Pharmacology & Pharmacy, 2011, 2, 168-172
doi:10.4236/pp.2011.23024 Published Online July 2011 (http://www.scirp.org/journal/pp)
Copyright © 2011 SciRes. PP
The Impact of a Drug Safety Warning on
Discussions between Doctors and Their Patients;
the Case of Rosiglitazone
Department of Family & Commu nity Medicine, University of California, Davis, United States.
Received April 7th, 2011; revised June 20th, 2012; accepted June 30th, 2011.
The goal of this study was to track the influence of a highly publicized report on discussions between doctors and their
patients and prescribing decisions made in response to concerns about potential medication adverse side effects. This
was a retrospective analysis of a primary care network’s electronic medical record database. From a diabetes registry
of 12, 246 patients, 329 were identified as taking rosiglitazone prior to the June 14, 2007 release of an article in the
New England Journal of Medicine; the article suggesting an increased risk of myocardial events. The entire content of
all office visits, telephone messages, and medication lists for each patient were reviewed over a 2-year period subse-
quent to the article’s publication. Doctor/patient discussions regarding concerns for rosiglitazone were catalogued
including the physician’s treatment reco mmendations. There were documented discussions on rosiglitazo ne’s potential
adverse side effects for 64 patients; 19.5 percent of this population. All of the discussions occurred between June 15 and
October 30, 2007. Of the entire group, 59.3 percent (N = 195) remained on rosiglitazone. For those advised to continu e
rosiglitazone, the provider indicated that he/she wanted more data before determining if the drug was not safe or dis-
counted the validity of the safety concerns. For those advised to discontinue rosiglitazone, 112 (83.6 percent) were
placed on pioglitazone. An article suggesting potential adverse effects of rosiglitazone resulted in a documented discus-
sion in 19.5 percent of patients on this medication. These findings suggest an awareness o f this publication by patients,
presumably derived from media reports. However, an awareness of this concern did not result in a substantial change
in practice. The majority of patients rema ined on rosiglitazone. The content of these discussions suggest th at most phy-
sicians’ recommended waiting for more published data before con sidering a change. While many factors in fluen ce phy-
sician’s prescribing behavior, this study demonstrates how a highly publicized report influ ences the doctor/ patient di-
Keywords: Drug Safety, Patient-Physician Relationship, Rosiglitazone
Thiazolidinediones (TZDs) have been recommended as
part of the treatment plan for patients with Type 2 diabe-
tes (DM). Rosiglitazone and pioglitazone are currently
approved in most countries either as monotherapy, in
combination with sulfonylureas or metformin, or in
combination with in sulin. In comparison to sulfonylureas
and metformin, TZDs have a modest impact in decreas-
ing glycosylated hemoglobin (A1C); the mean decrease
in A1C ranging from 0.7% to 1.6%. Common adverse
side effects from TZDs include weight gain, fluid reten-
tion, and edema. Serious side effects have been reported
and include hepatotoxicity and congestive heart failure
. On June 14, 2007 the New England Journal of Me-
dicine published a report on the potential adverse side
effects of rosiglitazone. The key finding of this article
was as follows: “Rosiglitazone was associated with a
significant increase in the risk of myocardial infarction
and with an increase in the risk of death from cardiovas-
cular causes that had borderline significance” .
Reports of potential harm from medications can be
disseminated rapidly from the index researcher, through
the scientific literature, media channels and then to phy-
sicians and the general public [3 -5]. For specific medica-
tions, the impact of these reports is well-documented and
may have a substantial effect on physician prescribing
behavior. Notable examples of this have included the
The Impact of a Drug Safety Warning on Discussions Between Doctors and Their Patients; the Case of Rosiglitazone 169
impact of trials on utilization of hormone replacement
therapy (HRT) and cyclooxygenase-2 (COX-2) inhibitors
[3-5]. How physicians perceive the effect of a drug
warning published in the medical literature, what actions
they take and how patients respond to these concerns has
not been well studied. There are few studies describing
the impact of a drug warning on the dialogue between
doctors and their patients and the subsequent treatment
decisions. Tracking discussions between doctors and
their patients and the actions taken in response to these
concerns can add to our understanding of what influ-
ences prescribing decisions. The purpose of this study
was to describe the specific discussions between doctors
and their patients that occurred after the dissemination of
this New England Journal of Medicine report and the
actions taken in response to the discussion.
