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   <front>
      <journal-meta>
         <journal-id journal-id-type="nlm-ta">PLoS Med</journal-id>
         <journal-id journal-id-type="publisher-id">pmed</journal-id>
         <journal-title>PLoS Medicine</journal-title>
         <issn pub-type="ppub">1549-1277</issn>
         <issn pub-type="epub">1549-1676</issn>
         <publisher>
            <publisher-name>Public Library of Science</publisher-name>
            <publisher-loc>San Francisco, USA</publisher-loc>
         </publisher>
      </journal-meta>
      <article-meta>
         <article-id pub-id-type="doi">10.1371/journal.pmed.0030198</article-id>
         <article-categories>
            <subj-group subj-group-type="heading">
               <subject>Policy Forum</subject>
            </subj-group>
            <subj-group subj-group-type="Discipline">
               <subject>Other</subject>
               <subject>Pharmacology/Drug Discovery</subject>
               <subject>Epidemiology/Public Health</subject>
               <subject>Health Policy</subject>
            </subj-group>
            <subj-group subj-group-type="System Taxonomy">
               <subject>Regulation</subject>
               <subject>Drugs and Adverse Drug Reactions</subject>
               <subject>Public Health</subject>
               <subject>Health Education (Including Prevention and Promotion)</subject>
               <subject>Patients</subject>
            </subj-group>
         </article-categories>
         <title-group>
            <article-title>Disease Mongering in Drug Promotion: Do Governments Have a Regulatory Role?</article-title>
            <alt-title alt-title-type="running-head">Policy Forum</alt-title>
         </title-group>
         <contrib-group>
            <contrib contrib-type="author">
               <name>
                  <surname>Mintzes</surname>
                  <given-names>Barbara</given-names>
               </name>
            </contrib>
         </contrib-group>
         <author-notes>
            <fn fn-type="conflict" id="n1">
               <p>
                  <bold>Competing Interests:</bold> The author has declared that no competing interests exist. </p>
            </fn>
            <fn fn-type="current-aff" id="n2">
               <p>Barbara Mintzes is part of the Therapeutics Initiative, Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia,
                  Canada. E-mail: <email>bmintzes&#x00040;chspr.ubc.ca</email>
               </p>
            </fn>
         </author-notes>
         <pub-date pub-type="ppub">
            <month>4</month>
            <year>2006</year>
         </pub-date>
         <pub-date pub-type="epub">
            <day>11</day>
            <month>04</month>
            <year>2006</year>
         </pub-date>
         <volume>3</volume>
         <issue>4</issue>
         <elocation-id>e198</elocation-id>
         <copyright-statement>Copyright: &#x000a9; 2006 Barbara Mintzes. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
            unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
         <copyright-year>2006</copyright-year>
         <abstract abstract-type="toc">
            <p>Most regulatory agencies, says Mintzes, fail to treat regulation of drug promotion as a public health concern. Unless this changes, she says, the public can expect more unfettered
               disease mongering.</p>
         </abstract>
      </article-meta>
   </front>
   <body>
      <disp-formula id="pmed-0030198-e001">
         <graphic mimetype="image" position="float" xlink:href="pmed.0030198.e001.jpg"/>
      </disp-formula>
      <p>Ray Moynihan and colleagues describe disease mongering as, &#x0201c;widening the boundaries of treatable illness in order to expand markets for those who sell and deliver
         treatments&#x0201d; &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b1">1</xref>&#x0005d;. In this article, I examine one aspect of disease mongering: activities financed by
         drug companies to promote sales by expanding the pool of patients potentially treated by their products, when no benefit in terms of reduced morbidity is likely. New diseases may be
         &#x0201c;created&#x0201d; or existing conditions redefined. In theory, these activities are covered by national laws governing drug promotion that forbid misleading or deceptive
         advertising. However, enforcement is piecemeal and largely ineffective. </p>
      <p>Drug regulation remains limited in many parts of the world. In 2004, fewer than one-sixth of countries had a well-developed system of drug regulation, and one-third had little to no
         regulatory capacity &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b2">2</xref>&#x0005d;. Although 89 countries (46&#x00025;) reported active regulation of drug promotion,
         resources devoted to this work may be limited &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b3">3</xref>&#x0005d;. </p>
      <p>Full direct-to-consumer advertising (DTCA) of prescription drugs is legal in only the United States and New Zealand. However, in many other countries, unbranded disease-oriented advertising
         (in which no drug names are mentioned, but patients are often advised to &#x0201c;see your doctor&#x0201d;) is increasingly common. The Dutch Health-Care Inspectorate reviewed 28
         product-specific marketing plans for prescription drugs, from ten companies, obtained through subpoenas from 1999 to 2002; 3.5&#x00025; of their budgets were devoted to DTCA &#x0005b;
            <xref ref-type="bibr" rid="pmed-0030198-b4">4</xref>&#x0005d;. A market analyst reports that drug companies spent US&#x00024;85 million on unbranded DTCA in Europe in 2004
         &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b5">5</xref>&#x0005d;. Spending is expected to reach US&#x00024;345.5 million by 2008. In 2005, the Australia&#x02013;US free
         trade agreement allowed unbranded advertising in Australian media to be linked to branded information on Web sites &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b6"
         >6</xref>&#x0005d;. Canada introduced more lenient policies on unbranded advertising in 1996, a shift that has occurred without legislative change &#x0005b; <xref ref-type="bibr"
            rid="pmed-0030198-b7">7</xref>&#x0005d;. </p>
      <p>A claimed benefit of disease-awareness campaigns is that the public becomes more aware of untreated health problems and seeks effective care at an earlier stage, leading to better health
         &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b8">8</xref>&#x0005d;. For this to happen, the campaigns must address important health concerns, focus on patients likely to benefit
         from diagnosis and treatment, and steer them towards appropriate care. For the individual patient, drug treatment is worth pursuing if potential benefits outweigh potential harm. But as
         healthier people are targeted, the added benefit of drug treatment can become increasingly elusive. </p>
      <sec id="s2">
         <title>Limited Regulatory Oversight of Unbranded Disease-Awareness Adverts</title>
         <p>The US Food and Drug Administration (FDA) published a guidance in 2004 stating that unbranded adverts that are perceptually similar or otherwise linked to branded adverts are subject to
