Declaration of Philip T. Lavin, Ph.D.
`US Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`Paper No._______
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
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` BIODELIVERY SCIENCES INTERNATIONAL, INC.
`Petitioner
`
`v.
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`RB PHARMACEUTICALS LIMITED
`Patent Owner
`
`US Patent No. 8,475,832
`Issue Date: July 2, 2013
`
`Title: SUBLINGUAL AND BUCCAL FILM COMPOSITIONS
`_______________
`
`Inter Partes Review No. Unassigned
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`DECLARATION BY PHILIP T. LAVIN, PH.D.
`UNDER 37 CFR § 1.132
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`Declaration of Philip T. Lavin, Ph.D.
`US Patent No. 8,475,832
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`I, Philip T. Lavin, do hereby make the following declaration:
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`Attorney Docket No. 117744-00041
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`1.
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`I have over 35 years of experience in the field of biostatistics as a Brown
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`University, Harvard School of Public Health, and Harvard Medical School
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`faculty member, a Principal Investigator, an FDA Advisory panel member,
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`and an expert consultant to the pharmaceutical, biotechnology, and medical
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`device industries leading to the approval of over 40 products to date. I
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`currently am the founding member and senior executive of a Boston-based
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`biostatistics consulting practice and a research foundation.
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`2.
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`I have participated in the design, analysis, presentation and publication of
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`clinical studies since 1974 after receiving my PhD in Applied Mathematics
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`from Brown University. I have authored or co-authored over 150 peer-
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`reviewed publications and have been internationally recognized for my
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`contributions to developing biomarkers (CA-125 and PSA), assessing
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`prognostic factors for oncology studies, treating cardioplegia, designing more
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`efficient Phase II cancer studies by measuring tumor response, and optimizing
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`liver and kidney transplants. I have been the senior biostatistician for 36
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`PMA/HDE approvals. In addition, I have served on multiple FDA Advisory
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`panels since 1983 and have served as the Principal Investigator for Data
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`Declaration of Philip T. Lavin, Ph.D.
`US Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`Coordinating Centers for multiple government-sponsored clinical studies. My
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`curriculum vitae is attached.
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`3. By experience developing and analyzing diagnostic tests and biomarkers for
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`over 30 years, I am knowledgeable in the interpretation of coefficient of
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`variation (CV).
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`4. By experience developing and analyzing products for testing bioequivalence
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`for over 25 years, I am knowledgeable in the interpretation of the 80-125%
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`bioequivalence range.
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`5.
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`I have been asked to review US Patent No. 8,475,832 issued July 2, 2013, and
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`consider the Examples. I have relied solely upon the July 2, 2013 patent in
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`reaching my conclusions.
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`6. Bioequivalence Ranges: Table 2 presents maximum concentration (Cmax) and
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`area under the curve (AUC) data for two Suboxone® tablet doses (2 mg/0.5
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`mg and 16 mg/4 mg of buprenorphine/naloxone, respectively). Table 3
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`presents the acceptable 80%-125% bioequivalence ranges for the same two
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`Suboxone® tablet doses. Tables 2 and 3 both show that Cmax and AUC are
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`dose dependent for buprenorphine and naloxone in that the higher dose Cmax
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`and AUC values for each were 5-6 times higher than the lower dose values.
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`Contrary to the dose-specific data in Table 3, the supporting text following
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`Declaration of Philip T. Lavin, Ph.D.
`US Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`Table 3 states that the drug-specific bioequivalence lower bound is 80% of the
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`lower bound for the lower dose (2 mg/0.5 mg) and the upper bound is 125%
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`of the upper bound for the higher dose (16 mg/2 mg). The broader drug-
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`specific bioequivalence ranges are inconsistent with the traditional
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`bioequivalence, which is dose-specific because, as true for the Suboxone®
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`tablets, the Cmax and AUC of each drug are highly dose dependent. The
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`consequence of the broader drug-specific ranges is to overstate Suboxone®
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`tablet bioequivalence by including ranges that encompass dosages that have
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`Cmax and/or AUC values well outside the dose-specific 80-125%
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`bioequivalence ranges.
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`7. Examples 6, 7, and 8 Suboxone® Sublingual Data Re-use: Examples 6, 7,
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`and 8 each use the identical data (Tmax, Cmax, AUClast, AUCinf, and T1/2) for
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`Suboxone® Sublingual (i.e., Suboxone® tablets) in the related tables. Table 6
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`of Example 6, Table 8 of Example 7, and Table 10 of Example 8 each use the
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`same buprenorphine data for Suboxone® tablets. Similarly, Table 7 of
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`Example 6, Table 9 of Example 7, and Table 11 of Example 8 each use the
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`same naloxone data for Suboxone® tablets. But it is statistically impossible
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`for new experiments to have been conducted and yield identical results for
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`Suboxone® tablets three times in three different comparisons. Contrary to the
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`Declaration of Philip T. Lavin, Ph.D.
