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Interim Report
INTERIM REPORT
Drug Interactions Pilot Project*
Evaluations of Drug
Interactions
American Pharmaceutical Association
By L. Luan Corrigant
growing concern relative to the . problem of drug interactions developed within the profession in the late 1960's. This concern was vocalized by a number of professionals; within the APhA Academy of General Practice of Pharmacy, members urged the development by APhA of a compendium of drug interactions. During this period of developing interest and concern, a number of reviews and compilations were prepared and published by various individuals and organizations. It was generally felt, however, that these compilations did not really meet the requirements and desires of the practicing pharmacist. As elaborated by AGP members, the practitioner needed concise information relative to drug interactions and, at the same time, this information had to be comprehensive enough to allow the practitioner to arrive at intelligent judgments concerning various drug therapies.
A
Evolution of Pilot Project It was noted that the available compilations generally tended simply to abstract the literature without attempting to evaluate it, producing a situation in which one article might be published on a particular interaction,
0 This report will summarize the various activities of the APhA Drug Interactions Pilot Project and will elaborate on some of the decisions that went into the development and publication of the pilot version of "Evaluations of Drug Int eractions." The pilot project was directed by Edward G. F e.ldm_ann, APhA associate executive director for sctenttfic affairs, with Richard P. Penna, secretary of the Academy of General Practice of Pharmacy, as project advisor.
t Miss Corrigan is an administrative assistant in the. APhA Scientific Division. She was a project ass!stant in the pilot study and is the technical edttor of the prototype version of "Evaluations of Drug Interactions."
200
abstracted in another and then cited in another. Finally, all three might show up in another article as three separate pieces of evidence for the alleged interaction. It was recognized early in the Drug Interactions Pilot Project that a review process analogous to that employed by the American Dental Association's Council on Dental Therapeutics, the American Medical Association's Council on Drugs, the NF Admissions Committee and the USP Subcommittee on Scope has general acceptance by the professions. It was felt that a review process such as this could cut through the confusion of the drug interactions literature and aid in arriving at authoritative, consensus opinions. The resolution developed by the APhA Committee on Professional Affairs and passed by the APhA House of Delegates at the 1970 annual meeting called on APhA to "initiate a comprehensive study to make available to pharmacists information on drug interactions. Attention should be given to making this information available in a concise form which will include an explanation of the mechanism and clinical significance of specific drug interactions." To fulfill the directives within the resolution, it was necessary to study and evaluate the area of drug interactions for a better understanding of how best to deal with the problem. To achieve a clearer delineation of this problem area, a feasibility study was conducted by the APhA scientific division, under the direction of Edward G. Feldmann, associate executive director for scientific affairs. The report on the feasibility study made to the Board of Trustees in June 1970 indicated that the data collected for the study bore out previous indications that there was a need for a comprehensive and authoritative com-
Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION
pendium on drug interactions. Because of uncertainty relative to just how to approach the development of a new compendium and how to present the information for the most efficient use by the typical practitioner, the Board voted to proceed by way of the pilot project. A pilot project, climaxed by the publication of a prototype of the anticipated compendium, would fulfill several necessary functions. First, it would establish if the envisioned review process would indeed result in useful and applicable information for the practitioner. Second, it would provide an opportunity to work out various production and layout problems that would affect the projected compilation. Third, it would allow for a thorough review of an actual product by a representative sampling of the membership and by other interested parties. Although operating under a rigorous schedule, it was felt that the prototype publication could be available for limited distribution at the 1971 annual meeting in San Francisco. Having the prototype available for distribution at the annual meeting would in itself provide .much initial feedback concerning its suitability. As additional opportunities for feedback, Dr. Feldmann spoke before meetings of pharmacy practitioners in San Francisco. Because the publication of the prototype was undertaken literally on a crash basis, it was impossible to provide all those in attendance at the annual meeting with copies. However, it was essential that the opinions of the membership about the prototype be adequately assessed, since the compilation was to be prepared for their use. To determine the response of the membership, a random selection of several thousand members was made from the association's membership ros-