            FDA regulation, as are unbranded adverts by the manufacturer of the only drug in its class &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b9">9</xref>&#x0005d;. Otherwise, the
            FDA has no authority over the content of disease-oriented advertising, although it recommends responsible public health messages. The United Kingdom Medicines Health-Care Products
            Regulatory Agency has issued guidelines stating that the primary purpose of disease-awareness advertising must be health education on a disease and its management, not product promotion
            &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b10">10</xref>&#x0005d;. However, the Medicines Health-Care Products Regulatory Agency allowed Novartis' advertising on fungal
            nail infections (onychomycosis), which stressed high prevalence and infectiousness and guided viewers to prescription drugs, including Novartis' drug terbinafine (Lamisil) &#x0005b;
               <xref ref-type="bibr" rid="pmed-0030198-b10">10</xref>&#x0005d;. </p>
         <p>In the Netherlands, a similar Novartis campaign for onychomycosis prompted the Dutch government to take Novartis to court for illegal DTCA. The government lost the case as neither the
            product nor the manufacturer was named &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b11">11</xref>&#x0005d;. &#x02018;t Jong and colleagues subsequently analyzed the
            effects of the campaign on primary care, using administrative data covering 150 practices. They studied the changes in rates of prescriptions of oral terbinafine (Lamisil) and itraconazole
            (Sporanox, a competitor to Lamisil), and the onychomycosis consultation rate, before and after the start of the campaign. Both onychomycosis consultations and prescriptions for terbinafine
            (Lamisil) grew, whereas prescriptions for the competitor drug declined &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b12">12</xref>&#x0005d;. Thus, an unbranded campaign had a
            brand-specific effect on sales, most likely because of concurrent branded promotion to physicians. &#x02018;t Jong et al. noted the effects of promotion of a condition that is largely
            cosmetic (it usually causes no pain or suffering) on physicians' workload. </p>
      </sec>
      <sec id="s3">
         <title>Promoting Sales through Fear of Death</title>
         <p>Pfizer, the manufacturer of Lipitor (atorvastatin), ran a campaign in France and Canada in 2003 with print adverts that used images of a tagged toe of a corpse (the Canadian campaign was
            in association with the Canadian Lipid Nurse Network and the Canadian Diabetes Association) ( <xref ref-type="fig" rid="pmed-0030198-g001">Figure 1</xref>). On television, a youthful,
            healthy man died suddenly of a heart attack, leaving his family devastated with grief. The message of these two adverts was that cholesterol testing and treatment could prevent premature
            death from heart attacks in healthy people. This was at odds with existing scientific evidence: a 2003 meta-analysis of cholesterol-lowering drugs in primary prevention found no difference
            in mortality between drug and placebo &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b13">13</xref>&#x0005d;. </p>
         <p>Jonathan Quick and colleagues at the World Health Organization raised concerns in the <italic>Lancet</italic> that the adverts misinformed the public about cardiovascular risks and could
            lead to harm from medically unjustified drug use &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b14">14</xref>&#x0005d;. They argued that governments should take a more active
            role in regulating disease-awareness campaigns to prevent misleading information from reaching the public. Complaints in Canada, which included the <italic>Lancet</italic> letter, resulted
            in no regulatory action &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b15">15</xref>&#x0005d;. A subsequent advert shows a man walking down a city street, unaware that he is
            about to be charged by a rhinoceros. The tagline is the following: &#x0201c;Living with high cholesterol, you never know what's around the corner.&#x0201d; The text stresses the
            risk of death from heart attacks. The only risk factor discussed is cholesterol. </p>
         <p>Disease-awareness advertising is often the visible face of broader commercial influences. Eight of the nine authors of the US cholesterol treatment guidelines released in 2004 had
            financial links to manufacturers (Cleeman was the only member of the panel with no such ties; see <ext-link ext-link-type="uri"
               xlink:href="http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm">http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04_disclose.htm</ext-link>) &#x0005b;
               <xref ref-type="bibr" rid="pmed-0030198-b16">16</xref>&#x0005d;. These guidelines extended treatment of high cholesterol to patient groups in which a morbidity and mortality
            advantage had not been established. A Pfizer financial report on atorvastatin (Lipitor) states, &#x0201c;There continues to be an opportunity for further growth of the
            cholesterol-lowering market&#x02026;.Evolving treatment guidelines continue to encourage the broad use of statin therapy&#x0201d; &#x0005b; <xref ref-type="bibr"
               rid="pmed-0030198-b17">17</xref>&#x0005d;. </p>
      </sec>
      <sec id="s4">
         <title>Hormone Replacement Therapy and Menopause: An Ongoing Saga</title>
         <p>Promotion of hormone replacement therapy (HRT) for disease prevention is a key example of disease mongering linked to drug sales. Women learned to view menopause in terms of increased
            health risks that could be prevented with HRT. The first long-term randomized controlled trial of HRT in healthy women, the Women's Health Initiative, found a 1&#x00025; increase in
            absolute risks for serious harm over five years, mainly due to cardiovascular adverse effects &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b18">18</xref>&#x0005d;. The
            negative public health impact of HRT use by millions of women worldwide is likely to have been considerable. Regulatory agencies have changed labelling to warn potential users of serious
            risks and to advise limiting use to short-term symptomatic treatment, but have taken no broader action to review marketing of drugs for disease prevention. </p>
         <p>On 28 December 2005, the first hit on a Google search on &#x0201c;menopause and estrogen deficiency&#x0201d; was a Merck Web site promoting an estrogen patch, and linking
            postmenopausal estrogen deficiency to reduced performance, fine motor skills, memory, and a reduction in &#x0201c;planned, targeted, flexible and adaptable thought&#x0201d;
            &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b19">19</xref>&#x0005d;. </p>
         <p>In 2006, a handbook for journalists, called <italic>The Journalist's Menopause Handbook</italic>, which was funded by Wyeth Canada and produced by a medical society (the Society of
            Obstetricians and Gynaecologists of Canada), fails to mention increased risks of strokes, heart attacks, pulmonary emboli, or symptoms of probable dementia associated with HRT
