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 left:86.89%;width:11.04%;height:5.5%'><span style=3D'text-effect:emboss;
 color:#006699'><b><i>UCSF</i></b></span><span style=3D'font-family:Palatin=
o;
 mso-ascii-font-family:Palatino;font-size:75%;text-shadow:auto;color:#FFFF6=
6;
 mso-special-format:lastCR;display:none'><b>&#13;</b></span></div>
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  style=3D'position:absolute;left:132pt;top:234pt;width:7in;height:210pt;
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e;
 top:5.25%;left:2.05%;width:98.31%;height:10.5%'><span style=3D'font-size:9=
0%'>How
 Do We Know What We Know?<br>
  </span></span><span style=3D'position:absolute;top:13.25%;left:7.67%;
 width:87.26%;height:10.5%'><span style=3D'font-size:90%'><span
 style=3D'mso-spacerun:yes'>&nbsp; </span><br>
  </span></span><span style=3D'position:absolute;top:21.25%;left:.74%;width=
:101.12%;
 height:10.5%'><span style=3D'font-size:90%'>The Impact of Industry Funding=
 on </span></span><span
 style=3D'position:absolute;top:29.25%;left:5.99%;width:90.63%;height:10.5%=
'><span
 style=3D'font-size:90%'>the Clinical Research Literature</span></span></di=
v>
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 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:42.0%;left:=
14.41%;
 width:78.08%;height:9.25%'>Thomas B. Newman, MD, MPH&#13;</div>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:49.75%;left:13.85%;width:79.21%;height:9.25%'>Professor of Epidemiology
 and </span><span style=3D'position:absolute;top:56.25%;left:18.16%;width:7=
0.59%;
 height:9.25%'>Biostatistics and Pediatrics, </span><span style=3D'position=
:absolute;
 top:62.74%;left:19.28%;width:68.16%;height:9.25%'>UCSF&#13;</span></div>
 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:70.5%;left:=
19.28%;
 width:68.16%;height:9.25%'>August 19, 2008</div>
 </div>
</p:slide></div>

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an
 style=3D'position:absolute;top:24.0%;left:11.42%;width:92.5%;height:9.25%'=
>Consumer
 and Prescriber Education </span><span style=3D'position:absolute;top:31.25=
%;
 left:11.42%;width:95.69%;height:9.25%'>Grant Program, funded by the multi-=
</span><span
 style=3D'position:absolute;top:38.25%;left:11.42%;width:91.57%;height:9.25=
%'>state
 settlement of consumer fraud </span><span style=3D'position:absolute;top:4=
5.5%;
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/span><span
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'>the
 prescription drug Neurontin&reg;.&#13;</span><span style=3D'position:absol=
ute;
 top:61.0%;left:11.42%;width:80.14%;height:9.25%'><span class=3DBB
 style=3D'position:absolute;left:-4.67%'>&#8226;</span>Help: Lisa Bero and
 Michael </span><span style=3D'position:absolute;top:68.25%;left:11.42%;
 width:80.14%;height:9.25%'>Steinman</span></div>
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5%;
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rmat:
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5%;
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75%;
 left:11.79%;width:81.46%;height:8.25%'><span style=3D'position:absolute;
 top:0%;left:7.12%;width:92.87%;height:100.0%'><span style=3D'mso-special-f=
ormat:
 bullet;position:absolute;left:-7.67%'>&#8211;</span><span lang=3DEN-GB>Sub=
jects&#13;</span></span></div>
 <div class=3DB1 style=3D'mso-margin-left-alt:624;position:absolute;top:39.=
25%;
 left:11.79%;width:81.46%;height:8.25%'><span style=3D'position:absolute;
 top:0%;left:7.12%;width:92.87%;height:100.0%'><span style=3D'mso-special-f=
ormat:
 bullet;position:absolute;left:-7.67%'>&#8211;</span><span lang=3DEN-GB>Pre=
dictor
 variables&#13;</span></span></div>
 <div class=3DB1 style=3D'mso-margin-left-alt:624;position:absolute;top:46.=
75%;
 left:11.79%;width:81.46%;height:8.25%'><span style=3D'position:absolute;
 top:0%;left:7.12%;width:92.87%;height:100.0%'><span style=3D'mso-special-f=
ormat:
 bullet;position:absolute;left:-7.67%'>&#8211;</span><span lang=3DEN-GB>Out=
come
 variable&#13;</span></span></div>
 <div class=3DB style=3D'mso-margin-left-alt:384;position:absolute;top:54.2=
5%;
 left:6.92%;width:99.81%;height:9.25%'><span style=3D'position:absolute;
 top:0%;left:6.56%;width:93.24%;height:100.0%'><span style=3D'mso-special-f=
ormat:
 bullet;position:absolute;left:-7.04%'>&#8226;</span><span lang=3DEN-GB>Ana=
lysis
 and presentation of results&#13;</span></span></div>
 <div class=3DB style=3D'mso-margin-left-alt:384;position:absolute;top:62.7=
4%;
 left:6.92%;width:86.51%;height:9.25%'><span style=3D'position:absolute;
 top:0%;left:7.57%;width:92.2%;height:100.0%'><span style=3D'mso-special-fo=
rmat:
 bullet;position:absolute;left:-8.21%'>&#8226;</span><span lang=3DEN-GB>Dis=
cussion
 and conclusions&#13;</span></span></div>
 <div class=3DB style=3D'mso-margin-left-alt:384;position:absolute;top:71.2=
5%;
 left:6.92%;width:86.51%;height:9.25%'><span style=3D'position:absolute;
 top:0%;left:7.57%;width:92.2%;height:100.0%'><span style=3D'mso-special-fo=
rmat:
 bullet;position:absolute;left:-8.21%'>&#8226;</span><span lang=3DEN-GB>Pub=
lication&#13;</span></span></div>
 <div class=3DB style=3D'mso-margin-left-alt:384;position:absolute;top:79.7=
5%;
 left:6.92%;width:86.51%;height:9.25%'><span style=3D'mso-special-format:no=
bullet;
 display:none'>&#8226;</span><span lang=3DEN-GB style=3D'mso-special-format=
:lastCR;
 display:none'>&#13;</span></div>
 </div>
</p:slide></div>