`US Patent No. 8,475,832
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`Attorney Docket No. 117744-00041
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`related description, the buprenorphine and naloxone absorption of all three
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`Test Formulations could have been determined in a single in vivo study and
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`the three Examples retrospectively constructed. The statistical impossibility
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`of obtaining identical Suboxone® tablet data undermines the credibility of the
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`comparisons to establish bioequivalence since the Test Formulation data were
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`collected under different experiments according to the explanation in the
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`Examples. This casts doubt on any bioequivalence conclusion based on the
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`data.
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`8. Examples 6-8 Coefficient of Variation Magnitudes: Data Tables 6-11 each
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`contain the CVs for a drug and respective endpoints. It is noted that the
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`Suboxone® tablet buprenorphine CVs range from 24.77% to 46.60% in
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`Tables 6, 8, and 10, and the Suboxone® tablet naloxone CVs range from
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`25.32% to 41.33% in Tables 7, 9, and 11. These CVs are large; typical CVs
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`are in the 10% range. Thus the stated outcomes are unusually variable, which
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`calls into question the confidence in the comparisons with the Test
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`Formulations given the large variation in the endpoints for the control
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`Suboxone® tablets. This further undermines any bioequivalence conclusion
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`based on the data.
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`Declaration of Philip T. Lavin, Ph.D.
`US Patent No. 8,475,832
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`9. Examples 6-8 Naloxone Bioequivalence Data: A visual comparison of the
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`Attorney Docket No. 117744-00041
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`Suboxone® tablet vs. Test Formulations 1, 2 ,and 3 data for the five endpoints
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`(Tmax, Cmax, AUClast, AUCinf and T1/2) in each of Tables 7, 9, and 11 does not
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`support naloxone bioequivalence for any of the Test Formulations. A
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`comparison of the Cmax and AUClast does not support bioequivalence across
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`the Formulations, including the Test Formulation 2 (pH 3-3.5). This point is
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`made twice in the paragraphs following Tables 7 and 9, demonstrated by the
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`data in Tables 7 and 9, and is not much improved for Table 11 where the Cmax
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`does not fall within 80% to 125% of the comparative Suboxone ® tablet
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`value. In short, bioequivalence is consistently not established for the three
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`Test Formulations. This further undermines the any bioequivalence
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`conclusion based on the data.
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`Demaratien :11 Philip T- Lavin, Phi).
`US Patent Ne. 8,4T5,1132
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`Alierney Dfleke1 He.
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`1 lTTttai—tlflflr-ll
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`11].
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`I hereh}I declare that all 51atemen1e inatle herein el‘ my ewe knewledge are
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`true and that all elatemenle made en int'nrmatien and heliet‘ are believed he he
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`true: and further that these etatemente were made with the knewledge that
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`willl'ul talee etatemeam end the like an made are punishahle by fine1 er
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`imprieenmeat, nr 11:51.11, under aeetien [11111 et' Ti1le 13 111' the United States
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`Cede, and that sueh willl'ul etatementa mayjenpardiee the validity of the
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`applieatien at any patents iesuerl thereun.
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`Dated: January 3, 21113
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`Ml-‘l
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`IEMEE'itlm-J
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`Philip T. Lavin PhD, FASA, FRAPS
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`December 31, 2013
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`PHILIP T. LAVIN
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`Founder and Principal
`Lavin Consulting LLC
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`Executive Consultant
`Aptiv Solutions
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`Executive Vice President, Strategic Planning and Innovation Center
`Aptiv Solutions
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`Executive Chairman and Vice Chairman of the Board
`Averion International
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`Founder and Executive Director
`Boston Biostatistics Research Foundation Inc.
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`
`Name:
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`
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`Relevant Experience:
`
`Summary: Over 35 years in public health serving as a biostatistician and executive
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`2013 – Present
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`2013 – Present
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`2011 – 2013
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`2007 – 2011
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`1988 – Present
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`1983 – 2007
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`
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`Responsibilities include:
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`Senior biostatistical consulting, regulatory strategy, and representation for drug, biologics, and device
`approvals and reimbursement.
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`1989-2005
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`
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`Founder and CEO
`Averion International (formerly Boston Biostatistics Inc.)
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`1983-1989
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`1977-1983
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`
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`Adjunct Associate Professor, Clinical Associate Professor
`Harvard Medical School, Boston, MA 02115
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`Associate Professor
`Harvard School of Public Health Boston, MA 02115
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`Assistant Professor
`Harvard School of Public Health Boston, MA 02115
`
`
`Responsibilities included:
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`Teaching, research, and collaborations in pre-clinical studies, clinical trials, longitudinal modeling, meta and mega
`analyses, epidemiology, cost-benefit modeling, and health care reimbursement.