ter; the mailing of review copies to this sampling was begun shortly after the annual meeting. A questionnaire covering basic aspects of the prototype was included in the booklet to facilitate response by those who reviewed and evaluated the prototype. Development of Prototype The prototype, "Evaluations of Drug Interactions (EDI) ," is a seventy-page booklet that contains representative drug interactions and related topics prepared by the participants of the Drug Interactions Pilot Project. The prototype includes the one-page questionnaire and four distinct sections, each section printed on a different color of paper for rapid identification. The four sections are -front matter (which includes the preface and introduction), monographs, chapters and index. The index is a key feature of the publication, designed to provide rapid access to the desired information. From the very early stages of the project, a review process similar to those already enumerated was conceived to be an essential part of the compilation. Hence, it was deemed necessary to utilize two distinct, but complementary, panels-a Review Panel, which would be responsible for compiling, reviewing and evaluating the literature on a specific drug interaction; and a Practitioner Panel, which would be responsible for determining the usefulness of the compiled information to the practitioner as well as the actual means of presenting that information for his most efficient use. While there already existed a substantial number of articles in the literature about drug interactions, the Practitioner Panel had to determine how this information should be divided or cataloged for use by the practitioner. ft was obvious that a certain amount of information was essential; the question became where to draw the line. How much information did the practitioner need to reach an intelligent judgment? How could the compilation be both concise and comprehensive? The Practitioner Panel suggested that the monographs should contain enough information to provide the practitioner with a firm base on which to make his decisions. The actual hows and whys of drug interactions should be provided, though not necessarily in the monographs. Hence, the concept of each monograph containing essentially the same If additional elements developed. background information would be helpful and necessary to understand the interaction discussed in the mono-
graphs, it would be included in a chapter. Therefore, with the aid of the Practitioner Panel, the pilot project members developed the following basic format for the monographsTitle-if sufficient information is known about the mechanism of the interaction, the first drug given in the title is the drug that is acted upon in the interaction, and the second drug mentioned is the drug that produces the interaction.
information I. Summary-includes concerning the clinical significance of the interaction as well as indicating some course of action. II. Related Drugs-gives the names of related drugs or drugs that might be expected to act in a similar manner. III. Pharmacological Effect and Mechanism-discusses some of the background information needed to understand why the interaction occurs and what its effects might be. IV. Evaluation of Clinical Data-summarizes the most significant studies or the most pertinent studies pertaining to the interaction. V. Clinical Significance-gives the relative significance of the interaction in practice. VI. Recommend a ti o ns-i ncludes courses of action, such as changes or adjustments in dosage or dosage forms as well as indicating the need for certain laboratory tests or other methods of surveillance.
VII. References-provides substantiation for data leading to the evaluations presented in the monographs. Nonproprietary and trade names of drugs are provided at the end of each monograph, set off in a box for quick location. While defining the scope of the monographs proceeded rather smoothly, delineating the material to be contained in the chapters proved more complex. The style or format of ~he chapters could not be so easily designated. When moving from a specific drug-drug interaction to an explanation of the phenomenon, quite a few variables are introduced, such as the state of knowledge concerning the particular disease condition, the number of alternate therapies, and the inherent nature of a particular class of drugs. It should be realized that if and when a complete compendium is prepared, the material in the chapters will undoubtedly be refined and the chapters made more consistent; however, the nature of the material and the intent of the chapters to provide additional and supplemental information preclude a totally consistent format and length. For the purposes of the prototype, the selection of the drug-drug interactions to be included was based on an attempt to provide a representative sampling of interactions, rather than an attempt to take the ten most well-documented interactions or the ten most serious interactions. By tak-