<![if !ppt]>

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<table style=3D'color:white' border=3D0 width=3D"100%">
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  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3>The le=
arning
  objectives of this talk are as follows</font><br>
  </td>
 </tr>
</table>

</div>

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.0%;
 left:7.3%;width:83.14%;height:10.5%'><span style=3D'font-size:90%'>Selecti=
on of
 Research Topics</span></div>
 <div v:shape=3D"_x0000_s128003">
 <div class=3DB><span style=3D'position:absolute;top:17.0%;left:8.05%;width=
:101.12%;
 height:9.25%'><span class=3DBB style=3D'position:absolute;left:-3.7%'>&#82=
26;</span>Availability
 of funding is a major driver </span><span style=3D'position:absolute;top:2=
4.0%;
 left:8.05%;width:86.89%;height:9.25%'>of the research agenda&#13;</span></=
div>
 <div class=3DB><span style=3D'position:absolute;top:32.5%;left:8.05%;width=
:94.19%;
 height:9.25%'><span class=3DBB style=3D'position:absolute;left:-3.97%'>&#8=
226;</span>Limited
 funding for health problems </span><span style=3D'position:absolute;top:39=
.75%;
 left:8.05%;width:86.89%;height:9.25%'>that occur in places with limited </=
span><span
 style=3D'position:absolute;top:46.75%;left:8.05%;width:102.05%;height:9.25=
%'>resources
 or that do not have solutions </span><span style=3D'position:absolute;
 top:54.0%;left:8.05%;width:86.89%;height:9.25%'>that include marketable
 products&#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:62.5%;left:9.36%;width:85.7=
6%;
 height:9.25%'><span style=3D'position:absolute;top:0%;left:3.49%;width:96.=
28%;
 height:100.0%'><span style=3D'font-size:114%'><span class=3DB1B style=3D'p=
osition:
 absolute;left:-3.62%'>&#8211;</span></span><span style=3D'font-size:114%'>=
Tropical
 diseases&#13;</span></span></div>
 <div class=3DB1 style=3D'position:absolute;top:71.0%;left:9.36%;width:85.7=
6%;
 height:9.25%'><span style=3D'position:absolute;top:0%;left:3.49%;width:96.=
28%;
 height:100.0%'><span style=3D'font-size:114%'><span class=3DB1B style=3D'p=
osition:
 absolute;left:-3.62%'>&#8211;</span></span><span style=3D'font-size:114%'>=
<span
 style=3D'mso-spacerun:yes'>&nbsp;</span>Environmental health&#13;</span></=
span></div>
 <div class=3DB1 style=3D'position:absolute;top:79.5%;left:9.36%;width:85.7=
6%;
 height:9.25%'><span style=3D'position:absolute;top:0%;left:3.49%;width:96.=
28%;
 height:100.0%'><span style=3D'font-size:114%'><span class=3DB1B style=3D'p=
osition:
 absolute;left:-3.62%'>&#8211;</span></span><span style=3D'font-size:114%'>=
<span
 style=3D'mso-spacerun:yes'>&nbsp;</span>Public health</span></span></div>
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 style=3D'font-family:Palatino;mso-ascii-font-family:Palatino;font-size:75%;
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000_s271364"
  type=3D"#_x0000_t202" style=3D'position:absolute;left:96pt;top:468pt;widt=
h:546pt;
  height:36pt;visibility:visible' filled=3D"f" fillcolor=3D"#0c9 [4]" strok=
ed=3D"f"
  strokecolor=3D"white [1]">
  <v:fill color2=3D"#009 [0]"/>
  <v:shadow color=3D"gray [2]"/>
  <v:textbox style=3D'mso-fit-shape-to-text:t'/>
 </v:shape>
 <div v:shape=3D"_x0000_s271362" class=3DT><span style=3D'position:absolute;
 top:2.0%;left:5.61%;width:85.58%;height:9.25%'><span style=3D'font-size:80=
%'>Drug
 Development for Neglected </span></span><span style=3D'position:absolute;
 top:9.0%;left:6.92%;width:83.14%;height:9.25%'><span style=3D'font-size:80=
%'>Diseases*</span></span></div>
 <div v:shape=3D"_x0000_s271363" class=3DB><span style=3D'position:absolute;
 top:19.5%;left:11.42%;width:87.45%;height:8.25%'><span style=3D'font-size:=
88%'><span
 class=3DBB style=3D'position:absolute;left:-4.28%'>&#8226;</span></span><s=
pan
 style=3D'font-size:88%'>Compared new chemical entities (NCE) </span></span=
><span
 style=3D'position:absolute;top:25.75%;left:11.42%;width:91.57%;height:8.25=
%'><span
 style=3D'font-size:88%'>for different indications, with number of </span><=
/span><span
 style=3D'position:absolute;top:32.0%;left:11.42%;width:91.19%;height:8.25%=
'><span
 style=3D'font-size:88%'>disability-adjusted life years (DALY) lost </span>=
</span><span
 style=3D'position:absolute;top:38.0%;left:11.42%;width:79.4%;height:8.25%'=
><span
 style=3D'font-size:88%'>1975-1999&#13;</span></span><span style=3D'positio=
n:absolute;
 top:45.5%;left:11.42%;width:79.4%;height:8.25%'><span style=3D'font-size:8=
8%'><span
 class=3DBB style=3D'position:absolute;left:-4.71%'>&#8226;</span></span><s=
pan
 style=3D'font-size:88%'>Of 1393 NCE, only 16 for tropical </span></span><s=
pan
 style=3D'position:absolute;top:51.74%;left:11.42%;width:79.4%;height:8.25%=
'><span
 style=3D'font-size:88%'>diseases and TB&#13;</span></span><span
 style=3D'position:absolute;top:59.25%;left:11.42%;width:90.07%;height:8.25=
%'><span
 style=3D'font-size:88%'><span class=3DBB style=3D'position:absolute;left:-=