A retrospective analysis was performed using the UC
Davis Health System’s (UCDHS) electronic medical
record (EMR) database (Epic, Verona, WI). Patient data
were obtained by querying the EMR database. This da-
tabase has been previously validated for its accuracy in
identifying all UCDHS patients with DM and in its abil-
ity to produce outcome-specific reports . A search was
conducted for all patients on avandia, avandamet, or ro-
siglitazone for the time period of June 1, 2006 through
June 1, 2007. A report was generated with each patient’s
name and medical record number. The entire content of
all office visits as well as phone messages, medication
lists, medication orders were reviewed for one year prior
to and two years after the New England Journal of Medi-
cine report. Physician comments about rosiglitazone
were cataloged verbatim along with the treatment plan;
to continue the drug or to switch to another agent. Pa-
tients with no evid ence of ongoing clinical activity with -
in the past calendar year; i.e. no office visits, telephone
messages, or evidence of any refill requests were not
included in the study. This work was approved by the
UC Davis Institutional Review Board.
Summary of results from the electronic patient registry;
those who were initially on rosig litazone before the New
England Journal of Medicine article, those who remained
on it for the 2-year observation period, and those who
were switched to pioglitazone is presented in Figure 1.
There were 12,246 patients with DM treated at 13
UCDHS primary care clinics by 66 family physicians
and general internists. There were 355 patients listed as
Figure 1. Summary of results from the electronic patient registry; those who were initially on rosiglitazone before the New
England Journal of Medicine article, those who remained on it for the 2-year observation period, and those who were
switched to pioglitazone.
Copyright © 2011 SciRes. PP
170 The Impact of a Drug Safety Warning on Discussions Between Doctors and Their Patients; the Case of Rosiglitazone
being on rosiglitazone on the May 30, 2007 registry re-
port. Twenty-six of these patients had no evidence of
ongoing clinical activity for the prior year and were re-
moved from the study. There were 329 (2.7 percent of
the total patient population) active patients on rosiglita-
zone as of this date. Of these 329 patients, 64 (19.5 per-
cent) had documented subsequent discussions on rosigli-
tazone’s potential adverse side effects. All of these dis-
cussions occurred between June 15 and October 30, 2007.
Of the entire group, 195 patients (59.3 percen t) remained
on rosiglitazone. For those advised to continue rosiglita-
zone, the provider indicated that he/she wanted more
data before determining if the drug was not safe. For
those advised to discontinue rosiglitazone, 112 patients
(83.6 percent) were placed on pioglitazone. Representa-
tive dyad comments documenting a dialogue between
patients and their physician about safety concerns are
presented in Tab le 1. All comments are extracted verba-
tim from the medical record. These comments are or-
ganized into four categories based on whether there is a
documented patient concern, physician response, and
whether the rosiglitazone is or is not continued .
This study explored the effects of a highly publicized
report on the potential adverse side effects associated
with rosiglitazone. There were two main pu rposes to this
project: 1) To document the types of discussions between
doctors and their patients, and 2) To assess whether there
was any change in prescrib ing.
There was documentation in the medical records in
19.5 percent of patients on rosiglitazone. All of these
discussions occurred within an 18-week period. For the
59.3 percent of patients advised to continue rosiglitazone,
two themes emerged from the documented comments.
First, the provider wanted more data before determining
if the drug was not safe. Second, the provider discounted
the validity of the New England Journal of Medicine
Table 1. Representative dyad comments documenting a dialogue betw een patients and their phy sician about safety concerns.
All comments are extracted verbatim from the medical record.
