Comments on: ‘Salami Slicing’ Promoted Lilly’s Cymbalta: Study

By: M Helm, MD

M Helm, MD — Thu, 07 Jan 2010 03:52:56 +0000

RD50,

There is a distinction between pooling disparate datasets to generate “new” (and positive) findings for publication and a very large study with intensive data collection designed from the start to generate answers to a large number of specific research questions. There are also problems with reporting “post-hoc” and subgroup analyses when the studies are not designed to accurately assess the question they purport to answer.

CATIE (and several other NIH funded studies) did indeed generate a large number of publications. However, these studies had specific arms within them which were designed to answer these questions. This is a very different approach. The listing of 41 published reports from the CATIE study overstates the actual original findings of the research. Your listing includes commentaries, reviews, and editorials.

I find it particularly annoying when a (typically industry-funded study of a single drug) fails to prove a difference on a primary outcome, but the write-up (and often future studies) focus more on a secondary outcome where a difference was shown. Also annoying are studies which focus on measures that are abstractions of the desired treatment effect/outcome. For example using the antipsychotics - It is not useful to demonstrate a reduction in the number of hallucinations per day, but a desirable outcome would be reduction in need for in-patient treatment or reduction in medication related complications.

By: Jack Friday

Jack Friday — Thu, 07 Jan 2010 03:00:17 +0000

Salami-ing the data from studies only occurs in the industry when the results point in the “right direction”!

Negative studied are “salted away”!

By: RockDoc50

RockDoc50 — Wed, 06 Jan 2010 21:29:32 +0000

Here is a list of 41 (up to Mar 2007) publications generated from a single NIMH-funded study, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). There was no pharmaceutical industry sponsorship or influence on this trial. I don’t know how many additional articles have been published since Mar ‘07 on the CATIE study. These articles are generated from the same data set.

I think the article should have been more fair-balanced about “salami slicing”–it obviously doesn’t only occur with industry sponsored studies.

Published papers for the Schizophrenia Trial
Updated March 26, 2007

Stroup, TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Capuano G, Rosenheck
RA, Keefe RSE, Miller A, Belz I, Hsiao JK for the CATIE Investigators. (2007)
Effectiveness of Olanzapine, Quetiapine, and Risperidone in Patients with
Chronic Schizophrenia after Discontinuing Perphenazine: A CATIE Study.
American Journal of Psychiatry, 164, 415-427.

Swartz MS, Perkins DO, Stroup TS, Davis SM, Capuano G, Rosenheck RA, Reimherr F,
McGee MF, Keefe RSE, McEvoy JP, Hsiao JK, Lieberman JA for the CATIE
Investigators. (2007) Effects of antipsychotic medications on psychosocial
functioning in patients with chronic schizophrenia: Findings from the NIMH
CATIE Study. American Journal of Psychiatry, 164, 428-436.

Sullivan PF, Keefe RS, Lange LA, Lange EM, Stroup TS, Lieberman J, Maness PF.
(2007) NCAM1 and neurocognition in schizophrenia. Biological Psychiatry, 61(7),
902-10.

Rosenheck RA, Leslie DL, Sindelar J, Miller EA, Lin H, Stroup TS, McEvoy J, Davis SM,
Keefe RSE, Swartz M, Perkins DO, Hsiao JK, Lieberman J for the CATIE Study
Investigators. (2006) Cost-Effectiveness of Second Generation Antipsychotics
and Perphenazine in a Randomized Trial of Treatment for Chronic
Schizophrenia. American Journal of Psychiatry, 163, 2080-2089.

Essock SM, Covell NH, Davis SM, Stroup TS, Rosenheck RA, Lieberman JA. (2006)
Effectiveness of Switching Antipsychotic Medications. American Journal of
Psychiatry, 163, 2090-2095.

Lieberman JA. (2006) Comparative Effectiveness of Antipsychotic Drugs: A Commentary
on Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study
(CUtLASS 1) and Clinical Antipsychotic Trials of Intervention Effectiveness
(CATIE). Archives of General Psychiatry, 63(10),1069-72.

