Academic Medical relationship medical Thedemic
between
aca-
centers and the
pharmaceutical industry has recently undergone a significant evolution. Although the full implications remain to be evaluated, the potential synergies of these two researchbased institutions offer possibilities of enhancements in the quality and quantity of applied medical research and
patient care.
See also p 730.
The American Medical Association's Council on Scientific Affairs and Council on Ethical and Judicial Affairs have recently addressed sev-
eral aspects of these relationships.1 Their report points out that industry support for biomedical research has risen sharply, but still represents only 5% of total external funding received by research universities. It further emphasizes that collaborations between medical centers and industry "are fast becoming important to the survival of both industry and academia as the research environment becomes increasingly competitive." The report also enumerates the benefits and risks to clinical investigators, medical centers, and corporations of these collaborations. Sterman,2 from the perspective of the
pharmaceutical industry, empha¬
sizes the mutual benefits to academia and industry. On balance, the ben¬ efits appear to outweigh the risks. Recently, we have seen the salu¬ tary effects of industry/academia col¬ laboration in psychopharmacology as the results of innovative, industrysponsored clinical programs. These collaborations can serve as op¬ timal models of the relationships that could be achieved routinely between both elements. The most elaborate of these collaborations hitherto was the
Center/Industry Collaboration
Cross-National Collaborative Panic Study.3"5 In his overview, Klerman7 describes a number of committees that were established to ensure proper oversight and coordination of collaborations. The industry sponsor and academic investigators agreed on a collaboration that went beyond the requirements for approval of a New Drug Application by the US Food and Drug Administration (required to sat¬ isfy the sponsor's objectives) and ex¬ ceeded the potential of the individual academic centers to generate data from a large sample of patients with a disorder that had been previously studied only on a small scale. Thus, the sponsor's need for a study with a large number of participants pro¬ vided a unique opportunity to ad¬ vance our understanding of a clini¬ cally important disorder. These two activities have traditionally been con¬ ducted independently, the former under pharmaceutical industry spon¬ sorship and the latter under govern¬ ment or other institutional sponsor¬ ship. Surprisingly, use of this obvious synergistic potential did not occur earlier. The Clozaril Collabora¬ tive Study Group6 was involved in a similar multicenter collaboration. The report of the Clomipramine Col¬ laborative Study Group in this issue of the Archives is the most recent of these "marriages." While there are differences, these collaborative pro¬ grams share one feature: by going be¬ yond the basic requirements for ap¬ proval of a new drug by the Food and Drug Administration, the sponsors have provided the academic commu¬ nity with a unique opportunity to conduct, using large numbers of pa¬ tients, "ancillary multicenter stud¬ ies" that do not have a primarily com¬ mercial objective. The clomipramine program was initiated during an investigators' meeting in Boston, Mass, on July 31
Downloaded From: by a Tulane University User on 01/13/2019
and
at which all as¬ two adult clinical trials,
August 1, 1986,
pects of the
including ancillary studies, were dis¬ cussed and planned. This included
training in the use of the then new Yale-Brown Obsessive Compulsive Scale (Y-BOCS).910 Similar to the Cross-National Collaborative Panic Study Group, the Clomipramine Col¬ laborative Study Group faced the challenge of developing new meth¬ ods and testing and validating a new rating scale while testing a new phar¬ macologie treatment for a disorder that had been poorly understood and relatively obscure. Perhaps this inno¬ vative context helped stimulate the additional research initiatives—the ancillary studies. The two adult stud¬ ies described in this issue were com¬ pleted in December 1987. A doubleblind, placebo-controlled study of children and adolescents (aged 10 to 17 years) was initiated later in 1986. These three controlled trials were each followed by 1-year extension tri¬ als. In addition, a humanitarian pro¬ tocol and a treatment protocol under the Food and Drug Administration's new Treatment IND (Investigational New Drug) regulations provided the opportunity for patients who might benefit from clomipramine to receive the drug while it remained under in¬ vestigation. In all, the clinical pro¬ gram treated more than 1500 patients with obsessive-compulsive disorder between 1986 and 1989 (Table). Clo¬ mipramine received approval from the Food and Drug Administration in 1989.