            &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b20">20</xref>&#x0005d;. The magnitude of breast cancer risk is described as no greater than lifestyle-associated risks. Hot
            flushes, mood and memory, appearance (wrinkles), sleep disturbances, bladder control, and sexual changes are listed as menopausal symptoms. Short-term HRT for moderate to severe symptoms
            is recommended as safe and effective, with &#x0201c;short-term&#x0201d; defined as up to five years &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b20"
            >20</xref>&#x0005d;. Beyond the lack of established link between wrinkles and menopause (rather than ageing per se), is HRT really a reasonable treatment for wrinkles, given the
            cardiovascular, cancer, and dementia risks? </p>
      </sec>
      <sec id="s5">
         <title>Lower Thresholds for Symptomatic Treatment and Public Health</title>
         <p>Mamdani and colleagues found that following the launch of celecoxib (Celebrex) and rofecoxib (Vioxx), more elderly patients in Ontario were treated with nonsteroidal anti-inflammatory
            drugs (NSAIDs) than previously &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b21">21</xref>&#x0005d;. The increase was attributable to use of Cox-2 inhibitors by people not
            previously taking NSAIDs. Paradoxically, although these newer drugs were promoted for greater gastrointestinal safety, Mamdani and colleagues found that approximately 650 more
            hospitalizations for gastrointestinal bleeds occurred per year after the drugs' introduction. In their conclusion, the authors stated the following: &#x0201c;Although we cannot prove
            causation, we believe that the striking temporal correlation, biological plausibility, and lack of any other trends that would explain the association strongly suggest that the two events
            are directly related&#x0201d; &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b21">21</xref>&#x0005d;. </p>
         <p>Another heavily promoted class of drugs are the proton pump inhibitors. Bashford and colleagues analyzed why patients were prescribed proton pump inhibitors during a five-year period in
            which prescribing increased 10-fold. By 1995, 46&#x00025; of prescriptions were for off-label uses, mainly milder problems &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b22"
            >22</xref>&#x0005d;. In 2004, researchers found a link between use of proton pump inhibitors and higher risks of <named-content content-type="genus-species">Clostridium
            difficile</named-content> infection in hospitalized patients &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b23">23</xref>&#x0005d;. A US magazine advertisement for esomeprazole
            (Nexium) in November 2005 (e.g., printed in <italic>Family Circle</italic>), a year after this study, warns readers that &#x0201c;something could be brewing&#x0201d; beneath their
            heartburn. A distressed woman is shown with a red scarf around her neck, and on the scarf is the following statement: &#x0201c;Behind this scarf acid could be burning the lining of her
            esophagus.&#x0201d; The advert quotes a high rate of erosive esophagitis among people with acid reflux, one in three, based on data on file at AstraZeneca. Although the advert contains
            the disclaimer that &#x0201c;only a doctor can determine if you have this condition,&#x0201d; the image of distress and the larger headlines&#x02014;such as &#x0201c;Acid
            reflux disease can damage your esophagus&#x0201d; and &#x0201c;Nexium heals the damage&#x0201d;&#x02014;convey the message to be anxious about heartburn and consider it a
            possible sign of more serious disease. Like many US adverts, this one offers a free trial. </p>
      </sec>
      <sec id="s6">
         <title>Questionable New Indications</title>
         <p>Regulatory agencies have differed in their response to manufacturers' bids to market selective serotonin reuptake inhibitor (SSRI) antidepressants for &#x0201c;premenstrual dysphoric
            dysfunction&#x0201d; (PMDD). Business analysts linked the launch of the first drug in the US for this indication, fluoxetine (Sarafem), to Eli Lilly's pending loss of patent protection
            for Prozac (also fluoxetine) &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b24">24</xref>&#x0005d;. </p>
         <p>The European Medicines Evaluation Agency refused to approve drugs for PMDD, raising concerns that women &#x0201c;with less severe pre-menstrual symptoms might erroneously receive a
            diagnosis of PMDD resulting in widespread inappropriate short- and long-term use of fluoxetine&#x0201d; &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b25"
            >25</xref>&#x0005d;. The US and Australia have approved SSRIs for PMDD, but Australia does not cover their costs &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b26"
            >26</xref>&#x0005d;. </p>
         <p>Soon after Sarafem's launch, the FDA judged a TV advert to violate US law because it failed to distinguish clearly between PMDD and premenstrual syndrome &#x0005b; <xref
               ref-type="bibr" rid="pmed-0030198-b27">27</xref>&#x0005d;. A US community survey of women aged 14&#x02013;24 found a 6&#x00025; prevalence of PMDD. An additional
            19&#x00025; were &#x0201c;near-threshold&#x0201d; cases &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b28">28</xref>&#x0005d;. This survey likely overestimated
            PMDD, as classification was based on recall rather than daily symptom diaries (and most women were only mildly impaired), but the high &#x0201c;near-threshold&#x0201d; prevalence
            highlights the profitability of broadening diagnostic boundaries &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b29">29</xref>&#x0005d;. </p>
      </sec>
      <sec id="s7">
         <title>Disease Claims in US DTCA: A Mixed Regulatory Response</title>
         <p>Unlike many countries that rely primarily on industry self-regulation, the FDA regulates prescription drug promotion directly. Letters of violation to manufacturers are posted on the FDA
            Web site, with detailed rationales for regulatory decisions &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b30">30</xref>&#x0005d;. Of the 51 letters sent to companies in 2004
            to mid-December 2005, 21 were either on DTCA exclusively ( <italic>n</italic> &#x0003d; 15) or on both DTCA and promotion for health professionals ( <italic>n</italic> &#x0003d;
            6). For 15 out of 21 (71&#x00025;) letters, reviewers from the FDA's Division of Drug Marketing, Advertising, and Communications raised concerns related to disease mongering ( <xref
               ref-type="table" rid="pmed-0030198-t001">Table 1</xref>). These concerns often consisted of (1) off-label promotion broadening approved indications and (2) misrepresentation of disease
            so as to exaggerate treatment effectiveness. </p>
         <p>Many examples also exist of disease mongering in US DTCA that has not been subject to regulation. In a recent article in <italic>PLoS Medicine</italic>, Lacasse and Leo reviewed the
            evidence supporting the hypothesis that depression is caused by a serotonin deficiency, concluding that a lack of evidence exists to support this hypothesis &#x0005b; <xref