There is a documented patient concern and the patient remains on rosiglitazone
Patient Statement Physician Response
Patient wants to know if she should continue avandia. Told by another MD
to stop it Recommend to continue
Wife called with concerns Set up a long discussion; re: risks. Patient decided to stay with Avandia
Concerned about TV ads about MI as side effect As a rule we are not stopping Avandia
Concerned about TV ad about avandia’s safety Cont avandia
Hearing bad things about Avandia; wants opinion. FDA reviewing; as of now safe; continue drug.
Heard news report about side effects Spoke with her and will wait and see instead of c h a ng i ng to actos
Heard about concern. They are investigating hasn’t been pulled off shelves; should continue.
Pt stated FDA stated increased risk of death/wants to know if should con-
tinue. Avandia is safe/continue the med
FDA indicated avandia is associ a ted with increased risk of heart attackI feel it is safe and will not discontinue it
There is no documented patient concern and the patient remains on rosiglitazone
Discussed risks and benefits of avandia; does not want to start s h ort acting insulin at this time
Will continue avandia given great contr ol
I had a lengthy discussion of risks/benefits of avandia; pt opted to continue avandia.
Pt ed regarding possible cv side eff e c t s o f a v a n d i a . Will stay on it because it works. Counseled on risks/ben of avandia; discd with family the study.
She will cont for now. Benefits outweig h r i sk s
This complaint about increased risk of MI with avandia contra dicts 2 recent studies. As of now medication is safe.
She is made aware of risk of cardiac problems; in spite of this she would lik e to s ta y o n it .
Discd nejm on cv risks; but alternatives not really good for her. Wil l c on tinue for no w .
Patient education regarding the possible cardiovascular side effects of avandia. Wi ll stay on it because it works. Will pray about decision for insulin
There is a documented patient concern and the rosiglitazone is discontinued
Patient Statement Physician response
Uncomfortable after hearing about pr e s s release about a v a n d i a . Will switch to actos
Heard about avandia concerns Discontinue avandia
I do not want to be on avandia any longer Patient switched to actos
There is no documented patient concern and the rosiglitazone is discontinued
Had discussion with cardiologist who recomm ended change from avandia to actos given history of MI
Discontinued avandia; patient declined takin g it; th ough risk vs benefit explained to her.
Because of issues related to avandia; will switch to actos.
Discussed changing avandia to actos
The patient has been taken off avandia because of public n otices that there are issues with this drug.
The patient was recently taken off Avandia b e c a use of some concerns in the public media.
She stopped her avandia because she heard of possible cardiac risks.
Concerned about avandia; will discontinue
Would like to stop avandia and go on another medication; changed to actos
opyright © 2011 SciRes. PP
The Impact of a Drug Safety Warning on Discussions Between Doctors and Their Patients; the Case of Rosiglitazone 171
article. For the 40.7 percent who were switched to an-
other medication, the most common theme abstracted
from the comments was that the patient was concerned
about the reports and preferred to make the change.
The timeframe of response and decline in use of rosig-
litazone in this study is similar to that reported in studies
of other medications after reports of concerning adverse
side effects. Previous work on reports of adverse events
related to calcium channel blockers in the setting of
myocardial infarction demonstrated a 20 percent reduc-
tion of the use of this class of medications within months
of the published report . A similarly rapid, but larger
reduction (66 percent) in the use of Prempro was noted
over a 6-month period after reports of increased risk of
breast cancer and cardiovascular disease were linked
with estrogen/progestin combination therapy .
Another important finding from this study is how phy-
sicians’ perceive a drug side effect as being unique to the
drug and not class specific. The majority of patients who
were changed to another medication were placed on
pioglitazone. Given this information, it seems likely that
many providers felt that this is not a class effect. This
finding is supported by a recent study by Cohen and as-
sociates . They found that while rosiglitazone use de-
clined sharply from 0.42 million monthly treatment visits
(February 2007) to 0.13 million monthly treatment visits
(May 2008); pioglitazone use remained stable. Given
that the FDA adviso ry was “class-level” for these agen ts,
it is unclear how physicians ca me to make the distinction
between rosigl it azone a n d pi o gl it azone.
