the ramifications of the same historical event: Zocor, the branded version of simvastatin, a statin found to have been an effective agent albeit one somewhat less powerful than Lipitor, lost its patent protection in June 2006. Consequently, the price of this medication dropped significantly, causing a significant fraction of Lipitor users to change their medication to generic simvastatin, a shift encouraged and called for by certain third party payers, physicians, and patients themselves.

Pfizer, unsurprisingly, has questioned the clinical wisdom of patients migrating from their product, Lipitor, to a generic drug.2 For a congruent but more fiscally eloquent explanation, consider this excerpt from Fighting the Generics Next Door published 7 September 2007 at The Motley Fool:

The introduction of a generic alternative can kill a blockbuster drug’s sales faster than Nicole Richie can get out of jail. But losing a patent might not just hurt sales of the covered drug; it also affects competitors because patients will switch from a brand name to a competitor’s generic. Pfizer (NYSE: PFE) is trying to fight the slide in sales of its patented Lipitor, as some patients switch to generic versions of Merck’s (NYSE: MRK) Zocor, made by Teva Pharmaceuticals (Nasdaq: TEVA) and other firms. The company didn’t run a major double-blind clinical trial to compare the two — that would be way too expensive. Instead, Pfizer did an observational study of a database of 11,520 patients, some of whom had switched to generic Zocor and some who had remained on Lipitor.

“Observational study” means the researchers reviewed records of patients who in the past took Lipitor, some of whom switched to simvastatin. Retrospective studies of this sort typically lack certain desirable qualities of prospective studies, such as randomization of patients, control of variables, and complete pertinent information. In this study, as the report notes, “Reasons for why treatment was discontinued were not available from the database, Pfizer indicated, adding that reasons for switching from one drug to the other were also not available. Furthermore, Pfizer explained that patients in the study were not randomised to each arm, which limits the significance of the findings.”

The non-randomized sample means that the two comparison groups, Lipitor-Continuers and Lipitor-Switchers, were not necessarily comparable. One detail , for example, from the poster session that didn’t make its way into the press release is that, as reported in Cholesterol Drug Change May Be Risky, “as a group, the patients who remained on Lipitor also took more heart medications and had better cholesterol control to begin with than the patients who switched to simvastatin,” a fact that could go far to explain the difference in outcomes.

The Patient Compliance Angle

The significance of the conclusions was especially limited for me since my personal interest in this study arose from a secondary finding:

A secondary analysis demonstrated that patients who changed drugs were more than twice as likely to discontinue treatment, compared with those who stayed on Lipitor.

Without knowing why the treatments were discontinued or why the patients were switched, this finding is interesting in a “how about that?” sort of way, but almost worthless for generating hypotheses or useful clinical practices.

Possible reasons for the higher noncompliance rates among the patients who switched medications are easy and fun to generate; how about these three for starters:

  1. Patients switched because of the cost of medication. Those same patients who switched from Lipitor might well have been those individuals most likely to discontinue medication altogether for financial reasons - even though if the cost of simvastatin were relatively less than that of Lipitor.3
  2. Patients switched because of side-effects of Lipitor. Those same patients might well have proved more vulnerable or less able to tolerate side-effects of other statins as well, including simvastatin.
  3. Patients switched because of unresponsiveness to Lipitor. The departure of these patients from the Lipitor-taking group would immediately improve the outcome statistics of that category of patients by eliminating their negative results. Moreover, they could well have been more likely to be unresponsive to any statin and thus increase the apparent cardiovascular risk of the “Switched To Simvastatin” group.

Also, while the number of patients who discontinued treatment altogether is given, the actual compliance rates of those who continued treatment with either drug isn’t provided. (In other words, it isn’t known how many patients who continued to be enrolled in treatment with Lipitor, for example, actually took clinically effective doses of that medication, how many took the medication erratically, and how many professed to be taking the medicine but, in fact, were taking none.) Consequently, the effectiveness or ineffectiveness of taking adequate doses of Lipitor and simvastatin is impossible to calculate with confidence.