               ref-type="bibr" rid="pmed-0030198-b31">31</xref>&#x0005d;. They questioned the FDA's lack of attention to the claims in SSRI adverts for antidepressants that depression and anxiety
            disorders are caused by a chemical imbalance in the brain. The Irish regulatory agency has prohibited GlaxoSmithKline from making similar claims to support the use of paroxetine (Paxil)
            &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b32">32</xref>&#x0005d;. </p>
         <p>Kravitz and colleagues found more broadly that patient requests for advertised medicines could lead to off-label antidepressant prescribing for &#x0201c;adjustment
            disorder,&#x0201d; a disorder involving temporary distress due to a troubling life situation that rarely requires drug treatment &#x0005b; <xref ref-type="bibr"
               rid="pmed-0030198-b33">33</xref>&#x0005d;. Standardized patients received antidepressant prescriptions just over half the time if they requested the advertised antidepressant Paxil,
            whether they had symptoms of depression or adjustment disorder. If patients had not requested a drug, physicians were much less likely to prescribe antidepressants for adjustment disorder.
            This study provides experimental evidence of a link between patient requests for medicines and unnecessary medicalization. </p>
      </sec>
      <sec id="s8">
         <title>Conclusion: Is a More Robust Regulatory Response Needed?</title>
         <p>
            <xref ref-type="boxed-text" rid="box1">Box 1</xref> summarizes the types of disease-mongering activities companies can use to stimulate drug sales, including those described above. </p>
         <p>The rationale for regulation of drug promotion is health protection, encouragement of appropriate medicine use, and prevention of deceptive advertising. The European community code on
            medicinal products for human use states that advertising of medicinal products &#x0201c;must encourage the rational use of the product and may not be misleading&#x0201d;
            &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b34">34</xref>&#x0005d;. Canada's Food and Drugs Act prohibits advertising of a drug that is &#x0201c;false, misleading or
            deceptive or is likely to create an erroneous impression regarding its character, value, quantity, merit or safety&#x0201d; &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b35"
               >35</xref>&#x0005d;. The World Health Organization's Ethical Criteria for Medicinal Drug Promotion states that advertisements, &#x0201c;&#x02026;should not take undue
            advantage of people's concern for their health&#x0201d; &#x0005b; <xref ref-type="bibr" rid="pmed-0030198-b36">36</xref>&#x0005d;. </p>
         <p>Disease mongering by definition creates erroneous impressions of the condition a product aims to treat and the merit and safety of treatment, and frequently provokes undue anxiety or
            exaggerates prevalence rates. Many of the activities in <xref ref-type="boxed-text" rid="box1">Box 1</xref> are off-label promotions. </p>
         <p>The prohibition of DTCA is consistent with regulatory aims to protect health and encourage appropriate medicine use. Unbranded disease-awareness campaigns for the condition a
            manufacturer's drug aims to treat are a form of DTCA. If these adverts are allowed under laws guaranteeing commercial freedom of expression, a regulatory rationale remains to (1) de-link
            them from suggestions to &#x0201c;ask your doctor&#x0201d; for a treatment and (2) to insist on prescreening of adverts by a government agency to ensure conformity with the law
            before they are broadcast or printed. Similarly, drug company funding of media promotions aiming to stimulate sales should be subject to the same regulatory control as direct advertising.</p>
         <p>Better definitions are needed of the indications drugs are approved to treat, to ensure consistency with assessed outcomes in premarket trials. Evidence of benefit should be based on
            clinical outcomes, and greater caution is needed in introducing new diagnoses.</p>
         <p>A key question is whether there is sufficient political will among government regulatory agencies to better enforce existing regulations governing drug promotion or to introduce new
            solutions. Most regulatory agencies fail to treat regulation of drug promotion as a public health concern. Unless this changes, the public can expect more unfettered disease mongering
            warning them that without the latest treatment, life will be grim indeed.</p>
         <boxed-text id="box1" position="float">
            <sec id="s9">
               <title>Box 1. Forms of Disease Mongering Used to Expand Drug Sales</title>
               <p>
                  <list list-type="bullet">
                     <list-item>
                        <p>Promotion of anxiety about future ill-health in healthy individuals</p>
                     </list-item>
                     <list-item>
                        <p>Inflated disease prevalence rates</p>
                     </list-item>
                     <list-item>
                        <p>Promotion of aggressive drug treatment of milder symptoms and diseases</p>
                     </list-item>
                     <list-item>
                        <p>Introduction of questionable new diagnoses&#x02014;such as PMDD or social anxiety disorder&#x02014;that are hard to distinguish from normal life</p>
                     </list-item>
                     <list-item>
                        <p>Redefinition of diseases in terms of surrogate outcomes (i.e., osteoporosis becomes a disease of low bone density rather than fragility fractures)</p>
                     </list-item>
                     <list-item>
                        <p>Promotion of drugs as a first-line solution for problems previously not considered medical, such as disruptive classroom behaviour or problematic sexual relationships.</p>
                     </list-item>
                  </list>
               </p>
            </sec>
         </boxed-text>
      </sec>
   </body>
   <back>
      <ref-list>
         <title>References</title>
         <ref id="pmed-0030198-b1">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Moynihan</surname>
                     <given-names>R</given-names>
                  </name>
                  <name>
                     <surname>Heath</surname>
                     <given-names>I</given-names>
                  </name>
                  <name>
                     <surname>Henry</surname>
                     <given-names>D</given-names>
                  </name>
               </person-group>
               <article-title>Selling sickness: The pharmaceutical industry and disease mongering</article-title>
               <source>BMJ</source>
               <year>2002</year>
               <volume>324</volume>
               <fpage>886</fpage>
               <lpage>891</lpage>
               <pub-id pub-id-type="pmid">11950740</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b2">
            <citation citation-type="book">
               <collab>World Health Organization</collab>
               <source>World medicines situation</source>