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`Other Academic Experience:
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`1974-1977
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`
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`Research Assistant Professor, Statistical Laboratory,
`Statistical Science Division, SUNY at Buffalo, Buffalo NY
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`Assistant Professor of Research, Division of Applied Mathematics,
`Brown University, Providence RI
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`1972-1974
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`Responsibilities included:
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`Philip T. Lavin PhD, FASA, FRAPS
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`Teaching, research, cooperative group (ECOG, GITSG) collaborations, and publications
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`Education:
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`Brown University, Providence RI
`PhD, Applied Mathematics (Statistics), 1972
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`Presentations:
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`2013
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`2012
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`2011
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`2010
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`2009
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`2008
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`2007
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`2006
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`2005
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`2004
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`2003
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`2002
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`University of Rochester, Rochester NY (Summa Cum Laude)
`AB, Mathematics, 1968
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`
`
`RAPS: Adaptive Designs for Regulatory Submissions
`AdvaMed: Planning Adaptive Studies
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`RAPS: Adaptive Designs for Regulatory Submissions
`RAPS: Maximizing Good Relationships with Regulatory Agencies
`Q1 Productions: Planning and Executing Adaptive Designs
`Q1 Productions: Statistical Strategies for Medical Device Studies
`
`Q1 Productions: Statistical Strategies for Medical Device Studies
`IBC: Reimbursement Planning Strategies using Phase 3 Data
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`IBC: Adaptive Designs for Biologics and Drugs
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`IBC: Statistical Designs for Biomarkers
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`JSM: Quasi-non-inferiority Designs for Medical Devices
`
`Mass BioTech Council: “Statistical Challenges Supporting DMCs”
`Neonatology Summit: “Mortality and LOS Modeling Issues Comparing Surfactants”
`American Statistical Association: “Designing Quasi-superior Device Studies”
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`American Statistical Association: “Common Themes in Medical Device Studies”
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`MassMEDIC: “Designing Combination Studies”
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`Clinical Trials Congress: “Data Monitoring Committees: Making Them Work”
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`New England Business and Technology Association: “Clinical Trials: Speeding
`Drugs to Patients.”
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`7th Annual Clinical Trial Strategies for Medical Devices: “The Three A’s of Data
`Monitoring Committees (DMCs): Administration, Authorization, and Analysis.”
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`
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`Clinical Trials Experience:
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`Drugs:
`AIDS
`Acid Reflux
`Acne
`ARDS
`Asthma
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`Biologics:
`Burns
`Decubitis Ulcers
`Dental Reconstruction
`Huntington’s Disease
`Liver Assist Device
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`Devices:
`Adhesion Prevention (ADCON-L)
`Angina (TMR)
`Biomarkers (CA-125, PSA)
`Breast Cancer Imaging
`Cardiac Adhesions (REPEL-CV)
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`Philip T. Lavin PhD, FASA, FRAPS
`Diabetes
`Multiple Sclerosis
`Endometriosis
`Oncology
`Gastric Ulcers
`Psoriasis
`Hypertension
`Renal Assist Device
`Infection
`Rheumatoid Arthritis
`Lipidemia
`Sepsis
`Motion Sickness
`Transplants
`Nutrition (enteral, obesity)
`Vaccines
`Oncology
`Wound Healing
`Onychomycosis
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`Ophthalmology
`Osteo-arthritis
`Pain Relief
`Pulmonary
`Renal
`Rosacea
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` September 12, 2013
`Cervical Dysplasia Detection
`Cervical Implant (Mobi-C, ProDISC)
`Cryoablation (FROSSTY)
`Dermal Filler (RADIESSE)
`Femoral Artery Closure (VCD)
`Finger Implant (PCP)
`Fracture Healing (SAFHS)
`Hip Implant (C/C)
`Imaging (US, CT, MRI, MGA, SPECT)
`Knee Implant (C/C)
`Knee OA IA (OrthoVisc, Synvisc, SUPARTZ,
`Gel-One)
`Lumbar Impant (ProDISC)
`Metastatic Pain Relief
`Osteoporosis Detection (SAHARA)