Initially, two senior academic psy¬ investigators (Everett Ellinwood, MD, Duke University, Durham, NC, and Dennis Charney, MD, Yale University, New Haven, chiatric
Conn) were identified as cocoordina-
ancillary studies to the two adult studies. These studies exam¬ ined many facets of obsessivetors of
No. of Patients Duration of Study, wk Study Design 59 239 adults 10 Double-blind, placebo-controlled 61 281 adults 10 Double-blind, placebo-controlled 59E 52 Double-blind, placebo-controlled, extension of protocol 59 85 adults 61E 52 Double-blind, placebo-controlled, extension of protocol 61 127 adults 64 60 children and adolescents 8 Double-blind, placebo-controlled 64A 47 children and adolescents 52 Open-label extension of protocol 64 62 498 adults, adolescents, and children Open-label, humanitarian protocol Open-ended 67 More than 1000 patients treatment Open-label protocol Open-ended *Some patients from protocols 59, 61, 59E, 61E, 64, and 64A continued treatment in protocols 62 and 67. When protocol 67 was initiated, protocol 62 was terminated, and protocol 62 patients continued treatment in protocol 67.
Protocol No.
disorder. The biologic studies included pretreatment and posttreatment cerebrospinal fluid studies, neuroendocrine assess¬ ments, and attempts to correlate plasma levels of clomipramine and active metabolites with clinical out¬
compulsive
Personality studies, family studies, and epidemiologie studies were also undertaken. The opportu¬ nity to conduct this type of research come.
in a large, national sample of patients is an obvious benefit of the industry/
medical center collaboration. Several articles have appeared from the data generated by these multicenter trials. These include a preliminary report11 of the two adult studies that are reported herein in their entirety for the first time; an analysis of secondary efficacy vari¬ ables and long-term data from one of the adult studies and its 1-year, double-blind extension trial1 ; an early report of possible predictors of treatment outcome;13 and three case reports of withdrawal-emergent symptoms.14 The results of the study of children and adolescents will be published soon in the Journal of the American Academy of Child and Adoles¬ cent Psychiatry. Findings of the ancil¬ lary studies also should soon result in several articles. Somberg15 has articulated the need for the publication of data from piv¬ otal efficacy and safety studies and emphasizes the importance of pub¬ lishing results of these multicenter trials in their entirety. While this does not preclude the publication of re¬ sults of individual centers, such re¬ ports should be clearly identified as parts of multicenter programs. The importance of reporting the outcome
of multicenter trials
was
recently
highlighted when a publication from one center participating in a multicenter trial reported conclusions dif¬ ferent from those of the larger anal¬ ysis.16 Fortunately,resultsinfrom the in¬ clomipramine trials, dividual centers agreed with results from the multicenter trials and, in fact, three centers have published their data individually.1 At least some of the intrinsic needs and expectations of both sides can be met collaborative efforts such as the clomipramine, clozapine, and alprazolam projects. These rela¬ tionships, however, can lead to com¬ peting legitimate claims on data— particularly when the area under in¬ vestigation is novel or innovative. In the clomipramine project, this was managed by establishing early in the development of the clinical program an infrastructure for the conduct of ancillary studies and a commitment from the sponsor to: (1) financially support the scientific pursuits de¬ fined in the ancillary studies, (2) share data from the sponsor's da¬ tabase, and (3) relinquish to the in¬ vestigators all control of the conduct of these ancillary studies. In return, the investigators had the usual obli¬
through
gations
to
protect proprietary infor¬
mation and to make data available as required by federal regulations for re¬ porting of investigational new drugs. The multiauthored, study-
group-oriented approach to report¬ ing the safety and efficacy studies re¬
flects the substantial contributions of the investigators and the sponsor, while reports of findings from ancil¬ lary studies will recognize those in¬
vestigators actually participating
Downloaded From: by a Tulane University User on 01/13/2019
in
these
These and the other studies demon¬ collaborative large strate that industry-sponsored, mul¬ ticenter, clinical trials provide oppor¬ tunities to conduct high-quality research of both commercial and ac¬ ademic interest without compromis¬ ing the interests of either party. It is gratifying to be able to recommend this approach to colleagues in aca¬ demia and the pharmaceutical indus¬
try.
projects.