4.15%'>&#8226;</span></span><span
 style=3D'font-size:88%'>1.2-1.4 NCE/Million DALY lost for main </span></sp=
an><span
 style=3D'position:absolute;top:65.5%;left:11.42%;width:94.75%;height:8.25%=
'><span
 style=3D'font-size:88%'>diseases of wealthier countries, vs 0.1 for </span=
></span><span
 style=3D'position:absolute;top:71.75%;left:11.42%;width:79.4%;height:8.25%=
'><span
 style=3D'font-size:88%'>tropical diseases</span></span></div>
 <div v:shape=3D"_x0000_s271364" class=3DO style=3D'position:absolute;top:8=
7.5%;
 left:14.41%;width:76.59%;height:5.25%'>*Trouiller P et al. Lancet
 2002;359:2188-94</div>
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 of
 Studies </span></div>
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8%'><span
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/span></span><span
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><span
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an></span></div>
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span><span
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<span
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 <div v:shape=3D"_x0000_s339970" class=3DT><span style=3D'position:absolute;
 top:3.25%;left:6.92%;width:83.14%;height:10.5%'><span style=3D'font-size:9=
0%'>Exclusion
 Criteria Used In </span></span><span style=3D'position:absolute;top:11.25%;
 left:5.43%;width:86.14%;height:10.5%'><span style=3D'font-size:90%'>Antide=
pressant
 Efficacy Trials</span></span></div>
 <div v:shape=3D"_x0000_s339974">
 <div class=3DB style=3D'mso-line-spacing:"90 20 0"'><span style=3D'positio=
n:absolute;
 top:23.5%;left:11.42%;width:86.14%;height:8.25%'><span style=3D'font-size:=
88%'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.34%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Abstracted exclusion criteria for 39 </span></span=
><span
 style=3D'position:absolute;top:28.99%;left:11.42%;width:92.32%;height:8.25=
%'><span
 style=3D'font-size:88%'>antidepressant efficacy trials in adults (5 </span=
></span><span
 style=3D'position:absolute;top:34.75%;left:11.42%;width:86.14%;height:8.25=
%'><span
 style=3D'font-size:88%'>journals 1994-2000)&#13;</span></span></div>
 <div class=3DB style=3D'mso-line-spacing:"90 20 0"'><span style=3D'positio=
n:absolute;
 top:41.5%;left:11.42%;width:86.14%;height:8.25%'><span style=3D'font-size:=
88%'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.34%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Applied criteria from each trial to 503 </span></s=
pan><span
 style=3D'position:absolute;top:47.0%;left:11.42%;width:90.44%;height:8.25%=
'><span
 style=3D'font-size:88%'>outpatients with nonpsychotic, unipolar </span></s=
pan><span
 style=3D'position:absolute;top:52.75%;left:11.42%;width:86.14%;height:8.25=
%'><span
 style=3D'font-size:88%'>major depression&#13;</span></span></div>
 <div class=3DB style=3D'mso-line-spacing:"90 20 0";position:absolute;top:5=
9.5%;
 left:7.67%;width:96.06%;height:8.25%'><span style=3D'position:absolute;
 top:0%;left:3.89%;width:96.1%;height:100.0%'><span style=3D'font-size:88%'=
><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.05%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Median % excluded 70% (range 0 to 95%)&#13;</span>=
</span></div>
 <div class=3DB style=3D'mso-line-spacing:"90 20 0";position:absolute;top:6=
6.5%;
 left:7.67%;width:89.88%;height:8.25%'><span style=3D'position:absolute;
 top:0%;left:4.16%;width:95.83%;height:100.0%'><span style=3D'font-size:88%=
'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.34%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Main reasons:&#13;</span></span></div>
 <div class=3DB1 style=3D'mso-line-spacing:"90 20 0";position:absolute;top:=
73.25%;
 left:12.73%;width:84.83%;height:7.0%'><span style=3D'position:absolute;
 top:0%;left:3.53%;width:96.24%;height:100.0%'><span style=3D'font-size:86%=
'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-3.66%'>&#8211;<=
/span></span><span
 style=3D'font-size:86%'>Insufficient severity of depression&#13;</span></s=
pan></div>
 <div class=3DB1 style=3D'mso-line-spacing:"90 20 0";position:absolute;top:=
79.25%;
 left:12.73%;width:84.83%;height:7.0%'><span style=3D'position:absolute;
 top:0%;left:3.53%;width:96.24%;height:100.0%'><span style=3D'font-size:86%=
'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-3.66%'>&#8211;<=
/span></span><span
 style=3D'font-size:86%'>Comorbid psychiatric illness or suicidality</span>=
</span></div>
 </div>
 <div v:shape=3D"_x0000_s339975" class=3DO style=3D'mso-line-spacing:"100 5=
0 0"'><span
 style=3D'position:absolute;top:86.5%;left:3.55%;width:94.56%;height:5.25%'=
>Zimmerman
 M et al. J Nerv Ment Dis 2004;192:87-94 </span><span style=3D'position:abs=
olute;
 top:91.75%;left:3.55%;width:92.32%;height:5.25%'>Zimmerman M et al. Am J P=
sych
 2005;162:1370-72</span></div>
</p:slide></div>