`Periodontal Regeneration (GEM21S)
`Rib Spacer (VEPTR)
`Sacral Implant
`Spinal Fusion Cage (BAK)
`Ulcers
`Wound Healing
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` Methodology:
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` Applications:
` Sequential analysis
` Multiple endpoints
` Longitudinal modeling
` Composite endpoints
` Multi-study modeling Exact inference
` Cost-benefit modeling
` Prediction
` Optimization models
` Survival analyses
` Instrument validation
` Time series
` Literature review
` Markov processes
` Cost reimbursement
` Bayes modeling
` Adaptive modeling
` Adaptive design
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`Research Expertise:
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`Clinical :
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`Biomarkers
`Transplantation
`Devices
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`Combination Products
`Oncology
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`Imaging
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`Dermatology
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`Quality of Life
`505(b)2
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`Technical Experience:
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`Software:
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`Honors/Awards:
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`2009
`2008
`2007
`2007-
`2006
`2000
`1999 -
`1985 -
`1984 -
`1981 -
`1976 -
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`MS Word, PowerPoint, Excel, SAS, StatXact, nQuery, EaSt, ADDPLAN
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`RAPS Fellow
`ASA Fellow
`Earl Robinson Award, The American Society of Periodontology
`Who’s Who in the World
`Earl Robinson Award, The American Society of Periodontology
`The American Society of Reproductive Surgery
`Who’s Who in America
`Who’s Who in International Medicine
`Who’s Who in Cancer Research
`Who’s Who in Technology Today
`Who’s Who in American Men of Science
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` September 12, 2013
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`
`Philip T. Lavin PhD, FASA, FRAPS
`National Science Foundation (NSF) Fellowship
`1968 - 1972
`1968
`Phi Beta Kappa
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`Public Service:
`
`1987 – 1993 NASCO, Continuing Education
`1986 – 1997
`Statistical Editor, Antimicrobial Agents and Chemotherapy
`1986 – 1989
`Editorial Board, Drug Information Association (DIA)
`1983 -
`FDA Special Government Employee
`1981 – 1999 NIH Grants and Contracts Reviewer
`
`Affiliations/Memberships:
`
`2013-
`2012-
`2011-
`1986-
`1984-
`1979-
`1976-
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`Publications
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`American Society of Nephrology
`World Molecular Imaging Society
`North American Spine Society
`Regulatory Affairs Professional Society
`Drug Information Association
`Biometrics Society
`American Statistical Association
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`ORIGINAL ARTICLES
`
`
`1. Douglass HO, Jr., Lavin PT. A Study of Nitrosourea Toxicity in Gastrointestinal Protocols of the Eastern
`Cooperative Oncology Group, Cancer Treatment Reports, 60:769-780, 1976.
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`2. Schein P, Lavin P, et al for the Gastrointestinal Tumor Study Group, Randomized Phase II Clinical Trial of
`Adriamycin, Methotrexate, and Actinomycin D, in Advanced Measurable Pancreas Carcinoma, Cancer,
`42:19-22, 1978.
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`3. Falkson G, Moertel C, Lavin P, for the Eastern Cooperative Oncology Group, Chemotherapy Studies in
`Primary Liver Cancer, A Prospective Randomized Clinical Trial, Cancer, 42:2149-2156, 1978.
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`4. Douglass HO, Jr., Lavin PT, et al. for the Eastern Cooperative Oncology Group, Chemotherapy of Advanced
`Measurable Colorectal Cancer, Cancer, 42:2538-2545, 1978.
`
`5. Carbone PP, Davis TE, Zelen M, Lavin P, Eastern Cooperative Oncology Group - Progress Report of
`Activities and Plans, Cancer Clinical Trials, 1:65-75, 1978.
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`6. Schapira D, Hall T, Bennett J, Lavin P, Schnider B, for the Eastern Cooperative Oncology Group, A Phase II
`Study in Estradiol Mustard, Cancer Clinical Trials, 1:5-8, 1978.
`
`7. Chu, TM, Lavin P, Day J, Evans J, Mittelman, A, Holyoke, E, Vincent, R, Carcino-Embryonic Antigen:
`Prognosis and Monitoring of Cancer, Carcino-Embryonic Proteins, Vol. I, Elsevier/North Holland Biomedical
`Press, 1979.
`
`8. Lokich J, Lavin P, Moertel C, et al, for the Gastrointestinal Tumor Study Group, A Multi-Institutional
`Comparative Trial of Radiation Therapy Alone and in Combination with 5-Fluorouracil for Locally
`Unresectable Pancreatic Carcinoma, Annals of Surgery, 189:205-208, 1979.
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` September 12, 2013
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`Philip T. Lavin PhD, FASA, FRAPS
`9. Moertel CG, Engstrom P, Lavin PT, Gelber R, Carbone P, for the Eastern Cooperative Oncology Group, An
`Evaluation of 5-FU, Lactones, and Nitrosoureas in Patients with Advanced Non-Measurable Gastric and
`Pancreas Cancer, Journal of Surgery, 85:509-513, 1979.