Citrome L, Stroup TS. (2006) Schizophrenia, Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE) and number needed to treat: how can CATIE inform
clinicians? International Journal of Clinical Practice, 60(8), 933-40.

Lieberman JA, Hsiao JK. (2006) Interpreting the Results of the CATIE Study. Psychiatric
Services, 57(8), 139.

Lieberman JA. (2006) What the CATIE Study Means for Clinical Practice. Commentary.
Psychiatric Services, 57(8), 1075.

Rosenheck RA, Swartz MS, Lieberman JA. (2006) Introduction to the Special Section on
CATIE Baseline Data: Practical Clinical Trials in Psychiatry: Studies of
Schizophrenia From the CATIE Network. Psychiatric Services, 57(8), 1093.
2

Chakos MH, Glick ID, Miller AL, Hamner MB, Miller DD, Patel JK, Tapp A, Keefe RSE,
Rosenheck RA. (2006) Baseline Use of Concomitant Psychotropic Medications
to Treat Schizophrenia in the CATIE Trial. Psychiatric Services, 57(8), 1094-101.

Chwastiak LA, Rosenheck RA, McEvoy JP, Keefe RS, Swartz MS, Lieberman JA.
(2006) Interrelationships of Psychiatric Symptom Severity, Medical Comorbidity,
and Functioning in Schizophrenia. Psychiatric Services, 57(8),1102-9.

Swartz MS, Wagner HR, Swanson JW, Stroup TS, McEvoy JP, McGee M, Miller DD,
Reimherr F, Khan A, Canive JM, Lieberman JA. (2006) Substance Use and
Psychosocial Functioning in Schizophrenia Among New Enrollees in the NIMH
CATIE Study. Psychiatric Services, 57(8),1110-6.

Perlick DA, Rosenheck RA, Kaczynski R, Swartz MS, Canive JM, Lieberman JA. (2006)
Components and correlates of family burden in schizophrenia. Psychiatric
Services, 57(8), 1117-25.

McEvoy JP. (2006) Introduction: An Overview of the Clinical Antipsychotic Trials of
Intervention Effectiveness (CATIE) Study. CNS Spectrums, 11(7 Suppl 7), 4-8.

Perkins DO. (2006) Clinical trials in schizophrenia with results for the real world.
CNS Spectrums, 11(7 Suppl 7), 9-13.

Meltzer HY, Bobo WV. (2006) Interpreting the Efficacy Findings in the CATIE Study:
What Clinicians Should Know. CNS Spectrums, 11 (7 Suppl 7), 14-24.

Nasrallah HA, Meyer JM, Goff DC, McEvoy JP, Davis SM, Stroup TS. (2006) Low Rates
of Treatment for Hypertension, Dyslipidemia and Diabetes in Schizophrenia:
Data from the CATIE Schizophrenia Trial Sample at Baseline. Schizophrenia
Research, 86(1-3), 15-22.

Swanson J, Swartz M, van Dorn Richard, Elbogen E, Wagner R, Rosenheck R, Stroup
S, McEvoy K, Lieberman J. (2006) A National Study of Violent Behavior in
Persons with Schizophrenia. Archives of General Psychiatry, 63, 490-499.

Keefe RS, Bilder RM, Harvey PD, Davis SM, Palmer BW, Gold JM, Meltzer HY, Green
MF, Miller DD, Canive JM, Adler LW, Manschreck TC, Swartz M, Rosenheck R,
Perkins DO, Walker TM, Stroup TS, McEvoy JP, Lieberman JA. (2006) Baseline
Neurocognitive Deficits in the CATIE Schizophrenia Trial.
Neuropsychopharmacology. 31(9), 2033-46.

McEvoy JP, Lieberman JA, Stroup TS, Davis SM, Rosenheck RA, Swartz MS, Perkins
DO, Keefe RSE, Davis CE, Severe J, Hsiao JK for CATIE Investigators. (2006)
Effectiveness of clozapine versus olanzapine, quetiapine and risperidone in
patients with chronic schizophrenia who did not respond to prior atypical
antipsychotic treatment. American Journal of Psychiatry, 163, 600-610.