The Lipitor Challenge

If the study’s design is a researcher’s nightmare, it is a marketer’s delight.

Remember the “Pepsi Challenge” ads that showed blind tastings of Pepsi and Coke by cola drinkers with a stated preference for Coca-Cola? The design of that survey virtually guaranteed a good outcome for Pepsi - if even 10% of those tested, a number probably within the statistical error of the study, had chosen Pepsi, it would have been a triumph for that brand since those were ostensibly hard-core Coke drinkers.

The design of the “Stayed With Lipitor Vs Switched To Simvastatin” study similarly stacks the odds in favor of Lipitor. For one thing, it’s generally acknowledged that Lipitor is more effective than simvastatin; the question is whether the difference justifies the higher cost. So, from the outset, it was clear patients on Lipitor should have had better outcomes. It also seems likely that those patients who remained on Lipitor rather than switching were responding adequately or at least their doctors saw no benefit in moving them to a different drug. As suggested before, patients who switched from Lipitor might well be more likely noncompliant with, vulnerable to side-effects of, or unresponsive to other statins.

But the real clinker to those who don’t follow statin clinical research may be the consensus of earlier studies that discontinuation of any statin increases cardiovascular risk.

For example, New evidence links discontinuation of statin therapy to increased death rates in stroke survivors reports on a study in Stroke: Journal of the American Heart Association that demonstrated that “patients who stop taking cholesterol-lowering drugs within a year of surviving a stroke had a two-fold increased risk of death.”

“To the best of our knowledge, this is the first evidence linking discontinuation of statin therapy to increased death rates in stroke survivors who have no other clinical evidence of heart disease,” he and colleagues wrote. Statins effectively lower blood levels of low-density lipoprotein cholesterol (LDL), known as “bad” cholesterol. The drugs have major side effects. “Patients who stop taking the statins have a significantly increased chance of death in the first year after their stroke - and the earlier they stop, the higher the risk they face,” Colivicchi said. “In fact, the risk factors for the association between statin discontinuation and death gradually decreased with time. Effective clinical strategies are needed to bring out a significant increase in patients who maintain their drug therapies.”

And Statin Withdrawal Hard on the Heart - Discontinuing Statins Can Lead to Rapid Rise in Cholesterol and C-Reactive Protein notes

Stopping cholesterol-lowering statin drugs after long-term use packs not one, but two potentially deadly punches to the heart. That’s the bottom line of a new study that shows that people who discontinued taking the drugs experienced rapid rises in both C-reactive protein (CRP) and LDL cholesterol levels. These data provide support for the acute increase in cardiovascular risk associated with statin discontinuation, they write.Statins lower not only cholesterol, but also reduce CRP, a marker of harmful inflammation in the arteries that can lead to blood clots, says researcher Folkert Asselbergs, MD, PhD, of the University Medical Center Groningen in The Netherlands. Dozens of studies have now shown that CRP, like cholesterol, is an important, independent predictor of heart attack and stroke risk, he says. “If you stop statins, it’s a double whammy,” Asselbergs tells WebMD. “Statin withdrawal leads to a rapid and significant increase in CRP, independent of the parallel LDL increase. “If you’re on a statin, keep on your medication!” he says.

So, there would seem to be a reasonable chance that if Merck & Co had sponsored research looking at patients who switched from Zocor (assuming Zocor were still under patent - and incredibly profitable) to a generic form of Lipitor (or any other statin), the headline could have been “Patients Who Switched from Established Zocor Therapy to Atorvastatin Experienced a Significant X Percent Increase in Relative Risk of Cardiovascular Events or Death, New Observational Study Shows.”

Now, that would be an intriguing study, eh?


Conclusions

Maybe there is something especially catastrophic about shifting from Lipitor to simvastatin - or maybe not. In any case, nothing in this research proves either side of the debate. The findings do seem in line with the concept that discontinuing statins places patients at much higher cardiovascular risk, which is helpful but hardly groundbreaking.