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`10. Douglass HO, Lavin PT, Evans J.T, Mittelman A, Carbone PP, Phase II Evaluation of
`Diglycoaldehyde, VP-16-213, and the combination of Methyl-CCNU and Beta-2'-
`Deoxythioguanosine in Previously Treated Patients with Colorectal Cancer: An Eastern Cooperative
`Oncology Group Study (EST-1275), Cancer, 63:1355-1357, 1979.
`
`11. Lavin P, Holyoke D, Zamcheck N, for the Gastrointestinal Tumor Study Group, A CEA
`Standardization Experiment for the Conduct of Multi-institutional Trials, Cancer Treatment Reports,
`63:2031-2033, 1979
`
`
`12. Moertel CG, Lavin PT, for the Eastern Cooperative Oncology Group, Phase II-III Chemotherapy
`Studies in Advanced Gastric Cancer, Cancer Treatment Reports, 63:1863-1869, 1979.
`
`13. Lavin PT, and Moertel CG, for the Gastrointestinal Tumor Study Group, Phase II-III Chemotherapy
`Studies in Advanced Gastric Cancer, Cancer Treatment Reports, 63:1871-1876, 1979.
`
`14. Lokich JJ, Childs DS, Kalser M.H, Lavin PT, Douglass HO, et al, for the Gastrointestinal Tumor
`Study Group: Comparative therapeutic trial of radiation with or without chemotherapy in pancreatic
`carcinoma, Int J Radiat Oncol Biol Phys 5:1643-1647, 1979.
`
`15. Lavin PT, and Flowerdew G, Studies in Variation Associated with the Measurement of Solid Tumors,
`Cancer, 46:1286-1290, 1980.
`
`16. Lavin PT, Mittelman A, Douglass H, Engstrom P, Klaassen D, Survival and Response to
`Chemotherapy of Colorectal Adenocarcinoma, Cancer, 46:1536-1543, 1980.
`
`17. DeWys W, Begg C, Lavin PT, et al, for the Eastern Cooperative Oncology Group, Prognostic Effect
`of Weight Loss Prior to Chemotherapy in Cancer Patients, American Journal of Medicine, 69:491-
`497, 1980.
`
`18. Kinsella TJ, Bloomer W.D, Lavin PT, Knapp RC, Stage II Endometrial Carcinoma: 10 Year
`Followup of Combined Radiation and Surgical Treatment, Gynecologic Oncology, 10:290-297, 1980.
`
`19. Falkson G, Moertel C, MacIntyre J, Lavin P, Engstrom P, Carbone P, The Value of Cytostatic Agents
`in the Treatment of Patients with Primary Liver Cancer, Diagnosis and Treatment of Upper
`Gastrointestinal Tumors, International Congress Series No. 542, 455-459, 1980.
`
`20. Osband M, Lipton J, Lavin P, Levey R, Vawter G, Greenberger J, McCaffrey R, Parkman R,
`Histiocytosis-X: Demonstration of Autoimmunity, Suppressor Cell Deficiency and Successful
`Treatment with Thymic Extract, New England Journal of Medicine, 304:146-153, 1981.
`
`21. Lavin P, Day J, Holyoke ED, Mittelman A, Chu TM, An Evaluation of Baseline and Followup CEA
`in Patients Undergoing Resection for Cure for Colorectal Carcinoma, Cancer, 47:823-826, 1981.
`
`22. Osband M, Shen Y, Shlesinger M, Lavin P, et al, Successful Tumor Immunotherapy with Cimetidine
`in Mice, Lancet, 1:636-638, 1981.
`
`23. Wagoner M, Albert D, Lavin P, Corneal Donor Material Selection, Ophthalmology, 83:139-144,
`1981.
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` September 12, 2013
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`Philip T. Lavin PhD, FASA, FRAPS
`24. Moertel C, Lavin PT, et al, for the Gastrointestinal Tumor Study Group, Therapy of Locally
`Unresectable Pancreatic Carcinoma: A Randomized Comparison of High Dose Radiation Along,
`Moderate Dose Radiation + 5-FU, and High Dose Radiation + 5-FU, Cancer, 48:1705-1710, 1981.
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`25. Lavin P, Alternative Measures of Anti-Tumor Activity in the Evaluation of Solid Tumors, Cancer
`Clinical Trials, 4:451-459, 1981.
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`26. Engstrom P, Lavin P, Douglass HO, Adjuvant Therapy of Gastric Carcinoma using 5-Fluorouracil
`and Semustine, European Journal of Cancer, 31-35, 1981.
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`27. O'Fallon J, Lavin P, O'Connell M, Moertel C, et al, for the Gastrointestinal Tumor Study Group, A
`Comparative Clinical Assessment of Combination Chemotherapy in the Phase II-III Evaluation of
`Combination Therapy with Management of Advanced Gastric Cancer, Cancer, 49:1362-1366, 1982.