Joseph DeVeaugh-Geiss, MD
CNS Clinical Research Group Glaxo, Inc Five Moore Dr Research Triangle Park, NC 27709 References
1. Council on Scientific Affairs, Council on Ethical and Judicial Affairs. Conflicts of interest in medical center/ industry research relationships. JAMA.
1990;263:2790-2793.
2. Sterman AB. A research edge: new teamwork between industry and academia. Pharm Exec. 1988;8:38-43. 3. Ballenger JC, Burrows GD, DuPont RL Jr, Lesser IM, Noyes R Jr, Pecknold JC, Rifkin A, Swinson RP. Alprazolam in panic disorder and agoraphobia: results from a multicenter trial, I: efficacy in short-term treatment. Arch Gen Psychi-
atry. 1988;45:413-422. 4. Noyes R Jr, DuPont RL Jr, Pecknold JC, Rifkin A, Rubin RT, Swinson RP, Ballenger JC, Burrows GD. Alprazolam in
panic disorder and agoraphobia: results from a multicenter trial, II: patient acceptance, side effects, and safety. Arch Gen
Psychiatry. 1988;45:423-428.
5. Pecknold JC, Swinson RP, Kuch K, Lewis CP. Alprazolam in panic disorder and agoraphobia: results from a multicenter trial, III: discontinuation effects. Arch Gen Psychiatry. 1988;45:429-436. 6. Kane J, Honigfeld G, Singer J, Melt-
zer
H, Clozaril Collaborative Study
Group. Clozapine
for the treatmentresistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789-796. 7. Klerman GL. Overview of the CrossNational Collaborative Panic Study. Arch Gen Psychiatry. 1988;45:407-412. 8. The Clomipramine Collaborative Study Group. Clomipramine in the treatment of patients with obsessivecompulsive disorder. Arch Gen Psychi-
atry. 1991;48:730-738. 9. Goodman WK, Price LH, Rasmussen SA, Masure C, Fleishmann C, Hill C, Heninger G, Charney D. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS), I: development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006-1011. 10. Goodman WK, Price LH, Rasmussen SA, Masure C, Fleishmann C, Hill C, Heninger G, Charney D. The Yale-Brown
Obsessive Compulsive Scale (Y-BOCS), II: validity. Arch Gen Psychiatry. 1989;
46:1012-1016. 11. DeVeaugh-Geiss J, Landau P, Katz R. Treatment of obsessive compulsive
disorder with clomipramine. Psychiatr Ann. 1989;19:97-101. 12. Katz RJ, DeVeaugh-Geiss J, Landau P. Clomipramine in obsessive-compulsive disorder. Biol Psychiatry. 1990; 28:401-414. 13. DeVeaugh-Geiss J, Landau P, Katz R, Goodman W, Rasmussen S. Clinical predictors of treatment response in obsessive compulsive disorder: exploratory analyses from multi-center trials of clomipramine. Psychopharmacol Bull.
1990;26:54-59.
14. Diamond
BI, Borison RL, Katz R,
DeVeaugh-Geiss J. Rebound withdrawal reactions due to clomipramine. Psychopharmacol Bull. 1989;25:209-212. 15. Somberg JC. My data, your data,
whose data? J Clin Pharmacol. 1990; 30:1-2. 16. Jenike MA, Baer L. Correction. Am
Downloaded From: by a Tulane University User on 01/13/2019
J Psychiatry. 1990;147:1393. 17. Jenike MA, Baer L, Summergrad P, Weilberg JB, Holland A, Seymour R. Obsessive
compulsive disorder:
a
double-
blind, placebo-controlled trial of clomipramine in 27 patients. Am J Psychiatry. 1989;146:1328-1330. 18. Greist JH, Jefferson JW, Rosenfeld R, Gutzmann LD, March JS, Barklage NE. and obsessive compuldisorder: a placebo-controlled double-blind study of 32 patients. J Clin
Clomipramine sive
Psychiatry. 1990;51:292-297.
19. Mavissakalian M, Jones B, Olson S, Perel JM. The relationship of plasma clomipramine and N-desmethylclomipramine to response in obsessive-compulsive disorder. Psychopharmacol Bull. 1990;26: 119-122. 20. Mavissakalian MR, Jones B, Olson S. Absence of placebo response in obsessive-compulsive disorder. J Nerv Ment Dis. 1990;178:268-270.
between
aca-
centers and the
pharmaceutical industry has recently undergone a significant evolution. Although the full implications remain to be evaluated, the potential synergies of these two researchbased institutions offer possibilities of enhancements in the quality and quantity of applied medical research and
patient care.