The most useful lesson from this study may well be the reminder that certain medical research projects may have as much to do with market share as with morbidity and mortality.



Footnotes


  1. I view the take on this study espoused in the Medication Noncompliance post reasonable, informative, and, as always, interesting, but, on the whole, lacking in the kind of embittered cynicism characteristic of the AlignMap perspective. Welcome to the Dark Side. [back]
  2. I am not the originator of this concept; The New York Times, for example, in its October 15, 2005 article, Lipitor or Generic? Billion-Dollar Battle Looms, predicted this sort of thing almost a year before Zocor’s patent protection expired. [back]
  3. While relative cost of these medications is now a primary issue, this is an unlikely cause of switching in this study, given that the observational period was from October 1997 to June 2005, a period during which Zocor was still under patent and, presumably, did not cost markedly less than Lipitor. [back]



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Adherence Research Needed In Poorer Countries

07-24-2007 | Categories:

Adherence to Treatment in Poorer Countries: A New Research Direction? Alison Breen, M.A., Leslie Swartz, Ph.D., John Joska, M.B.Ch.B., F.C.Psych.(S.A.), Alan J. Flisher, Ph.D., F.C.Psych.(S.A.) and Joanne Corrigall, M.B.B.Ch., D.M.H.(S.A.) Psychiatr Serv 58:567-568, April 2007






The Letter

This letter to the editor points out the obvious but often overlooked fact that “most studies of treatment adherence have been conducted in high-income countries and the question arises as to whether there are structural barriers to adherence that are particular to, but underresearched in, areas with poor resources.”

The authors looked at a qualitative study of ten cases conducted in South African households with members who were caring for a household member who had schizophrenia and living in poor urban environments. Several themes were identified indicative of the particular healthcare compliance problems that challenge the poor.

Several logistic problems were described by patients and relatives, including having to queue in darkness outside the clinics from as early as 4 a.m. and having to wait for many more hours before they could collect their medication. Participants spoke of the high risk of being mugged and attacked while waiting in the queues. Participants also told stories of how patients waiting in queues would become impatient and leave before collecting their medication, thus defaulting on their treatment. One coping strategy used by patients was not taking the correct dosage of their medication—for example, taking one pill instead of two, so that a clinic visit was required every two months instead of every month.


Commentary

The factors affecting compliance seem never-ending. Nonetheless, as the authors of this letter point out, poverty inflicts special problems on a large number of patients and research efforts in this area are essential - for all of us.





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Seasonal Effect On Compliance With Diabetic Treatment

06-27-2007 | Categories:


Roman mosaic of the Four Seasons from the House of Bacchus in Complutum
(Alcalá de Henares, Madrid, Spain). Late 4th century A.D.


Progress Toward Diabetic Treatment Goals

Source: Diabetes Patients Make Significant Gains in Disease Control; Still, Nearly Half Fail to Reach ADA Treatment Goals

According to the Quest Diagnostics Health Trends Report on Diabetes,1
presented on 23 June 2007 at the ADA Annual Scientific Conference (posters # 21-LB and 22-LB), Americans being treated for diabetes improved control of their disease over the last six years, by 44.4%.

As of December, 2006, more than half (54.6 percent) had reached treatment goals for glycemic control, established by the American Diabetes Association (ADA), compared to 37.8 percent in 2001. This finding is a Despite these overall gains, hemoglobin A1c (HbA1c or A1c) values have plateaued since 2004 with 45 percent of patients in 2006 failing to reach treatment targets of HbA1c levels less than seven percent.

Seasonality

This excerpt from the article address seasonality of compliance:

A companion analysis of HbA1c tests revealed a significant seasonal variation in blood glucose control with HbA1c levels peaking in the winter (January-March) and falling in the summer (July-October.) These seasonal differences depended on patient age and level of A1c control, but were most apparent in the elderly (greater than or equal to 80) and those with the highest levels of HbA1c (greater than or equal to 9 percent).