<![if !ppt]>

<div id=3DNotesObj style=3D'display:none'>

<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3>From 2=
004 paper:
  Trials included:<span style=3D'mso-spacerun:yes'>&nbsp; </span>all treatm=
ent
  efficacy trials published in Arch Gen Psych, Am J Psych, J Clin Psychiatr=
y, J
  Clin Psychopharm,<span style=3D'mso-spacerun:yes'>&nbsp; </span>and Psych=
opharm
  Bulletin 1994 -2000.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Per pe=
rsonal
  communication with M Zimmerman, almost all of these patients were treated
  with antidepressants.<span style=3D'mso-spacerun:yes'>&nbsp; </span>The
  patients were those with nonpsychotic unipolar MDD from 1500 who were
  evaluated with Structured Clinical Interviews as part of the MIDAS projec=
t.</font><br>
  </td>
 </tr>
</table>

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d </span><span
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>Doses
 Being Compared</span></div>
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th:87.45%;
 height:9.25%'><span class=3DBB style=3D'position:absolute;left:-4.28%'>&#8=
226;</span>Selection
 of comparison drug and </span><span style=3D'position:absolute;top:35.25%;
 left:12.17%;width:79.4%;height:9.25%'>dose &#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:43.75%;left:13.48%;width:78=
.08%;
 height:8.25%'><span style=3D'position:absolute;top:0%;left:4.07%;width:96.=
16%;
 height:100.0%'><span class=3DB1B style=3D'position:absolute;left:-4.23%'>&=
#8211;</span>Lower
 dose &#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:51.24%;left:13.48%;width:78=
.08%;
 height:8.25%'><span style=3D'position:absolute;top:0%;left:4.07%;width:96.=
16%;
 height:100.0%'><span class=3DB1B style=3D'position:absolute;left:-4.23%'>&=
#8211;</span>More
 toxic &#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:58.75%;left:13.48%;width:78=
.08%;
 height:8.25%'><span style=3D'position:absolute;top:0%;left:4.07%;width:96.=
16%;
 height:100.0%'><span class=3DB1B style=3D'position:absolute;left:-4.23%'>&=
#8211;</span>Ineffective</span></div>
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  <v:textbox style=3D'mso-fit-shape-to-text:t'/>
 </v:shape>
 <div v:shape=3D"_x0000_s135170" class=3DT style=3D'position:absolute;top:7=
.75%;
 left:3.55%;width:93.07%;height:11.5%'>RCTs of NSAIDS, 1987-1990</div>
 <div v:shape=3D"_x0000_s135171">
 <div class=3DB><span style=3D'position:absolute;top:22.5%;left:9.73%;width=
:95.13%;
 height:9.25%'><span class=3DBB style=3D'position:absolute;left:-3.93%'>&#8=
226;</span>Meta-analysis
 of 56 trials associated </span><span style=3D'position:absolute;top:29.75%;
 left:9.73%;width:79.4%;height:9.25%'>with a manufacturer&#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:38.25%;left:11.04%;width:78=
.08%;
 height:8.25%'><span style=3D'position:absolute;top:0%;left:3.83%;width:96.=
16%;
 height:100.0%'><span class=3DB1B style=3D'position:absolute;left:-3.99%'>&=
#8211;</span>16
 manufacturer&#8217;s drug better&#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:45.75%;left:11.04%;width:78=
.08%;
 height:8.25%'><span style=3D'position:absolute;top:0%;left:3.83%;width:96.=
16%;
 height:100.0%'><span class=3DB1B style=3D'position:absolute;left:-3.99%'>&=
#8211;</span>40
 both drugs about the same &#13;</span></div>
 <div class=3DB1 style=3D'position:absolute;top:53.25%;left:11.04%;width:78=
.08%;
 height:8.25%'><span style=3D'position:absolute;top:0%;left:3.83%;width:96.=
16%;
 height:100.0%'><span class=3DB1B style=3D'position:absolute;left:-3.99%'>&=
#8211;</span><span
 style=3D'mso-spacerun:yes'>&nbsp; </span>0 competitor&#8217;s drug better&=
#13;</span></div>
 <div class=3DB style=3D'position:absolute;top:60.75%;left:5.99%;width:83.1=
4%;
 height:9.25%'><span style=3D'position:absolute;top:0%;left:4.5%;width:95.4=
9%;
 height:100.0%'><span class=3DBB style=3D'position:absolute;left:-4.71%'>&#=
8226;</span>How
 did they get this result?</span></div>
 </div>
 <div v:shape=3D"_x0000_s135172" class=3DO style=3D'mso-line-spacing:"100 5=
0 0";
 position:absolute;top:89.5%;left:4.3%;width:98.12%;height:7.0%'><span
 style=3D'font-family:"Lucida Sans Unicode";mso-ascii-font-family:"Lucida S=
ans Unicode";
 color:#FFCC00;mso-color-index:3'><i>Rochon et al. Arch Intern Med 1994; 15=
4:
 157-63.</i></span></div>
</p:slide></div>