See also p 730.
The American Medical Association's Council on Scientific Affairs and Council on Ethical and Judicial Affairs have recently addressed sev-
eral aspects of these relationships.1 Their report points out that industry support for biomedical research has risen sharply, but still represents only 5% of total external funding received by research universities. It further emphasizes that collaborations between medical centers and industry "are fast becoming important to the survival of both industry and academia as the research environment becomes increasingly competitive." The report also enumerates the benefits and risks to clinical investigators, medical centers, and corporations of these collaborations. Sterman,2 from the perspective of the
pharmaceutical industry, empha¬
sizes the mutual benefits to academia and industry. On balance, the ben¬ efits appear to outweigh the risks. Recently, we have seen the salu¬ tary effects of industry/academia col¬ laboration in psychopharmacology as the results of innovative, industrysponsored clinical programs. These collaborations can serve as op¬ timal models of the relationships that could be achieved routinely between both elements. The most elaborate of these collaborations hitherto was the
Center/Industry Collaboration
Cross-National Collaborative Panic Study.3"5 In his overview, Klerman7 describes a number of committees that were established to ensure proper oversight and coordination of collaborations. The industry sponsor and academic investigators agreed on a collaboration that went beyond the requirements for approval of a New Drug Application by the US Food and Drug Administration (required to sat¬ isfy the sponsor's objectives) and ex¬ ceeded the potential of the individual academic centers to generate data from a large sample of patients with a disorder that had been previously studied only on a small scale. Thus, the sponsor's need for a study with a large number of participants pro¬ vided a unique opportunity to ad¬ vance our understanding of a clini¬ cally important disorder. These two activities have traditionally been con¬ ducted independently, the former under pharmaceutical industry spon¬ sorship and the latter under govern¬ ment or other institutional sponsor¬ ship. Surprisingly, use of this obvious synergistic potential did not occur earlier. The Clozaril Collabora¬ tive Study Group6 was involved in a similar multicenter collaboration. The report of the Clomipramine Col¬ laborative Study Group in this issue of the Archives is the most recent of these "marriages." While there are differences, these collaborative pro¬ grams share one feature: by going be¬ yond the basic requirements for ap¬ proval of a new drug by the Food and Drug Administration, the sponsors have provided the academic commu¬ nity with a unique opportunity to conduct, using large numbers of pa¬ tients, "ancillary multicenter stud¬ ies" that do not have a primarily com¬ mercial objective. The clomipramine program was initiated during an investigators' meeting in Boston, Mass, on July 31
Downloaded From: by a Tulane University User on 01/13/2019
and
at which all as¬ two adult clinical trials,
August 1, 1986,
pects of the
including ancillary studies, were dis¬ cussed and planned. This included
training in the use of the then new Yale-Brown Obsessive Compulsive Scale (Y-BOCS).910 Similar to the Cross-National Collaborative Panic Study Group, the Clomipramine Col¬ laborative Study Group faced the challenge of developing new meth¬ ods and testing and validating a new rating scale while testing a new phar¬ macologie treatment for a disorder that had been poorly understood and relatively obscure. Perhaps this inno¬ vative context helped stimulate the additional research initiatives—the ancillary studies. The two adult stud¬ ies described in this issue were com¬ pleted in December 1987. A doubleblind, placebo-controlled study of children and adolescents (aged 10 to 17 years) was initiated later in 1986. These three controlled trials were each followed by 1-year extension tri¬ als. In addition, a humanitarian pro¬ tocol and a treatment protocol under the Food and Drug Administration's new Treatment IND (Investigational New Drug) regulations provided the opportunity for patients who might benefit from clomipramine to receive the drug while it remained under in¬ vestigation. In all, the clinical pro¬ gram treated more than 1500 patients with obsessive-compulsive disorder between 1986 and 1989 (Table). Clo¬ mipramine received approval from the Food and Drug Administration in 1989.