               <year>2004</year>
               <publisher-loc>Geneva</publisher-loc>
               <publisher-name>World Health Organization</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://w3.whosea.org/LinkFiles/Reports_World_Medicines_Situation.pdf"
                     >http://w3.whosea.org/LinkFiles/Reports_World_Medicines_Situation.pdf</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b3">
            <citation citation-type="book">
               <person-group person-group-type="author">
                  <name>
                     <surname>Brown</surname>
                     <given-names>B</given-names>
                  </name>
               </person-group>
               <collab>Standing Committee on Health</collab>
               <source>Opening the medicine cabinet: First report on health aspects of prescription drugs</source>
               <year>2004</year>
               <publisher-loc>Ottawa (Ontario)</publisher-loc>
               <publisher-name>House of Commons</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.parl.gc.ca/InfocomDoc/Documents/37/3/parlbus/commbus/house/reports/healrp01-e.htm"
                     >http://www.parl.gc.ca/InfocomDoc/Documents/37/3/parlbus/commbus/house/reports/healrp01-e.htm</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b4">
            <citation citation-type="book">
               <person-group person-group-type="author">
                  <name>
                     <surname>Van Egmond-Vettenburg</surname>
                     <given-names>JS</given-names>
                  </name>
                  <name>
                     <surname>ter Steege</surname>
                     <given-names>H</given-names>
                  </name>
               </person-group>
               <source>Marketing plans for medicinal products available on prescription only: The current situation. Health Care Inspectorate</source>
               <year>2001</year>
               <publisher-loc>Amsterdam</publisher-loc>
               <publisher-name>The Hague</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://healthyskepticism.org/publications/editions/2002/IN04.htm"
                     >http://healthyskepticism.org/publications/editions/2002/IN04.htm</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b5">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Parmar</surname>
                     <given-names>H</given-names>
                  </name>
               </person-group>
               <article-title>The communication gap: Pharmaceutical direct-to-consumer advertising in Europe</article-title>
               <source>Pharmaceutical Field</source>
               <year>2005</year>
               <month>12</month>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.inpharm.com/static/intelligence/pdf/MAG_394184.pdf"
                     >http://www.inpharm.com/static/intelligence/pdf/MAG_394184.pdf</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b6">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Outterson</surname>
                     <given-names>K</given-names>
                  </name>
               </person-group>
               <article-title>Agony in the antipodes: The generic drug provisions of the Australia&#x02013;USA free trade agreement</article-title>
               <source>J Gen Med</source>
               <year>2005</year>
               <volume>2</volume>
               <fpage>316</fpage>
               <lpage>326</lpage>
            </citation>
         </ref>
         <ref id="pmed-0030198-b7">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Gardner</surname>
                     <given-names>D</given-names>
                  </name>
                  <name>
                     <surname>Mintzes</surname>
                     <given-names>B</given-names>
                  </name>
                  <name>
                     <surname>Ostry</surname>
                     <given-names>A</given-names>
                  </name>
               </person-group>
               <article-title>Direct-to-consumer prescription drug advertising in Canada: Permission by default?</article-title>
               <source>CMAJ</source>
               <year>2003</year>
               <volume>169</volume>
               <fpage>425</fpage>
               <lpage>427</lpage>
               <pub-id pub-id-type="pmid">12952804</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b8">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Berndt</surname>
                     <given-names>ER</given-names>
                  </name>
               </person-group>
               <article-title>To inform or persuade? Direct-to-consumer advertising of prescription drugs</article-title>
               <source>N Engl J Med</source>
               <year>2005</year>
               <volume>352</volume>
               <fpage>325</fpage>
               <lpage>328</lpage>
               <pub-id pub-id-type="pmid">15673797</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b9">
            <citation citation-type="book">
               <collab>Division of. Drug Marketing Advertising and Communication US Food and Drug Administration</collab>
               <article-title>Guidance for industry</article-title>
               <source>&#x0201c;Help-seeking&#x0201d; and other disease awareness communications by or on behalf of drug and device firms</source>
               <year>2004</year>
               <publisher-loc>Rockville (Maryland)</publisher-loc>
               <publisher-name>US Food and Drug Administration</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/cder/guidance/6019dft.pdf">http://www.fda.gov/cder/guidance/6019dft.pdf</ext-link>. Accessed 7 March
                  2006</comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b10">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Jackson</surname>
                     <given-names>T</given-names>
                  </name>
               </person-group>
               <article-title>Regulator spells out rules on disease awareness campaigns</article-title>
               <source>BMJ</source>
               <year>2003</year>
               <volume>326</volume>
               <fpage>1219</fpage>
            </citation>
         </ref>
         <ref id="pmed-0030198-b11">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Sheldon</surname>
                     <given-names>T</given-names>
                  </name>
               </person-group>
               <article-title>Dutch GPs call for a ban on Novartis products</article-title>
               <source>BMJ</source>
               <year>2002</year>
               <volume>325</volume>
               <fpage>355</fpage>
               <pub-id pub-id-type="pmid">12183299</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b12">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>&#x02018;tJong</surname>
                     <given-names>GW</given-names>
                  </name>
                  <name>
                     <surname>Stricker</surname>
                     <given-names>BWH</given-names>
                  </name>
                  <name>
                     <surname>Sturkenboom</surname>
                     <given-names>MCJM</given-names>
                  </name>
               </person-group>
               <article-title>Marketing in the lay media and prescriptions of terbinafine in primary care</article-title>