<![if !ppt]>

<div id=3DNotesObj style=3D'display:none'>

<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3><i>Roc=
hon PA,
  Gurwitz JH, Simms RW, Fortin PR, Felson DT, Minaker KL, Chalmers TC.</i><=
/font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3><i>A s=
tudy of
  manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in =
the
  treatment of arthritis.</i></font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3><i>BAC=
KGROUND: To
  study the relation between reported drug performance in published trials =
and
  support of the trials by the manufacturer of the drug under evaluation, we
  studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAID=
s)
  used in the treatment of arthritis. METHODS: All randomized control trial=
s of
  NSAIDs published between September 1987 and May 1990 identified by MEDLINE
  were reviewed. If an article met the following criteria (n =3D 61), it was
  selected: trials involving adult patients with osteoarthritis or rheumato=
id
  arthritis (n =3D 180), use of nonsalicylate NSAIDs marketed in the United
  States (n =3D 101), randomized control trial (n =3D 81), duration of the =
trial 4
  or more days (n =3D 78), and use of an efficacy outcome measure (n =3D 61=
).
  Reviewers, &quot;blinded&quot; to manufacturer status, evaluated the
  narrative interpretation of results and extracted numeric data on efficacy
  and toxicity. Manufacturer-associated trials were defined as those that
  acknowledged an association with a pharmaceutical manufacturer. Because of
  the scarcity of non-manufacturer-associated trials (n =3D 9), we report o=
nly on
  the manufacturer-associated articles. RESULTS: Fifty-two publications (85=
.2%)
  representing 56 trials were associated with a manufacturer. The
  manufacturer-associated drug was reported as comparable with (71.4%) or
  superior to (28.6%) the comparison drug in all 56 trials. These narrative
  claims of superiority were usually justified with trial data. Of the tria=
ls
  identifying one drug as less toxic (n =3D 22), the manufacturer-associated
  drug's safety was reported as superior to the comparison drug in 86.4% of
  cases. Justification for the narrative interpretation of the trial findin=
gs
  regarding less toxicity was provided in only 12 (54.5%) of 22 trials.
  CONCLUSION: The manufacturer-associated NSAID is almost always reported as
  being equal or superior in efficacy and toxicity to the comparison drug.
  These claims of superiority, especially in regard to side effect profiles,
  are often not supported by trial data. These data raise concerns about
  selective publication or biased interpretation of results in
  manufacturer-associated trials.</i></font><br>
  </td>
 </tr>
</table>