Commentary

While I am uncomfortable presenting an issue based exclusively on a press release from a company intimately involved in accumulating the data, I am struck by the seasonal variation in results, a trend rarely considered as a factor in patient compliance.

This excerpt touches on the implications of the findings:

“The HbA1c plateau mirrors the clinical progression of the disease and treatment patterns,” said study co-author Richard W. Furlanetto, M. D. Ph.D., medical director, Endocrinology, Quest Diagnostics, Nichols Institute. “The newly diagnosed patient tends to be diligent and first-year treatment tends to be aggressive, so we often see relatively large improvements in blood sugar control and HbA1c levels. In subsequent years the diabetes itself worsens and the therapy gets less effective. Also, as blood sugar control improves, the risk of hypoglycemia or low blood sugar, increases and this limits therapy. Finally, over time patients may become less diligent in following their treatment plan. It is in these post-diagnosis years that we must stress patient monitoring and treatment compliance,” Furlanetto continued.
The seasonality shifts are among the most striking finding in the data, authors said, and may allow physicians to exert more control over testing and treatment schedules. According to study authors, serial HbA1c levels should be obtained in late spring and autumn to minimize the impact of seasonal fluctuations on the interpretation of HbA1c levels.

Life course and seasonality may be as important in the context of adherence as they are in chronic disease. Certainly, this could be a rewarding focus for future research.



Footnotes


  1. The Quest Diagnostics Health Trends Report on Diabetes is based on findings from 22.7 million de-identified HbA1c tests, a key indicator of diabetes control, performed by Quest Diagnostics between 2001 and 2006 on 4.8 million patients who saw a healthcare professional and were classified as having diabetes. [back]



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Status Of Improving Patient Adherence To Cancer Treatment Project

04-02-2007 | Categories:

I am remiss in not already posting this follow-up to an earlier post, Research Examining Culturally Tailored Compliance Enhancement Interventions. I had emailed the primary author, Dr. Katherine Ell about the status of Improving Patient Adherence To Cancer Treatment and when it was scheduled for completion and publication.

Dr. Ell’s gracious and prompt reply explains that the study has been completed and work is currently focused on the adherence outcome analysis paper.

She goes on to note that the adherence rates for both the intervention and control groups are remarkably high, above 90 percent for chemotherapy and radiation therapy although adherence to post-treatment follow-up is lower. Consequently, there are no significant differences between groups.

The study population is low-income, and the qualitative studies indicate a key factor in adherence seems to be the availability of the Cancer Treatment Fund which went into effect in Jan 2002 at the start of our clinical trial. The data also show that cost concerns were very high at baseline for both groups.

Finally, Dr. Ell points out that she and her colleagues will later examine other quality of life outcomes.




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Research Examining Culturally Tailored Compliance Enhancement Interventions

03-19-2007 | Categories:

Improving Patient Adherence To Cancer Treatment Ell, Kathleen R. Cancer Control Research; National Cancer Institute



Improving Adherence To Cancer Treatment

Excerpt From Abstract of Proposal:

Studies of adherence to cancer treatment find that low-income and minority population experience important barriers (including access barriers) to optimal treatment adherence behavior (helping to explain less favorable morbidity and mortality cancer outcomes among women living in poverty). A randomized clinical trial is proposed to test the efficacy of a multifaceted intervention on patient adherence to breast and gynecological adjuvant cancer treatment and post-treatment follow-up among low-income minority women. The proposed study will test the efficacy of a culturally tailored intervention model that combines interactive health education (decisional support), counseling (emotional support), and systems navigation (resource access) interventions that have been shown to be effective in enhancing adherence to abnormal screening diagnostic follow-up among low-income minority women. The efficacy of IMPAACT1will be tested by comparing adherence outcomes between intervention and modestly enhanced usual care group patients. The nature of relationships between assessed barriers, adherence outcomes, and quality of life outcomes and patient satisfaction with the intervention and with their cancer care will be identified. In addition, the study will test models specifying direct, indirect, and intervening relationships between assessed barriers and adherence behaviors within intervention and control groups. In addition, estimates of direct costs of the intervention and usual care arms will be compared.