               <source>BMJ</source>
               <year>2004</year>
               <volume>328</volume>
               <fpage>931</fpage>
               <pub-id pub-id-type="pmid">14988148</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b13">
            <citation citation-type="journal">
               <collab>Therapeutics Initiative</collab>
               <article-title>Do statins have a role in primary prevention? Ther Lett 48</article-title>
               <year>2003</year>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.ti.ubc.ca/PDF/48.pdf">http://www.ti.ubc.ca/PDF/48.pdf</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b14">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Quick</surname>
                     <given-names>JD</given-names>
                  </name>
                  <name>
                     <surname>Hogerzeil</surname>
                     <given-names>HV</given-names>
                  </name>
                  <name>
                     <surname>Rago</surname>
                     <given-names>L</given-names>
                  </name>
                  <name>
                     <surname>Reggi</surname>
                     <given-names>V</given-names>
                  </name>
                  <name>
                     <surname>de Joncheere</surname>
                     <given-names>K</given-names>
                  </name>
               </person-group>
               <article-title>Ensuring ethical drug promotion&#x02014;Whose responsibility?</article-title>
               <source>Lancet</source>
               <year>2003</year>
               <volume>362</volume>
               <fpage>747</fpage>
               <pub-id pub-id-type="pmid">12957107</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b15">
            <citation citation-type="book">
               <person-group person-group-type="author">
                  <name>
                     <surname>Pettigrew</surname>
                     <given-names>P</given-names>
                  </name>
               </person-group>
               <article-title>Letter to Anne Rochon Ford</article-title>
               <source>Minister of health</source>
               <year>2005</year>
               <publisher-loc>Toronto (Ontario)</publisher-loc>
               <publisher-name>Women and Health Protection</publisher-name>
               <comment>June 16, 2004. Available: <ext-link ext-link-type="uri" xlink:href="http://www.whp-apsf.ca/pdf/Pfizer_adRresponse.pdf"
                  >http://www.whp-apsf.ca/pdf/Pfizer_adRresponse.pdf</ext-link>. Accessed 7 March 2006</comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b16">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Lenzer</surname>
                     <given-names>J</given-names>
                  </name>
               </person-group>
               <article-title>US consumer body calls for review of cholesterol guidelines</article-title>
               <source>BMJ</source>
               <year>2004</year>
               <volume>329</volume>
               <fpage>759</fpage>
               <pub-id pub-id-type="pmid">15459035</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b17">
            <citation citation-type="book">
               <collab>Pfizer</collab>
               <article-title>Item 2. Management's discussion and analysis of financial condition and results of operations</article-title>
               <source>Form 10-Q for Pfizer Inc</source>
               <year>2006</year>
               <month>5</month>
               <day>6</day>
               <publisher-loc>New York</publisher-loc>
               <publisher-name>Pfizer</publisher-name>
               <comment>Quarterly report. Available: <ext-link ext-link-type="uri" xlink:href="http://biz.yahoo.com/e/050506/pfe10-q.html">http://biz.yahoo.com/e/050506/pfe10-q.html</ext-link>.
                  Accessed 7 March 2006</comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b18">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Rossouw</surname>
                     <given-names>JE</given-names>
                  </name>
                  <name>
                     <surname>Anderson</surname>
                     <given-names>GL</given-names>
                  </name>
                  <name>
                     <surname>Prentice</surname>
                     <given-names>RL</given-names>
                  </name>
                  <name>
                     <surname>LaCroix</surname>
                     <given-names>AZ</given-names>
                  </name>
                  <name>
                     <surname>Kooperberg</surname>
                     <given-names>C</given-names>
                  </name>
                  <etal/>
               </person-group>
               <article-title>Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial</article-title>
               <source>JAMA</source>
               <year>2002</year>
               <volume>288</volume>
               <fpage>321</fpage>
               <lpage>333</lpage>
               <pub-id pub-id-type="pmid">12117397</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b19">
            <citation citation-type="book">
               <collab>Fem</collab>
               <source>Menopausal complaints&#x02014;Estrogen deficiency</source>
               <publisher-loc>Darmstadt (Germany)</publisher-loc>
               <publisher-name>Merck KGaA</publisher-name>
               <comment>7 (1998&#x02013;1999)</comment>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.fem7.com/estrogen.htm">http://www.fem7.com/estrogen.htm</ext-link>. Accessed 7 March 2007 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b20">
            <citation citation-type="book">
               <collab>The Society of Obstetricians and Gynaecologists of Canada</collab>
               <source>The journalist's menopause handbook</source>
               <year>2006</year>
               <publisher-loc>Ottawa (Ontario)</publisher-loc>
               <publisher-name>The Society of Obstetricians and Gynaecologists of Canada</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.sogc.org/media/pdf/advisories/Menopause-journalists-guide_e.pdf"
                     >http://www.sogc.org/media/pdf/advisories/Menopause-journalists-guide_e.pdf</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b21">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Mamdani</surname>
                     <given-names>M</given-names>
                  </name>
                  <name>
                     <surname>Juurlink</surname>
                     <given-names>DN</given-names>
                  </name>
                  <name>
                     <surname>Kopp</surname>
                     <given-names>A</given-names>
                  </name>
                  <name>
                     <surname>Naglie</surname>
                     <given-names>G</given-names>
                  </name>
                  <name>
                     <surname>Austin</surname>
                     <given-names>PC</given-names>
                  </name>
                  <etal/>
               </person-group>
               <article-title>Gastrointestinal bleeding after the introduction of Cox-2 inhibitors: Ecological study</article-title>
               <source>BMJ</source>
               <year>2004</year>