</div>

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<![if !ppt]>

<div id=3DNotesObj style=3D'display:none'>

<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3>In try=
ing to explain
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nd
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sed a
  5-point scale: 1 below the recommended dose, 2 low end of dosage range, 3=
 mid
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se,
  based on standard references (most commonly the PDR.)<span
  style=3D'mso-spacerun:yes'>&nbsp;&nbsp; </span>In about half of trials, t=
he
  comparator drug was given at lower relative dose than the
  manufacturer&#8217;s<span style=3D'mso-spacerun:yes'>&nbsp; </span>drug (=
for
  example, ibuprofen 400 q 8 h vs naproxen 500 mg q 12).<span
  style=3D'mso-spacerun:yes'>&nbsp; </span>In about half of trials, the two=
 drugs
  were given at comparable doses.<span style=3D'mso-spacerun:yes'>&nbsp;
  </span>In less than 5% of trials, the comparator drug was given at a high=
er
  relative dose.</font><br>
  </td>
 </tr>
 <tr>
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  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3>Thus, =
it is not
  surprising that the manufacturer&#8217;s drug was found to be superior in
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  </td>
 </tr>
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 <div v:shape=3D"_x0000_s141314" class=3DT><span style=3D'position:absolute;
 top:3.25%;left:8.42%;width:83.14%;height:10.5%'><span style=3D'font-size:9=
0%'>Predictor
 Variable: <br>
  </span></span><span style=3D'position:absolute;top:11.25%;left:8.42%;
 width:83.14%;height:10.5%'><span style=3D'font-size:90%'>Choice of Compari=
son
 Drug</span></span></div>
 <div v:shape=3D"_x0000_s141315" class=3DB><span style=3D'position:absolute;
 top:26.0%;left:8.98%;width:92.69%;height:8.25%'><span style=3D'font-size:8=
8%'><span
 class=3DBB style=3D'position:absolute;left:-4.04%'>&#8226;</span></span><s=
pan
 style=3D'font-size:88%'>Selective Cox-2 inhibitors like Rofecoxib </span><=
/span><span
 style=3D'position:absolute;top:32.25%;left:8.98%;width:84.45%;height:8.25%=
'><span
 style=3D'font-size:88%'>(Vioxx&reg;) may increase the risk of </span></spa=
n><span
 style=3D'position:absolute;top:38.5%;left:8.98%;width:86.32%;height:8.25%'=
><span
 style=3D'font-size:88%'>cardiovascular disease compared with </span></span=
><span
 style=3D'position:absolute;top:44.75%;left:8.98%;width:84.45%;height:8.25%=
'><span
 style=3D'font-size:88%'>naproxen or placebo&#13;</span></span><span
 style=3D'position:absolute;top:52.25%;left:8.98%;width:96.62%;height:8.25%=
'><span
 style=3D'font-size:88%'><span class=3DBB style=3D'position:absolute;left:-=
3.87%'>&#8226;</span></span><span
 style=3D'font-size:88%'>New COX-2 inhibitor Etoricoxib (Arcoxia&reg;) </sp=
an></span><span
 style=3D'position:absolute;top:58.5%;left:8.98%;width:98.68%;height:8.25%'=
><span
 style=3D'font-size:88%'>studied in long term trial study (N=3D34,700)&#13;=
</span></span><span
 style=3D'position:absolute;top:66.0%;left:8.98%;width:84.45%;height:8.25%'=
><span
 style=3D'font-size:88%'><span class=3DBB style=3D'position:absolute;left:-=
4.43%'>&#8226;</span></span><span
 style=3D'font-size:88%'>Merck chose diclofenac rather than </span></span><=
span
 style=3D'position:absolute;top:72.25%;left:8.98%;width:84.45%;height:8.25%=
'><span
 style=3D'font-size:88%'>naproxen as comparator &#13;</span></span>
 <div style=3D'position:absolute;top:79.75%;left:5.24%;width:88.2%;height:8=
.25%'><span
 style=3D'position:absolute;top:0%;left:4.24%;width:95.75%;height:100.0%'><=
span
 style=3D'font-size:88%'><span class=3DBB style=3D'position:absolute;left:-=
4.43%'>&#8226;</span></span><span
 style=3D'font-size:88%'>Why?</span></span></div>
 </div>
 <div v:shape=3D"_x0000_s141316" class=3DO style=3D'mso-line-spacing:"100 5=
0 0";
 position:absolute;top:92.0%;left:3.55%;width:95.88%;height:5.25%'>Psaty BM,
 Weiss NS. N Engl J Med 2007; 356:328-30</div>
</p:slide></div>

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<div id=3DNotesObj style=3D'display:none'>

<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3>Multin=
ational
  Etoricoxib and Diclofenac Arthritis Long-Term</font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D2>Psaty =
BM, Weiss
  NS.<span style=3D'mso-spacerun:yes'>&nbsp; </span>NSAID trials and choice=
 of
  comparators &#8211; Questions of public health importance. N Engl J Med 2=
007;
  356:328-30</font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D2>FDA ha=
d approved the
  MEDAL study, but when it sought FDA approval for Arcoxia (which had effic=
acy
  and side effects similar to diclofenac), FDA allowed David Graham to argue
  against it and the committee overwhelmingly rejected it.<span
  style=3D'mso-spacerun:yes'>&nbsp; </span>(Avorn NEJM 8/14/07 Keeping Scie=
nce on
  Top in Drug Evaluation</font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><br>
  </td>
 </tr>
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nt-size:
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67%;
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 <div class=3DTbl style=3D'mso-margin-left-alt:0;position:absolute;top:80.0=
%;
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 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
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 <div class=3DTbl style=3D'text-align:center;mso-margin-left-alt:0;position=
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 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
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 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
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 <div class=3DTbl style=3D'mso-margin-left-alt:0;position:absolute;top:72.5=
%;
 left:12.73%;width:33.52%;height:8.25%'>Naproxen</div>
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 <div v:shape=3D"_x0000_s143371">
 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
 <div class=3DTbl4 style=3D'mso-margin-left-alt:1152'></div>
 <div class=3DTbl style=3D'text-align:center;mso-margin-left-alt:0;position=
:absolute;
 top:65.0%;left:45.5%;width:38.76%;height:8.25%'>1.63 (1.12, 2.37)</div>
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 <div v:shape=3D"_x0000_s143370">
 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
 <div class=3DTbl4 style=3D'mso-margin-left-alt:1152'></div>
 <div class=3DTbl style=3D'mso-margin-left-alt:0;position:absolute;top:65.0=
%;
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 <div v:shape=3D"_x0000_s143369">
 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
 <div class=3DTbl4 style=3D'mso-margin-left-alt:1152'></div>
 <div class=3DTbl style=3D'text-align:center;mso-margin-left-alt:0;position=
:absolute;
 top:51.0%;left:45.5%;width:38.76%;height:8.25%'>1.42 (1.13, 1.78)</div>
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 <div v:shape=3D"_x0000_s143368">
 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
 <div class=3DTbl4 style=3D'mso-margin-left-alt:1152'></div>
 <div class=3DTbl style=3D'mso-margin-left-alt:0'><span style=3D'position:a=
bsolute;
 top:51.0%;left:12.73%;width:36.7%;height:8.25%'>Selective COX-2 </span><sp=
an
 style=3D'position:absolute;top:57.25%;left:12.73%;width:33.52%;height:8.25=
%'>Inhibitors</span></div>
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 <div v:shape=3D"_x0000_s143367">
 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
 <div class=3DTbl4 style=3D'mso-margin-left-alt:1152'></div>
 <div class=3DTbl style=3D'text-align:center;mso-margin-left-alt:0'><span
 style=3D'position:absolute;top:25.0%;left:45.69%;width:38.57%;height:8.75%=
'><span
 style=3D'font-size:107%'><b>RR of CV Events </b></span></span><span
 style=3D'position:absolute;top:31.5%;left:48.12%;width:33.52%;height:8.75%=
'><span
 style=3D'font-size:107%'><b>c/w Placebo </b></span></span><span
 style=3D'position:absolute;top:38.25%;left:48.12%;width:33.52%;height:8.75=
%'><span
 style=3D'font-size:107%'><b>(95% CI)</b></span></span></div>
 </div>
 <div v:shape=3D"_x0000_s143366">
 <div class=3DTbl1 style=3D'mso-margin-left-alt:288'></div>
 <div class=3DTbl2 style=3D'mso-margin-left-alt:576'></div>
 <div class=3DTbl3 style=3D'mso-margin-left-alt:864'></div>
 <div class=3DTbl4 style=3D'mso-margin-left-alt:1152'></div>
 <div class=3DTbl style=3D'text-align:center;mso-margin-left-alt:0;position=
:absolute;
 top:25.0%;left:12.73%;width:33.52%;height:8.75%'><span style=3D'font-size:=
107%'><b>Drug</b></span></div>
 </div>
</p:slide></div>