Commentary

While this research is, as far as I can determine, ongoing and no preliminary report has been issued,2 the paucity of clinical investigations of culturally tailored interventions to enhance compliance - and, more pertinently, tailored compliance enhancement methods of any sort - prompts me to note this project’s existence and express hopes that results will soon be available.



Update: Information about the status of this project obtained via personal communication with the project’s Director is available at Status Of Improving Patient Adherence To Cancer Treatment Project



Footnotes


  1. Although it is not specified in the abstract, I assume IMPAACT refers to Improving Patient Access and Adherence to Cancer Treatment, the National Cancer Institute-funded clinical trial of a system of structured interventions based on the case management model applied to 500 women with breast or gynecological cancer with the goal of improving compliance to cancer treatment. [back]
  2. I did find (1) a reference to a presentation, “IMPAACT: Improving Patient Access and Adherence to Cancer Treatment. Barriers to Treatment Adherence in Minorities and Persons Living in Poverty” at the National Institutes of Health Conference, Bethesda, Maryland, February, 2006, but was unable to locate any publication of this material and (2) a summary of a presentation, Reducing Disparity in Recruitment of Ethnic Minority Patients in Cancer Clinical Trials: A Priority in Enhancing Culturally Competent Practice made 13 January 2007 at the Society for Social Work and Research meeting, Bridging Disciplinary Boundaries. That paper, however, addressed “socio-culturally grounded strategies to enhance the recruitment of low-income, predominantly Latina women with cancer that have resulted in relatively high rates of participation in two NIH funded clinical trials of social work interventions.” [back]



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Medication Compliance Research Review

11-17-2006 | Categories:

Medication Compliance Research: Still So Far to Go Albert I. Wertheimer, Thomas M. Santella Journal of Applied Research in Clinical and Experimental Therapeutics 2003; 3(3): 254-261.



The authors have compiled the compliance research, dividing it into six categories:

  1. Articles identifying adherence as a problem
  2. Articles identifying the causes of noncompliance & exploring solutions
  3. Articles analyzing adherence with respect to specific ailments
  4. Articles exploring the patient’s role with respect to compliance
  5. Articles exploring the pharmacist’s role with respect to compliance
  6. Articles exploring the physician’s role with respect to compliance

The bulk of this article deals with the prevalence, incidence, and costs of noncompliance; examples of the compliance enhancements currently available; the theoretical models of medication compliance; and the incapacity of the healthcare professions to effect positive changes.

The conclusions are disheartening.

… one can only conclude that there is still no real consensus concerning the most effective way to improve patient compliance. The research shows that adherence to medications is not routinely measured in clinical practice and a universal standard that can easily be implemented does not exist

The final recommendation is limited to

… perhaps it is reasonable to shift our focuses to the other side of the patient diad: the practitioner. From the literature, we know that the there exists an almost overwhelming amount of information on ways for physicians to improve compliance through establishing better communication techniques. We also know that among the many different communication techniques proposed, none clearly stands out as a clear method for improving patient compliance consistently. We know that the more time physicians give to improving their patients’ compliance, the more effective their efforts are. We know that an increase in the role of the pharmacist improves compliance. We know that telephone and mail-card reminders alone show no real significant improvement in patient compliance.


Commentary

This article is useful as a survey, but its categorization of articles seems arbitrary and of minimal utility. Similarly, the recommendation that research focus on the clinician is followed not by an explanation or support but by confessions that previous studies provide little direction for this tack.




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Fear (Not So Much A) Factor

10-03-2006 | Categories:

Fear Is a Weak Motivator Shankar Vedantam, Washington Post September 29, 2006


This article reaffirms what we have known for some time, both from general psychological studies and clinical trials focused on decision-making:

Scaring people about the health risks of smoking and obesity or the environmental consequences of pollution is an ineffective way to change their behavior, according to a wide-ranging analysis of studies into what works — and what does not — in getting people to live healthier lives and treat the environment more responsibly.