               <volume>328</volume>
               <fpage>1415</fpage>
               <lpage>1416</lpage>
               <pub-id pub-id-type="pmid">15138157</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b22">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Bashford</surname>
                     <given-names>JNR</given-names>
                  </name>
                  <name>
                     <surname>Norwood</surname>
                     <given-names>J</given-names>
                  </name>
                  <name>
                     <surname>Chapman</surname>
                     <given-names>SR</given-names>
                  </name>
               </person-group>
               <article-title>Why are patients prescribed proton pump inhibitors? Retrospective analysis of link between morbidity and prescribing in the General Practice Research Database</article-title>
               <source>BMJ</source>
               <year>1998</year>
               <volume>317</volume>
               <fpage>452</fpage>
               <lpage>456</lpage>
               <pub-id pub-id-type="pmid">9703528</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b23">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Dial</surname>
                     <given-names>S</given-names>
                  </name>
                  <name>
                     <surname>Alrasadi</surname>
                     <given-names>K</given-names>
                  </name>
                  <name>
                     <surname>Manoukian</surname>
                     <given-names>C</given-names>
                  </name>
                  <name>
                     <surname>Huang</surname>
                     <given-names>A</given-names>
                  </name>
                  <name>
                     <surname>Menzies</surname>
                     <given-names>D</given-names>
                  </name>
               </person-group>
               <article-title>Risk of <named-content content-type="genus-species">clostridium difficile</named-content> among hospital inpatients prescribed proton pump inhibitors: Cohort and
                  case-control studies </article-title>
               <source>CMAJ</source>
               <year>2004</year>
               <volume>171</volume>
               <fpage>33</fpage>
               <lpage>38</lpage>
               <pub-id pub-id-type="pmid">15238493</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b24">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Class</surname>
                     <given-names>S</given-names>
                  </name>
               </person-group>
               <article-title>Pharma overview</article-title>
               <source>Chem Eng News</source>
               <year>2002</year>
               <volume>80</volume>
               <fpage>39</fpage>
               <lpage>49</lpage>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://pubs.acs.org/cen/coverstory/8048/8048pharmaceutical.html"
                     >http://pubs.acs.org/cen/coverstory/8048/8048pharmaceutical.html</ext-link>. Accessed 7 March 2006</comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b25">
            <citation citation-type="book">
               <collab>European Agency for the Evaluation of Medicinal Products &#x0005b;EMEA&#x0005d;, Committee for Proprietary Medicinal Products &#x0005b;CPMP&#x0005d;</collab>
               <source>Summary information on referral opinion following arbitration pursuant to article 30 of council directive 2001/83/EC for Prozac and associated names</source>
               <year>2003</year>
               <publisher-loc>London</publisher-loc>
               <publisher-name>EMEA</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.emea.eu.int/pdfs/human/referral/326303en.pdf"
                  >http://www.emea.eu.int/pdfs/human/referral/326303en.pdf</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b26">
            <citation citation-type="book">
               <collab>National Prescribing Service</collab>
               <source>Sertraline (Zoloft), fluoxetine (Lovan, Prozac) for premenstrual dysphoric disorder</source>
               <year>2004</year>
               <publisher-loc>Surry Hills (New South Wales)</publisher-loc>
               <publisher-name>National Prescribing Service</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.npsradar.org.au/site.php?page=1&#x00026;content=/npsradar/content/sertraline.html#Reason_for_PBS_listing"
                     >http://www.npsradar.org.au/site.php?page=1&#x00026;content=/npsradar/content/sertraline.html#Reason_for_PBS_listing</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b27">
            <citation citation-type="book">
               <person-group person-group-type="author">
                  <name>
                     <surname>Stockbridge</surname>
                     <given-names>LL</given-names>
                  </name>
               </person-group>
               <source>Untitled letter to G Brophy, Director U.S. Regulatory Affairs, Eli Lilly</source>
               <year>2002</year>
               <publisher-loc>Rockville (Maryland)</publisher-loc>
               <publisher-name>US Food and Drug Administration</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/cder/warn/nov2000/dd9523.pdf">http://www.fda.gov/cder/warn/nov2000/dd9523.pdf</ext-link>. Accessed 7
                  March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b28">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Wittchen</surname>
                     <given-names>HU</given-names>
                  </name>
                  <name>
                     <surname>Becker</surname>
                     <given-names>E</given-names>
                  </name>
                  <name>
                     <surname>Lieb</surname>
                     <given-names>R</given-names>
                  </name>
                  <name>
                     <surname>Krause</surname>
                     <given-names>P</given-names>
                  </name>
               </person-group>
               <article-title>Prevalence, incidence and stability of premenstrual dysphoric disorder in the community</article-title>
               <source>Psychol Med</source>
               <year>2002</year>
               <volume>32</volume>
               <fpage>119</fpage>
               <lpage>132</lpage>
               <pub-id pub-id-type="pmid">11883723</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b29">
            <citation citation-type="book">
               <person-group person-group-type="author">
                  <name>
                     <surname>Moynihan</surname>
                     <given-names>R</given-names>
                  </name>
                  <name>
                     <surname>Cassels</surname>
                     <given-names>A</given-names>
                  </name>
               </person-group>
               <source>Selling sickness: How the worlds biggest pharmaceutical companies are turning us all into patients</source>
               <year>2005</year>
               <publisher-loc>New York</publisher-loc>
               <publisher-name>Nation Books</publisher-name>
               <lpage>254</lpage>
            </citation>
         </ref>
         <ref id="pmed-0030198-b30">
            <citation citation-type="book">