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`28. Karp DD, Ervin TJ, Tuttle S, Gorgone B, Lavin PT, Yunis E.J, Pulmonary Complications During
`Granulocyte Transfusions: Incidence and Clinical Features, Vox Sanguinis, 42:57-61, 1982.
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`29. Harmon W, Lavin P, Parkman R, Ingelfinger J, Grupe W, Levey R, The Correlation of Early Acute
`Rejection Episodes with Long-Term Renal Transplant Outcome, Transplantation, 33:648-649, 1982.
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`30. Bruckner H, Lavin P, Plaxe S, Storch JA, Livstone E, for the Gastrointestinal Tumor Study Group,
`Absolute Granulocyte, Lymphocyte, and Monocyte Counts. Useful Determinants of Prognosis for
`Patients with Metastatic Cancer of the Stomach, JAMA, 247:1004-1006, 1982.
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`31. Moertel CG, Lavin PT, Hahn G, Phase II Evaluation of Adriamycin in Islet Cell Carcinoma, Cancer
`Treatment Reports, 66:1567-1569, 1982.
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`32. Harmon W, Parkman R, Lavin P, Grupe W, Ingelfinger J, Yunis E, Levey R, Comparison of Cell
`Medicated Lympholysis and Mixed Lymphocyte Culture in the Immunological Evaluation for Renal
`Transplantation, Transplantation, 129, 4:1573-1577, 1982.
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`33. Lavin PT, Bruckner, H, Plaxe, S, Studies in Prognostic Factors Relating to Chemotherapy for
`Advanced Gastric Cancer, Cancer, 50:2016-2023, 1982.
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`34. Gonder JR, Shields JA, Albert DM, Augsburger JJ, Lavin PT, Uveal Malignant Melanoma
`Associated with Ocular and Oculodermal Melanocytosis, Ophthalmology, 89, 8:953-960, 1982.
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`35. Lavin PT, Structure Preserving Image Restoration, IEEE Pattern Analysis and Machine Intelligence,
`5:14-24, 1983.
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`36. Bruckner H, Lavin P, Plaxe S, Storch JA, Livstone E, for the Gastrointestinal Tumor Study Group,
`Routine Clinical Chemistries as Improved Determinants of Prognosis for Patients with Metastatic
`Cancer of the Stomach, Oncology, 40:31-35, 1983.
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`37. Johnson LA, Lavin P, Moertel CG, et al, Carcinoids: The Association of Histologic Growth Pattern
`and Survival, Cancer, 51:882-889, 1983.
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`38. Bast RC, Reinherz EL, Mayer C, Lavin P, Schlossman SF, Contrasting Effects of Cyclophosphamide
`and Prednisolone on the Phenotype of Human Peripheral Blood Leukocytes, Clinical Immunology
`and Immunopathology, 28:101-114, 1983.
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`39. Lavin PT, Practical Considerations in the Coordination of Clinical Trials, in Issues in the Conduct of
`Clinical Trials, T. Louis and S. Shapiro (Eds.), Marcel Dekker, New York City, 129-153, 1983.
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`40. Albert D, Searl S, Lavin P, Uveal Findings in Patients with Cutaneous Melanoma, American Journal
`of Ophthalmology, 95:474-479, 1983.
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`41. Engstrom, PF, Lavin PT, Klaassen, DJ, Phase II Evaluation of Mitomycin and Cisplatin in Advanced
`Esophageal Carcinoma, Cancer Treatment Reports, 67, 7-8:713-715, 1983.
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`42. Albert DM, Searl SS, Forget B, Lavin PT, Kirkwood J, Nordlund JJ, Uveal profile in patients with
`cutaneous melanoma, Am J Ophthalmol. April;95(4):474-479, 1983.
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`43. Seddon, J, Albert, D, Lavin P, A Prognostic Factor Study of Disease-Free Interval and Survival
`Following Enucleation for Uveal Melanoma, Archives of Ophthalmology, 101:1894-1899, 1983.
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`44. Lavin P, Albert, D, Seddon, J, A Deficit Survival Analysis to Assess the Natural History of Uveal
`Melanoma, Journal of Chronic Diseases, 37, 6:481-487, 1984.
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`45. Engstrom PF, Lavin PT, Moertel CG, Folsch E, Douglass HO, Jr., Streptozotocin plus Fluorouracil
`vs. Doxorubicin Therapy for Metastatic Carcinoid Tumor, Journal of Clinical Oncology, 2, 12:1255-
`1259, 1984.
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`46. Douglass HO, Lavin PT, Goudsmit A, Klaassen DJ, Paul AR, An Eastern Cooperative Oncology
`Group Evaluation of Combinations of Methyl-CCNU, Mitomycin C, Adriamycin and 5-Fluorourail in
`Advanced Measurable Gastric Cancer, Journal of Clinical Oncology, 2, 12:1372-1381, 1984.