Following the patients over a 2-year period demon-
strated that there was little change over time for those
who were advised to continue rosiglitazone. However,
there were few new starts of rosiglitazone. Only 4 pa-
tients on the registry were started on this drug during the
two-year period observation period; from June 14, 2007
through June 14, 2009. Again, this is consistent with the
findings of Cohen and associates .
This study has a number of limitations. The informa-
tion was abstracted from the medical records and relied
on documentation. It is likely that this led to underre-
porting of discussions between doctors and their patients.
This study cannot reliably determine the source of in-
formation which led to the discussion. Some of the ab-
stracted comments attributed to patients’ suggest that
concerns solely came from the newsmedia; however,
there may have been other sources that prompted patients
to express their concerns; e.g. family members, pharma-
cists, and the internet. This study cannot determine the
extent of concern exhibited by the patient to the provider
and the extent to which that influenced the physician’s
response. Further, there may have been other characteris-
tics of patients such as age, gender, ethnicity, socioeco-
nomic status, level of diabetes control, and prior treat-
ments which could have influenced the physician’s re-
sponse to these concerns. Length of use may also play a
role. Patients on rosiglitazone for longer periods of time
with no adverse side effects may perceive their risk for
harm differently. This response was described by Faber
and associates in their study on the influence of studies
on harm associated with HRT . Specifically, long-
term HRT users were less likely to discontinue their
medication. This study could not determine the role of
style differences among physicians in the outcome of this
study. While all providers were primary care physicians;
i.e. family physicians and general internists; it is likely
that these physicians view risk and assess the literatu re in
a different manner or are more strongly influenced by
other sources; e.g. opinions of colleagues, specialists, or
pharmaceutical representatives. Again, this study could
not determine how the decision was finally made. It ap-
pears that many patient concerns were met with recom-
mendations to continue the drug.
This study also provides important lessons learned for
future research on the practice effects when faced with
the report of potential harm. There is a need for more
research on the factors which influence decision-making
and the role of the patient in this process. For example,
the documented comments suggest that patients were the
ones who initiated the discussion about adverse side ef-
fects with their providers in many of these cases. How-
ever, the majority of patients remained on rosiglitazone.
This finding is somewhat contrary to the findings of prior
research on how patients influence physicians. Kravitz
and associates demonstrated that patients may have a
substantial influence on physicians prescribing behavior
. In this community-based randomized trail, antide-
pressants were prescribed far more often when standard-
ized patients requested them. This might potentially
mean that there is a different perception among physi-
cians in starting versus discontinuing a medication.
Future research should also consider the influence of
the media; including the journal source. High impact
journals are perceived as having more influence on pro-
viders. While the impact factor was not intended to be a
marker for likelihood of practice change, this study
brings into focus the question of what sources a physi-
cian trusts when concerns for harm are reported and
warrants further investigation . The expansion in use
of social media Web sites, the credibility of this informa-
tion, and how it may influence doctor/patient discussions
also warrants further investigat i on.
Finally, future research should assess the influence of
consensus statements by specialty organizations and
warnings by the Food and Drug Administration (FDA).
For example, despite statements from the American Di-
Copyright © 2011 SciRes. PP
172 The Impact of a Drug Safety Warning on Discussions Between Doctors and Their Patients; the Case of Rosiglitazone
abetes Association and the European Association for the
Study of Diabetes recommending against the drug’s use,
data showed that use persisted . After the FDA
boxed warning was issued, there remained substantial
use of rosiglitazone in certain geographic areas of this
In conclusion, the majority of physicians in this study
continued to prescribe rosiglitazone after a highly publi-
cized report demonstrated possible harm from the drug.
Physician’s documented comments suggest that they
either: wanted more data before determining if the drug
was not safe or discounted the validity of the safety con-
cerns. Further research into the factors that influence
patients and physician’s when a report of harm is pub-
lished is warranted.
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