Stroup TS, Lieberman JA, McEvoy JP, Swartz MS, Davis SM, Rosenheck RA, Perkins
DO, Keefe RSE, Davis CE, Severe J, Hsiao JK for the CATIE Investigators.
(2006) Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in
patients with chronic schizophrenia after discontinuing a previous atypical
antipsychotic. American Journal of Psychiatry, 163, 611-622.

Rosenheck R, Leslie D, Keefe R, McEvoy J, Swartz M, Perkins D, Stroup S, Hsiao JK,
Lieberman J. (2006) Barriers to employment for people with schizophrenia.
American Journal of Psychiatry, 163(3), 411-7.
3

Swartz MS, Wagner HR, Swanson JW, Stroup TS, McEvoy JP, Canive JM, Miller DD,
Reimherr F, McGee M, Kahn A, Van Dorn R, Rosenheck RA, Lieberman JA.
(2006) Substance use in persons with schizophrenia: Baseline prevalence and
correlates from the NIMH CATIE study. The Journal of Nervous and Mental
Disease, 194(3), 164-72.

Stroup TS, Appelbaum PS. (2006) Evaluation of “Subject Advocate” Procedures in the
Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia
Study. Schizophrenia Bulletin, 32(1), 147-52.

Goff DC, Sullivan LM, McEvoy JP, Meyer JM, Nasrallah HA, Daumit GL, Lamberti S,
D’Agostino RB, Stroup TS, Davis S, Lieberman JA. (2005) A comparison of tenyear
cardiac risk estimates in schizophrenia patients from the CATIE study and
matched controls. Schizophrenia Research, 80, 45-53.

Keefe R, Bilder RM, Harvey PD, Davis S, Palmer B, McEvoy JP, Goldberg TE, Gold JM,
Green MF, Swartz M, Stroup S, Rosenheck R, Perkins DO, Meltzer HY, Miller D,
Canive J, Walker TM, Lieberman JA. (2005) Baseline neurocognitive assessment
of 1364 patients with schizophrenia in the clinical antipsychotic trials for
intervention effectiveness (CATIE) project. Schizophrenia Bulletin, 31(2), 361-
362.

Keefe R, Bilder RM, Palmer B, Harvey PD, Davis S, McEvoy J, Goldberg TE, Gold J,
Green MF, Swartz M, Stroup S, Rosenheck R, Perkins D, Meltzer H, Lieberman
JA. (2005) Baseline neurocognitive assessment of 1364 patients with
schizophrenia in the clinical antipsychotic trials for intervention effectiveness
(CATIE) project. Biological Psychiatry, 57(8), 79S-79S.

Lieberman J, Stroup TS, McEvoy J, Swartz M, Rosenheck R, Perkins DO, Keefe RSE,
Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK. (2005) Effectiveness of
antipsychotic drugs in patients with chronic schizophrenia. New England Journal
of Medicine, 353(12), 1209-1223.

McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L, Meltzer HY, Hsiao
J, Scott ST, Lieberman JA. (2005) Prevalence of the metabolic syndrome in
patients with schizophrenia: Baseline results from the Clinical Antipsychotic Trials
of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with
national estimates from NHANES III. Schizophrenia Research, 80, 19-32.

Meyer JM, Nasrallah HA, McEvoy JP, Goff DC, Davis SM, Chakos M, Patel JK, Keefe
RS, Stroup TS, Lieberman JA. (2005) The Clinical Antipsychotic Trials of
Intervention Effectiveness (CATIE) Schizophrenia Trial: Clinical comparison of
subgroups with and without the metabolic syndrome. Schizophrenia Research,
80, 9-18.

Miller D, McEvoy JP, Davis SM, Caroff SN, Saltz BL, Chakos MH, Swartz MS, Keefe
RS, Rosenheck RA, Stroup TS, Lieberman JA. (2005) Clinical correlates of
tardive dyskinesia in schizophrenia: Baseline data from the CATIE schizophrenia
trial. Schizophrenia Research, 80, 33-43.