Initially, two senior academic psy¬ investigators (Everett Ellinwood, MD, Duke University, Durham, NC, and Dennis Charney, MD, Yale University, New Haven, chiatric
Conn) were identified as cocoordina-
ancillary studies to the two adult studies. These studies exam¬ ined many facets of obsessivetors of
No. of Patients Duration of Study, wk Study Design 59 239 adults 10 Double-blind, placebo-controlled 61 281 adults 10 Double-blind, placebo-controlled 59E 52 Double-blind, placebo-controlled, extension of protocol 59 85 adults 61E 52 Double-blind, placebo-controlled, extension of protocol 61 127 adults 64 60 children and adolescents 8 Double-blind, placebo-controlled 64A 47 children and adolescents 52 Open-label extension of protocol 64 62 498 adults, adolescents, and children Open-label, humanitarian protocol Open-ended 67 More than 1000 patients treatment Open-label protocol Open-ended *Some patients from protocols 59, 61, 59E, 61E, 64, and 64A continued treatment in protocols 62 and 67. When protocol 67 was initiated, protocol 62 was terminated, and protocol 62 patients continued treatment in protocol 67.
Protocol No.
disorder. The biologic studies included pretreatment and posttreatment cerebrospinal fluid studies, neuroendocrine assess¬ ments, and attempts to correlate plasma levels of clomipramine and active metabolites with clinical out¬
compulsive
Personality studies, family studies, and epidemiologie studies were also undertaken. The opportu¬ nity to conduct this type of research come.
in a large, national sample of patients is an obvious benefit of the industry/
medical center collaboration. Several articles have appeared from the data generated by these multicenter trials. These include a preliminary report11 of the two adult studies that are reported herein in their entirety for the first time; an analysis of secondary efficacy vari¬ ables and long-term data from one of the adult studies and its 1-year, double-blind extension trial1 ; an early report of possible predictors of treatment outcome;13 and three case reports of withdrawal-emergent symptoms.14 The results of the study of children and adolescents will be published soon in the Journal of the American Academy of Child and Adoles¬ cent Psychiatry. Findings of the ancil¬ lary studies also should soon result in several articles. Somberg15 has articulated the need for the publication of data from piv¬ otal efficacy and safety studies and emphasizes the importance of pub¬ lishing results of these multicenter trials in their entirety. While this does not preclude the publication of re¬ sults of individual centers, such re¬ ports should be clearly identified as parts of multicenter programs. The importance of reporting the outcome
of multicenter trials
was
recently
highlighted when a publication from one center participating in a multicenter trial reported conclusions dif¬ ferent from those of the larger anal¬ ysis.16 Fortunately,resultsinfrom the in¬ clomipramine trials, dividual centers agreed with results from the multicenter trials and, in fact, three centers have published their data individually.1 At least some of the intrinsic needs and expectations of both sides can be met collaborative efforts such as the clomipramine, clozapine, and alprazolam projects. These rela¬ tionships, however, can lead to com¬ peting legitimate claims on data— particularly when the area under in¬ vestigation is novel or innovative. In the clomipramine project, this was managed by establishing early in the development of the clinical program an infrastructure for the conduct of ancillary studies and a commitment from the sponsor to: (1) financially support the scientific pursuits de¬ fined in the ancillary studies, (2) share data from the sponsor's da¬ tabase, and (3) relinquish to the in¬ vestigators all control of the conduct of these ancillary studies. In return, the investigators had the usual obli¬
through
gations
to
protect proprietary infor¬
mation and to make data available as required by federal regulations for re¬ porting of investigational new drugs. The multiauthored, study-
group-oriented approach to report¬ ing the safety and efficacy studies re¬
flects the substantial contributions of the investigators and the sponsor, while reports of findings from ancil¬ lary studies will recognize those in¬
vestigators actually participating
Downloaded From: by a Tulane University User on 01/13/2019
in
these
These and the other studies demon¬ collaborative large strate that industry-sponsored, mul¬ ticenter, clinical trials provide oppor¬ tunities to conduct high-quality research of both commercial and ac¬ ademic interest without compromis¬ ing the interests of either party. It is gratifying to be able to recommend this approach to colleagues in aca¬ demia and the pharmaceutical indus¬
try.
projects.