<![if !ppt]>

<div id=3DNotesObj style=3D'display:none'>

<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D2>Diclof=
enac has
  cardiovascular toxicity similar to selective COX-2 inhibitors</font><br>
  </td>
 </tr>
</table>

</div>

<![endif]>
</body>

</html>

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roked=3D"f"
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  <v:textbox style=3D'mso-fit-shape-to-text:t'/>
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 <div v:shape=3D"_x0000_s353282" class=3DT><span style=3D'position:absolute;
 top:2.0%;left:3.55%;width:83.14%;height:10.5%'><span style=3D'font-size:90=
%'>Choice
 of Comparison Drug:<br>
  </span></span><span style=3D'position:absolute;top:10.0%;left:3.55%;width=
:83.14%;
 height:10.5%'><span style=3D'font-size:90%'><span
 style=3D'mso-spacerun:yes'>&nbsp;</span>Ineffective</span></span></div>
 <div v:shape=3D"_x0000_s353283" class=3DB>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:23.5%;left:12.17%;width:79.4%;height:8.25%'><span style=3D'font-size:8=
8%'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.71%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Meta-analysis of fluconazole vs. </span></span><sp=
an
 style=3D'position:absolute;top:28.99%;left:12.17%;width:80.71%;height:8.25=
%'><span
 style=3D'font-size:88%'>amphotericin in neutropenic cancer </span></span><=
span
 style=3D'position:absolute;top:34.75%;left:12.17%;width:79.4%;height:8.25%=
'><span
 style=3D'font-size:88%'>patients*&#13;</span></span></div>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:41.5%;left:12.17%;width:79.58%;height:8.25%'><span style=3D'font-size:=
88%'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.7%'>&#8226;</=
span></span><span
 style=3D'font-size:88%'>Almost all studies (92% of included </span></span>=
<span
 style=3D'position:absolute;top:47.0%;left:12.17%;width:79.4%;height:8.25%'=
><span
 style=3D'font-size:88%'>patients) sponsored by Pfizer&#13;</span></span></=
div>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:54.0%;left:12.17%;width:92.5%;height:8.25%'><span style=3D'font-size:8=
8%'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.04%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Amphotericin given orally to comparison </span></s=
pan><span
 style=3D'position:absolute;top:59.5%;left:12.17%;width:79.4%;height:8.25%'=
><span
 style=3D'font-size:88%'>groups (79% of patients)&#13;</span></span></div>
 <div style=3D'mso-line-spacing:"90 20 0"'><span style=3D'position:absolute;
 top:66.5%;left:12.17%;width:79.4%;height:8.25%'><span style=3D'font-size:8=
8%'><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.71%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Amphotericin groups sometimes </span></span><span
 style=3D'position:absolute;top:72.0%;left:12.17%;width:80.71%;height:8.25%=
'><span
 style=3D'font-size:88%'>combined with oral nystatin groups&#13;</span></sp=
an></div>
 <div style=3D'mso-line-spacing:"90 20 0";position:absolute;top:78.75%;
 left:8.42%;width:83.14%;height:8.25%'><span style=3D'position:absolute;
 top:0%;left:4.5%;width:95.49%;height:100.0%'><span style=3D'font-size:88%'=
><span
 style=3D'mso-special-format:bullet;position:absolute;left:-4.71%'>&#8226;<=
/span></span><span
 style=3D'font-size:88%'>Both are poorly absorbed orally</span></span></div>
 </div>
 <div v:shape=3D"_x0000_s353284" class=3DO style=3D'position:absolute;top:9=
5.25%;
 left:4.3%;width:91.57%;height:4.5%'><span style=3D'font-size:83%'>*Johanse=
n HK,
 Gotzsche PC.<span style=3D'mso-spacerun:yes'>&nbsp; </span>JAMA 1999;282:1=
752-59</span></div>
</p:slide></div>