`
`47. Bast RC, Klug, TL Schaetzl E, Lavin PT, Niloff J, Greber, T Zurawski, V Knapp, R Monitoring
`Human Ovarian Carcinoma with a Combination of CA-125, CA19-9, and Carcinoembryonic
`Antigen, Obstetrics and Gynecology, 149, 5:553-9, 1984.
`
`48. Williamson JW, Goodenough SH, Liberati A, Patterson WB, Lavin P, Zelen M, Setting Priorities for
`Cancer Control: An Approach, Progress in Clinical and Biological Research, 156:75-86, 1984.
`
`49. Johnson LA, Lavin P, Moertel Wieland L Dayal, Y Doos, WG Geller, SA Cooper, HS Nime, F
`Masse, S Simson, IW Sumner, H Foelsch, E Engstrom, P Carcinoids: The Association of Histologic
`Growth Pattern and Survival, 1984 Year Book of Cancer, R.L. Clark, R.W. Cumley, R.C. Hickey,
`editors. Year Book Medical Publishers, Chicago, 229-230, 1985.
`
`50. Engstrom PF, Lavin PT, Douglass HO, Brunner K.W, Postoperative Adjuvant 5-Fluorouracil plus
`Methyl-CCNU Therapy for Gastric Cancer Patients, Eastern Cooperative Oncology Group Study,
`Cancer, 55:1868-1873, 1985.
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`51. Stoll DB, Lavin PT, Engstrom PF, Hematologic Toxicity of Cisplatin and Mitomycin in Combination
`for Squamous Cell Carcinoma of Esophagus, American Journal of Clinical Oncology, 8:231-234,
`1985.
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`52. Lavin PT, Problems with Tumor Response Criteria, Biology and Treatment of Colorectal Cancer
`Metastasis, Mastromarino, A.(Ed.), Martinus Nijhoff, Boston, 211-224, 1985.
`
`53. Novis BH, Gluck E Thomas P, Steele GD, Zurawski VR, Stewart R, Lavin PT, Zamcheck N, Serial
`Levels of CA 19-9 and CEA in Colonic Cancer, Journal of Clinical Oncology, 4, 6:987-993, 1986.
`
`54. Johnson L, Lavin P, Moertel C, et al, Carcinoids: The Prognostic Effect of Primary Site Histologic
`Type Variations, Primary Site Histoprognostic Type Occurrence Rate Variations, Journal of Surgical
`Oncology, 33:81-83, 1986.
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`55. Niloff JM, Knapp RC, Lavin PT, Malkasian GD, Berek JS, Mortel R, Whitney C, The CA 125 Assay
`as a Predictor of Clinical Recurrence in Epithelial Ovarian Cancer, American Journal of Obstetrics
`and Gynecology, 155:56-60, 1986.
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`56. Berek J, Knapp RC, Malkasian G, Lavin PT, et al, CA 125 Serum Levels Correlate with Second Look
`Operations among Ovarian Cancer Patients, Obstetrics and Gynecology, 67:685-89, 1986.
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`57. Johnson LA, Lavin PT, Dayal YY, Geller SA, Doos WG, Cooper HS, Gerber JE, Masse ST, Weiland
`LH, Moertel CG, et al, Gallbladder Adenocarcinoma: Prognostic Significance of Tumor Acid
`Mucopolysaccharide Content, Journal of Surgical Oncology, 33, 4:243-243, 1986.
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`58. Lavin PT, A Consultant's View of the Draft Guidelines for the Statistical and Clinical Content of the
`New Drug Application, American Statistical Association Proceedings, Biopharmaceutical Section,
`136-138, 1986.
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`59. Johnson LA, Lavin PT, Dayal YY, Geller SA, Doos WG, Cooper HS, Gerber JE, Masse SR, Weiland
`LH, Moertel CG, Engstrom PF, Gallbladder Adenocarcinoma: The Prognostic Significance of
`Histologic Grade, Journal of Surgical Oncology, 34:16-18, 1987.
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`60. Lavin P, Knapp RC, Malkasian G, Whitney CW, Berek JC, Bast RC, CA 125 for the Monitoring of
`Ovarian Carcinoma During Primary Therapy, Obstetrics and Gynecology, 69:223-227, 1987.
`
`61. Kendall K, Mundorf T, Nardin G, Zimmerman TJ, Hesse R, Lavin PT, Tolerability of Timolol and
`Betaxolol in Patients with Chronic Open Angle Glaucoma, Clinical Therapeutics, 9, 6:651-655, 1987.