While it’s not quite that simple and, indeed, both fear of consequences and hopes for a better outcome can be motivating in specific circumstances, the point is that the typical health-oriented public service announcement evokes doom and catastrophic outcomes if one does not abstain from drugs, alcohol, fatty foods, unprotected sex, … and the most common clinical advice about compliance is scarcely more sophisticated than adhere to treatment or else. And while those approaches successfully generate anxiety and fear, they rarely improve treatment implementation.

This “analysis of hundreds of research studies involving 47 different kinds of behaviors” indicates that enhancing confidence and poviding tools for setting and reaching goals are more effective.




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Noncompliance Despite Life Or Death Stakes

09-29-2006 | Categories:

People Often Forgo Using Lifesaving Beta Blockers Despite Health Insurance
09/12/2006

This primary finding of the study summarized in this article, 1 that “[f]ewer than half of the patients who were prescribed beta blocker drugs following a heart attack and who had some prescription drug coverage were regularly taking them during the first year after leaving the hospital,” is hardly surprising and is , indeed, congruent with the results of many other clinical studies dealing with medication compliance.

It is nonetheless an important reaffirmation of the extent of the noncompliance with a medication regimen proven in clinical trials to be effective because of the size and extent of the study (17,000 patients followed for one year after suffering a heart attack). The data was obtained from aggregate data contributed by health plans participating in the Council for Affordable Quality Healthcare.

Other useful findings include

  • The largest decrease in adherence occurring during the first month post-discharge
  • Noncompliance was prominent even though patients had prescription medication insurance coverage
  • Younger women with commercial insurance were more likely to fall prey to noncompliance than men their age and older women

Study leader, Judith Kramer, M.D. suggests that “[s]trategies to maintain adherence must focus not only on community physicians to maintain prescribing, but also on patients and their families, and as our results suggest, these strategies need to begin within the first month or two after hospital discharge.”

Footnotes


  1. The study itself is published in the September 2006 issue of the American Heart Journal [back]



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Knowledge & Insight

08-17-2006 | Categories:

Treatment adherence in psychosis From Bandolier, Dec 2003



This Bandolier article, published in the journal in Dec 2003, focuses on one review,1 which found that one patient in four with a psychiatric diagnosis is noncompliant with medications.

To a large extent, in fact, the Bandolier article focuses on the methodology of the review and the studies it encompasses.

Pertinent Points

  • Studies, all of which dealt with adherence of patients with a severe mental disorder, covered by the review dated from 1980, but the date of the last search was not given. For the purposes of the review, non-adherence was defined as either not taking drugs as prescribed or not keeping appointments as scheduled. Significantly, however, any method of specifying adherence Vs non-adherence was allowed.
  • Of the 103 studies (24,000 patients), half had fewer than 100 patients; the majority of patients (84%) were in studies with more than 150 subjects. This becomes important because trial size turns out to be a major factor in calculating the rates of non-adherence. (The overall weighted mean rate of non-adherence was 26%, where weighting was by size of study. The unweighted average was 38%.), with much lower rates of non-adherence in the bulk of patients in studies with more than 151 patients, whether or not weighting was used.

Findings

As the Bandolier authors note,


Knowledge is good, methodological insight is better. This study gives us both.

The knowledge, as already noted, is that about one in four patients with severe mental illness is non-adherent, regardless of specific psychiatric diagnosis.

The methodological insight is that that trial size may be even more important than previously assumed, that rather than being the difference between a good study and a better study, size may be the difference between accurate and misleading results. That small studies produced much higher non-adherence rates. The authors point out that this may indicate that small studies could have other problems that make them less reliable.

Footnote


  1. M Nosé et al. How often do patients with psychosis fail to adhere to treatment programmes? A systematic review. Psychological Medicine 2003 33: 1149-1160. [back]



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Meta-Analysis Disputes Assumptions About Nonadherence With HIV Treatment

08-11-2006 | Categories:

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.
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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.




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