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<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D3>Proble=
ms in the
  Design and Reporting of Trials of Antifungal Agents Encountered During
  Meta-analysis.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Similar issu=
es
  later reported with voriconazole, also by Pfizer.</font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><br>
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 style=3D'font-family:Palatino;mso-ascii-font-family:Palatino;font-size:75%;
 text-shadow:auto;color:#FFFF66;mso-special-format:lastCR;display:none'><b>=
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1.0%;
 left:8.42%;width:83.14%;height:11.5%'>Outcome variable</div>
 <div v:shape=3D"_x0000_s144387" class=3DB><span style=3D'position:absolute;
 top:28.24%;left:12.17%;width:79.4%;height:9.25%'><span class=3DBB
 style=3D'position:absolute;left:-4.71%'>&#8226;</span>Surrogate outcomes vs
 patient </span><span style=3D'position:absolute;top:35.25%;left:12.17%;
 width:79.4%;height:9.25%'>relevant&#13;</span>
 <div style=3D'position:absolute;top:43.75%;left:8.42%;width:83.14%;height:=
9.25%'><span
 style=3D'position:absolute;top:0%;left:4.5%;width:95.49%;height:100.0%'><s=
pan
 class=3DBB style=3D'position:absolute;left:-4.71%'>&#8226;</span>Composite
 outcomes&#13;</span></div>
 <span style=3D'position:absolute;top:52.25%;left:12.17%;width:85.76%;heigh=
t:
 9.25%'><span class=3DBB style=3D'position:absolute;left:-4.36%'>&#8226;</s=
pan>Multiple
 outcomes, time periods, </span><span style=3D'position:absolute;top:59.5%;
 left:12.17%;width:79.4%;height:9.25%'>subgroups, etc</span></div>
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0%'>Surrogate
 Outcomes:<span style=3D'mso-spacerun:yes'>&nbsp; </span>Cardiac </span></s=
pan><span
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5%'><span
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8%'><span
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8%'><span
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 DS et al. N Engl J Med. 1991;324:781-8&#13;</div>
 <div style=3D'position:absolute;top:94.25%;left:.93%;width:107.11%;height:=
5.25%'>Moore
 TJ.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Deadly Medicine. NY: Sim=
on and
 Schuster, 1995</div>
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<![if !ppt]>

<div id=3DNotesObj style=3D'display:none'>

<table style=3D'color:white' border=3D0 width=3D"100%">
 <tr>
  <td width=3D5 nowrap></td>
  <td width=3D"100%"></td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D1>1: N E=
ngl J Med.
  1991 Mar 21;324(12):781-8. Comment in: N Engl J Med. 1991 Aug
  22;325(8):584-5. N Engl J Med. 1992 Dec 17;327(25):1818. Mortality and
  morbidity in patients receiving encainide, flecainide, or placebo. The
  Cardiac Arrhythmia Suppression Trial. Echt DS, Liebson PR, Mitchell LB,
  Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Gr=
eene
  HL, et al. CAST Coordinating Center, Seattle, WA 98105. BACKGROUND AND
  METHODS. In the Cardiac Arrhythmia Suppression Trial, designed to test the
  hypothesis that suppression of ventricular ectopy after a myocardial
  infarction reduces the incidence of sudden death, patients in whom
  ventricular ectopy could be suppressed with encainide, flecainide, or
  moricizine were randomly assigned to receive either active drug or placeb=
o.
  The use of encainide and flecainide was discontinued because of excess
  mortality. We examined the mortality and morbidity after randomization to
  encainide or flecainide or their respective placebo. RESULTS. Of 1498 pat=
ients,
  857 were assigned to receive encainide or its placebo (432 to active drug=
 and
  425 to placebo) and 641 were assigned to receive flecainide or its placebo
  (323 to active drug and 318 to placebo). After a mean follow-up of 10 mon=
ths,
  89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving
  placebo; P =3D 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving =
drug
  vs. 5 receiving placebo; P =3D 0.01), and 8 of noncardiac causes (3 recei=
ving
  drug vs. 5 receiving placebo). Almost all cardiac deaths not due to
  arrhythmia were attributed to acute myocardial infarction with shock (11
  patients receiving drug and 3 receiving placebo) or to chronic congestive
  heart failure (4 receiving drug and 2 receiving placebo). There were no
  differences between the patients receiving active drug and those receiving
  placebo in the incidence of nonlethal disqualifying ventricular tachycard=
ia,
  proarrhythmia, syncope, need for a permanent pacemaker, congestive heart
  failure, recurrent myocardial infarction, angina, or need for coronary-ar=
tery
  bypass grafting or angioplasty. CONCLUSIONS. There was an excess of deaths
  due to arrhythmia and deaths due to shock after acute recurrent myocardial
  infarction in patients treated with encainide or flecainide. Nonlethal
  events, however, were equally distributed between the active-drug and pla=
cebo
  groups. The mechanisms underlying the excess mortality during treatment w=
ith
  encainide or flecainide remain unknown.</font><br>
  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
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  </td>
 </tr>
 <tr>
  <td colspan=3D1></td>
  <td dir=3Dltr align=3Dleft colspan=3D1><font face=3DArial size=3D1>Total =
mortality
  63/755 vs 26/717 P=3D0.000086 after 10 months</font><br>
  </td>
 </tr>
</table>

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