               <collab>US Food and Drug Administration</collab>
               <source>Warning letters and untitled letters to pharmaceutical companies</source>
               <year>2005</year>
               <publisher-loc>Rockville (Maryland)</publisher-loc>
               <publisher-name>US Food and Drug Administration</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://www.fda.gov/cder/warn">http://www.fda.gov/cder/warn</ext-link>. Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b31">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Lacasse</surname>
                     <given-names>J</given-names>
                  </name>
                  <name>
                     <surname>Leo</surname>
                     <given-names>J</given-names>
                  </name>
               </person-group>
               <article-title>Serotonin and depression: A disconnect between the advertisements and the scientific literature</article-title>
               <source>PLoS Med</source>
               <year>2005</year>
               <volume>2</volume>
               <fpage>e392</fpage>
               <pub-id pub-id-type="doi">10.1371/journal.pmed.0020392</pub-id>
               <pub-id pub-id-type="pmid">16268734</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b32">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>O'Brien</surname>
                     <given-names>C</given-names>
                  </name>
               </person-group>
               <article-title>Drug firm to drop non-addiction claim</article-title>
               <source>Irish Times</source>
               <year>2003</year>
               <month>10</month>
               <day>5</day>
            </citation>
         </ref>
         <ref id="pmed-0030198-b33">
            <citation citation-type="journal">
               <person-group person-group-type="author">
                  <name>
                     <surname>Kravitz</surname>
                     <given-names>RL</given-names>
                  </name>
                  <name>
                     <surname>Epstein</surname>
                     <given-names>RM</given-names>
                  </name>
                  <name>
                     <surname>Feldman</surname>
                     <given-names>MD</given-names>
                  </name>
                  <name>
                     <surname>Franz</surname>
                     <given-names>CE</given-names>
                  </name>
                  <name>
                     <surname>Azari</surname>
                     <given-names>R</given-names>
                  </name>
                  <etal/>
               </person-group>
               <article-title>Influence of patients' requests for direct-to-consumer advertised antidepressants: A randomised controlled trial</article-title>
               <source>JAMA</source>
               <year>2005</year>
               <volume>293</volume>
               <fpage>1995</fpage>
               <lpage>2002</lpage>
               <pub-id pub-id-type="pmid">15855433</pub-id>
            </citation>
         </ref>
         <ref id="pmed-0030198-b34">
            <citation citation-type="book">
               <collab>European Commission</collab>
               <source>Community code relating to medicinal products for human use</source>
               <year>2003</year>
               <publisher-loc>Brussels</publisher-loc>
               <publisher-name>European Commission</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://europa.eu.int/scadplus/leg/en/lvb/l21230.htm">http://europa.eu.int/scadplus/leg/en/lvb/l21230.htm</ext-link>.
                  Accessed 7 March 2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b35">
            <citation citation-type="book">
               <collab>Department of Justice &#x0005b;Canada&#x0005d;. Food and Drugs Act</collab>
               <source>Chapter F-27</source>
               <publisher-loc>Ottawa (Ontario)</publisher-loc>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://laws.justice.gc.ca/en/F-27/191368.html">http://laws.justice.gc.ca/en/F-27/191368.html</ext-link>. Accessed 7 March
                  2006 </comment>
            </citation>
         </ref>
         <ref id="pmed-0030198-b36">
            <citation citation-type="book">
               <collab>World Health Organization</collab>
               <source>Ethical criteria for medicinal drug promotion</source>
               <year>1988</year>
               <publisher-loc>Geneva</publisher-loc>
               <publisher-name>World Health Organization</publisher-name>
               <comment>Available: <ext-link ext-link-type="uri" xlink:href="http://mednet2.who.int/tbs/promo/whozip08e.pdf">http://mednet2.who.int/tbs/promo/whozip08e.pdf</ext-link>. Accessed 7 March
                  2006 </comment>
            </citation>
         </ref>
      </ref-list>
      <glossary>
         <title>Abbreviations</title>
         <def-list>
            <def-item>
               <term>DTCA</term>
               <def>
                  <p>direct-to-consumer advertising</p>
               </def>
            </def-item>
            <def-item>
               <term>FDA</term>
               <def>
                  <p>United States Food and Drug Administration</p>
               </def>
            </def-item>
            <def-item>
               <term>HRT</term>
               <def>
                  <p>hormone replacement therapy</p>
               </def>
            </def-item>
            <def-item>
               <term>NSAID</term>
               <def>
                  <p>nonsteroidal anti-inflammatory drug</p>
               </def>
            </def-item>
            <def-item>
               <term>PMDD</term>
               <def>
                  <p>premenstrual dysphoric dysfunction</p>
               </def>
            </def-item>
            <def-item>
               <term>SSRI</term>
               <def>
                  <p>selective serotonin reuptake inhibitor</p>
               </def>
            </def-item>
         </def-list>
      </glossary>
      <sec id="s10" sec-type="display-objects">
         <title>Figures and Tables</title>
         <fig id="pmed-0030198-g001" position="float">
            <label>Figure 1</label>
            <caption>
               <title>Disease-Awareness Campaign Sponsored by Pfizer, the Manufacturer of Lipitor</title>
               <p>(Image copyright: Pfizer Canada Inc./Making the Connection. All rights reserved.)</p>
            </caption>
            <graphic xlink:href="pmed.0030198.g001"/>
         </fig>
         <table-wrap id="pmed-0030198-t001" position="float">
            <label>Table 1</label>
            <caption>
               <title>FDA Letters of Violation on Consumer-Directed Advertising, January 2004 to mid-December 2005</title>
            </caption>
            <graphic xlink:href="pmed.0030198.t001"/>
         </table-wrap>
      </sec>
      <fn-group>
         <fn fn-type="financial-disclosure" id="n3">
            <p>
               <bold>Funding:</bold> The author received no specific funding for this article. </p>
         </fn>
         <fn fn-type="other" id="n4">
            <p>
               <bold>Citation:</bold> Mintzes B (2006) Disease mongering in drug promotion: Do governments have a regulatory role? PLoS Med 3(4): e198. </p>
         </fn>
      </fn-group>
   </back>
</article>