Rosenheck RA, Stroup S, Keefe R, McEvoy J, Swartz M, Perkins D, Hsiao J, Shumway
M, Lieberman J. (2005) Measuring outcome priorities and incorporating
preferences in mental health status assessment of people with schizophrenia.
British Journal of Psychiatry, 187, 529-536.
4

Stroup S, Appelbaum P, Swartz M, Patel M, Davis S, Jeste D, Kim S, Keefe R,
Manschreck T, McEvoy J, Lieberman J. (2005) Decision-making capacity for
research participation among individuals in the CATIE schizophrenia trial.
Schizophrenia Research, 80, 1-8.

Sernyak MJ, Leslie D, Rosenheck, R. (2003). Use of system-wide outcomes monitoring
data to compare the effectiveness of atypical neuroleptic medications. American
Journal of Psychiatry, 160(2), 310-315.

Lieberman JA, Stroup TS. (2003). Guest editors’ introduction: what can large pragmatic
clinical trials do for public mental health care? Schizophrenia Bulletin, 29(1), 1-6.

Stroup TS, McEvoy JP, Swartz MS, Byerly MJ, Glick ID, Canive JM, McGee MF,
Simpson GM, Stevens MC, Lieberman JA. (2003). The National Institute of
Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)
project: schizophrenia trial design and protocol development. Schizophrenia
Bulletin, 29(1),15-31.

Swartz MS, Perkins DO, Stroup TS, McEvoy JP, Nieri JM, Haak DC. (2003). Assessing
clinical and functional outcomes in the Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE) schizophrenia trial. Schizophrenia Bulletin, 29(1), 33-43.

Keefe RS, Mohs RC, Bilder RM, Harvey PD, Green MF, Meltzer HY., et al. (2003).
Neurocognitive assessment in the Clinical Antipsychotic Trials of Intervention
Effectiveness (CATIE) project schizophrenia trial: development, methodology,
and rationale. Schizophrenia Bulletin, 29(1), 45-55.

Davis SM, Koch GG, Davis CE, LaVange LM. (2003) Statistical approaches to
effectiveness measurement and outcome-driven re-randomizations in the Clinical
Antipsychotic Trials of Intervention Effectiveness (CATIE) studies. Schizophrenia
Bulletin, 29(1), 73-80.

Rosenheck R, Doyle J, Leslie D, Fontana A. (2003). Changing environments and
alternative perspectives in evaluating the cost-

By: Santa

Santa — Wed, 06 Jan 2010 21:11:18 +0000

Hi elmore,
Don’t you think that labeling and pub planning are part of the same process? A pub plan is intended to prepare the way for the drug’s launch and beyond; if the messages developed and disseminated aren’t in sync with labeling it’s not very useful. A pub plan should be developed with target attributes in mind. Once they are then both activities should run in parallel. I’m saying that salami slicing isn’t the basis for pub planning, but it can be a legitimate part of the way it is used tactically.

By: elmore

elmore — Wed, 06 Jan 2010 20:37:12 +0000

Santa: Sorry, but in my experience identifying the major attributes of a drug, etc is part of labeling, not pubs. And what you call irrelevant-how many times the data are used and in what ways-is exactly what salami slicing is all about.

By: Santa

Santa — Wed, 06 Jan 2010 18:40:48 +0000

It is not the basis for pub plans. The basis for pub plans is to identify the major attributes of a drug, clarify for which conditions it is best suited, highlight the ways in which it should be used, and develop ways to communicate that to practitioners who will be involved in its use. A pub plan is credible only when those messages are supportable and supported by data. How many times the data are used and in what ways is irrelevant, and less important than ensuring that practitioners are aware of the potential uses of the drug. A pub plan is a structured way to disseminate messages about a drug to its users and makes most use of available data.

By: elmore

elmore — Wed, 06 Jan 2010 14:45:25 +0000

Salami slicing is the basis for pub plans.

By: DRW

DRW — Wed, 06 Jan 2010 14:37:56 +0000

I don’t agree with the suggestion that multiple publications (each examining a different hypothesis) from the same underlying data set is such a bad thing. After all, a significant amount of patient and physician time goes into generating the data. If we can credibly draw more than one conclusion from that data then why not??

If the analytical methods used on the data are sound, and the results of the analysis could potentially further public health, then I say publish.

DRW