Joseph DeVeaugh-Geiss, MD
CNS Clinical Research Group Glaxo, Inc Five Moore Dr Research Triangle Park, NC 27709 References
1. Council on Scientific Affairs, Council on Ethical and Judicial Affairs. Conflicts of interest in medical center/ industry research relationships. JAMA.
1990;263:2790-2793.
2. Sterman AB. A research edge: new teamwork between industry and academia. Pharm Exec. 1988;8:38-43. 3. Ballenger JC, Burrows GD, DuPont RL Jr, Lesser IM, Noyes R Jr, Pecknold JC, Rifkin A, Swinson RP. Alprazolam in panic disorder and agoraphobia: results from a multicenter trial, I: efficacy in short-term treatment. Arch Gen Psychi-
atry. 1988;45:413-422. 4. Noyes R Jr, DuPont RL Jr, Pecknold JC, Rifkin A, Rubin RT, Swinson RP, Ballenger JC, Burrows GD. Alprazolam in
panic disorder and agoraphobia: results from a multicenter trial, II: patient acceptance, side effects, and safety. Arch Gen
Psychiatry. 1988;45:423-428.
5. Pecknold JC, Swinson RP, Kuch K, Lewis CP. Alprazolam in panic disorder and agoraphobia: results from a multicenter trial, III: discontinuation effects. Arch Gen Psychiatry. 1988;45:429-436. 6. Kane J, Honigfeld G, Singer J, Melt-
zer
H, Clozaril Collaborative Study
Group. Clozapine
for the treatmentresistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789-796. 7. Klerman GL. Overview of the CrossNational Collaborative Panic Study. Arch Gen Psychiatry. 1988;45:407-412. 8. The Clomipramine Collaborative Study Group. Clomipramine in the treatment of patients with obsessivecompulsive disorder. Arch Gen Psychi-
atry. 1991;48:730-738. 9. Goodman WK, Price LH, Rasmussen SA, Masure C, Fleishmann C, Hill C, Heninger G, Charney D. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS), I: development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006-1011. 10. Goodman WK, Price LH, Rasmussen SA, Masure C, Fleishmann C, Hill C, Heninger G, Charney D. The Yale-Brown
Obsessive Compulsive Scale (Y-BOCS), II: validity. Arch Gen Psychiatry. 1989;
46:1012-1016. 11. DeVeaugh-Geiss J, Landau P, Katz R. Treatment of obsessive compulsive
disorder with clomipramine. Psychiatr Ann. 1989;19:97-101. 12. Katz RJ, DeVeaugh-Geiss J, Landau P. Clomipramine in obsessive-compulsive disorder. Biol Psychiatry. 1990; 28:401-414. 13. DeVeaugh-Geiss J, Landau P, Katz R, Goodman W, Rasmussen S. Clinical predictors of treatment response in obsessive compulsive disorder: exploratory analyses from multi-center trials of clomipramine. Psychopharmacol Bull.
1990;26:54-59.
14. Diamond
BI, Borison RL, Katz R,
DeVeaugh-Geiss J. Rebound withdrawal reactions due to clomipramine. Psychopharmacol Bull. 1989;25:209-212. 15. Somberg JC. My data, your data,
whose data? J Clin Pharmacol. 1990; 30:1-2. 16. Jenike MA, Baer L. Correction. Am
Downloaded From: by a Tulane University User on 01/13/2019
J Psychiatry. 1990;147:1393. 17. Jenike MA, Baer L, Summergrad P, Weilberg JB, Holland A, Seymour R. Obsessive
compulsive disorder:
a
double-
blind, placebo-controlled trial of clomipramine in 27 patients. Am J Psychiatry. 1989;146:1328-1330. 18. Greist JH, Jefferson JW, Rosenfeld R, Gutzmann LD, March JS, Barklage NE. and obsessive compuldisorder: a placebo-controlled double-blind study of 32 patients. J Clin
Clomipramine sive
Psychiatry. 1990;51:292-297.
19. Mavissakalian M, Jones B, Olson S, Perel JM. The relationship of plasma clomipramine and N-desmethylclomipramine to response in obsessive-compulsive disorder. Psychopharmacol Bull. 1990;26: 119-122. 20. Mavissakalian MR, Jones B, Olson S. Absence of placebo response in obsessive-compulsive disorder. J Nerv Ment Dis. 1990;178:268-270.