`
`62. Osband ME, Lavin PT, Rubin LS, Carpinito GA, Hamilton D, Krane RJ, The Correlation of Survival
`with Serum Levels of Interleukin-2 Receptor (IL2-R) and Immunosuppressive Acidic Protein (IAP) in
`Patients with Metastatic Renal Cell Carcinoma Treated with Autolymphocyte Therapy, 1987.
`
`63. Hochberg FH, Lavin PT, Portney R, Roberts D, Tinney C, Hottleman K, Wanger F, Topical Therapy
`of Localized Inflammation in Musicians: A Clinical Evaluation of Aspercreme versus Placebo,
`Medical Problems for Performing Artists, 3, 1:9-14, 1988.
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`64. Kanders BS, Lavin PT, Kowalchuk MB, Greenberg I, Blackburn GL, An Evaluation of the Effect of
`Aspartame on Weight Loss, Appetite, 11, Supplement, 73-84, 1998.
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`65. Chandler B, Lavin PT, Efficacy and Tolerability of Enalapril and Its Effect on Serum Lipids in
`Patients with Mild Uncomplicated Essential Hypertension, Current Therapeutic Research, 43, 6:1143-
`1149, 1988.
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`66. Finkler NJ, Benacerraf B, Lavin PT, Wojciechowski C, Knapp RC, Comparison of CA-125, Clinical
`Impression, and Ultrasound in the Preoperative Evaluation of Ovarian Masses, Obstetrics and
`Gynecology, 72:659-664, 1988.
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`67. Malkasian GD Jr, Knapp RC, Lavin PT, Zurawski VR Jr, Podratz KC, Stanhope CR, Mortel R, Berek
`JS, Bast RC Jr, Ritts RE. Preoperative evaluation of serum CA 125 levels in premenopausal and
`postmenopausal patients with pelvic masses: discrimination of benign from malignant disease. Am J
`Obstet Gynecol. 1988 Aug;159(2):341-6.
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`68. Weir MR, Krichten C, Urick A, Saunders E, Lavin PT. Comparison of enalapril and
`hydrochlorothiazide in mild hypertension and changes in plasma lipid concentrations during therapy”
` Clin Ther. 1988;10(6):712-24.
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`69. Warner KG, Khuri SF, Marston W, Sharma S, Butler MD, Assousa SN, Saad AJ, Soiuffi,SY, Lavin
`PT, Significance of the Transdermal Diminution in Regional Hydrogen Ion Production After
`Repeated Coronary Artery Occlusions, Circulation Research, 64:616-628, 1989.
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`70. Jenison EL, Montag AG, Griffiths CT, Welch WR, Lavin PT, Greer J, Knapp RC, Clear Cell
`Adenocarcinoma of the Ovary: A Clinical Analysis and Comparison with Serous Carcinoma,
`Gynecologic Oncology, 32:65-71, 1989.
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`71. Blackburn GL, Morgan J, Lavin PT, Noble R, Funderburk F, Istfan N, The Determinants of the
`Pressor Effect of Phenylpropanolamine in Healthy Subjects, Journal of the American Medical
`Association, 261:3267-3272, 1989.
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`72. Blackburn GL, Kanders B, Lavin PT, Norton D, Peterson F, The Improvement of Diabetes,
`Hypertension and Cardiovascular Conditions in Obese Subjects Following Very Low Calorie Diets,
`Clinical Nutrition, 1989.
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`73. Kanders BS, Blackburn GL, Lavin PT, Norton D, Weight Loss Outcome and Health Benefits
`Associated with the Optifast Program in the Treatment of Obesity. International Journal of Obesity,
`2, 13:131-134, 1989.
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`74. Wolf BC, Salem RR, Sears HF, Horst DA, Lavin PT, Herlyn M, Itzkowitz SH, Scholm J, Steele, GD,
`Jr, The Expression of Colorectal Carcinoma-Associated Antigens in the Normal Colonic Mucosa. An
`Immunohisto-Chemical Analysis of Regional Distribution, American Journal of Pathology, 135,
`1:111-119, 1989.
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`75. Blackburn GL, Wilson GT, Kanders BS, Stein LJ, Lavin PT, Adler J, Brownell, KD, Weight Cycling:
`The Experience of Human Dieters, American Journal of Clinical Nutrition, 49, 5:1105-1109, 1989.
`
`76. Montag AG, Jenison EL, Griffiths C.T, Welch WR, Lavin PT, Knapp RC, Ovarian Clear Cell
`Carcinoma. A Clinicopathologic Analysis of 44 Cases, International Journal of Gynecological
`Pathology, 8, 2:85-96, 1989.
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`77. Warner KG, Khuri SF, Marston W, Sharma S, Butler, MD, Assousa SN, Saad AJ, Siouffi SY, Lavin
`PT, Significance of the Transmural Dimunution in Regional Hydrogeni