Review Panel Members William H. Barr, PharmD, PhD, assistant professor of pharmaceutics, State University of New York at Buffalo Edward A. Hartshorn, PhD, director of pharmacy services, Evanston Hospital, Evanston, Illinois Daniel A. Hussar, PhD, associate professor of pharmacy, Philadelphia College of Science and Pharmacy Robert E. Pearson, MS, project coordinator, Michigan Regional Drug Information Network, University Hospital, Ann Arbor, Michigan Fred J. Salter, PharmD, acting assistant director, Clinical Pharmacy Services, Medical College of Virginia Hospitals, Richmond James A. Visconti, PhD, assistant professor of pharmacy, director of Drug Information Center, Ohio State University, Columbus
Practitioner Panel Members Ernest H. Luther, BS, hospital pharmacist, Doctors Hospital Pharmacy, Inc., Fairfax, Virginia William E. Merritt, BS, community pharmacist, Johnson's Pharmacy, Greenville, Delaware William H. Randall, BS, community pharmacist, LaFayette Drug Company, Lillington, North Carolina Byron C. Spoon Jr., BS, community pharmacist, The Peoples Drug Company, Dayton, Ohio
Vol. NSll, No. 4, April 1971
201
ing this approach, it was hoped that a better picture of the proposed compendium would be provided. The interactions, therefore, in the prototype range from those that are recognized and documented to be clinically significant to some that have been alleged to be serious but are actually without foundation in the literature or in practice. The selection of the topics to be developed in the chapters was not quite so easily made. It was acknowledged that in the final compilation not every monograph would have a chapter; indeed, one chapter often would encompass the interactions presented in two or more monographs. For adequate assessment by the membership,
it was concluded that the prototype should include at least five chapters which would relate directly to five of the monographs included in the prototype. As a supplemental aid in providing the practitioner with necessary information, a chapter discussing drug interactions in general was proposed. This chapter would not cover a specific class of drugs but rather would attempt to summarize the basic concepts necessary for a broader and deeper understanding of the overall problem area. Such a chapter has been included and is liberally illustrated. It is anticipated that if the Board of Trustees decides to proceed with the complete compilation, it will be essen-
tially identical to the prototype. Of course, one objective of preparing the prototype was to assess how adequately it fulfilled the needs of the practitioner. In all probability, before advancing to the complete compilation, the concept embodied in the prototype will be modified and refined, based on the suggestions of the members, within economic, staff and printer limitations. • Acknowledgments The limited time available for the preparation of the prototype made great demands on the time of Review and Practitioner Panel members. Their conscientiousness in adhering to a decidedly difficult schedule is evident in the on~time publication. Their cooperation, interest, concern and suggestions through the course of this project were greatly appreciated.
Women's Auxiliary
A Year's Experiences Enjoyable, rewarding, enlightening, even frustrating, but never dull are a few of the words that describe the experiences of this past year, a year in which I have met with and spoken with men and women interested in pharmacy, some more than others. This has been a year in which I've had my first experience with deadlines-for this column, for the directory, for the newsletters, for the program. Each month immediately after sending in the column, you begin to think about the subject of the next one. After writing it and seeing it in print, you sometimes wonder if the column is actually being read. Some of the things the postman brings ... the complimentary comments of friends are certainly appreciated but the letters which bring joy are the ones from the pharmacy student who has read about the loan fund; the pharmacist requesting an application for membership for his wife; the woman who wants to become a member; the requests for information on affiliation, on poison prevention, legislation, drug abuse and the Achievement Awards. All these letters have one thing in common-they learned about the Auxiliary from the column in the Journal. These letters indicate that the monthly column is doing what it was originally intended to do. Not just deeds ... the presidents of local auxiliaries with 202
Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION
whom I spoke at our state meeting impressed me with their sincere interest in working at the community level, not only with words but with their actual involvement with poison awareness, drug abuse, mass immunization programs, as well as raising monies for scholarships. Future leaders ... the student wives-eager, aware and fully cognizant of their responsibilities as the wives of future pharmacists will be a welcome addition to the local, state and national auxiliary. Local involvement ... the newsletters received periodical.ly from some of our local branches reveal an increased effort on the part of the membership to become involved. A salute to my co-workers ... all these things and more have made this year most rewarding-the cooperation and willingness of the members of the board to lend a helping hand, sometimes on very short notice; the untiring efforts of the local arrangements chairman and the members of her committees in planning a meeting that will have something for everyone. I salute these ladies who have been so gracious with their time and energy in the interest of the APhA Women's Auxiliary. Helen I. Lowe 3105 Silverleaf Dr. Austin, TX 78757
Drug Interactions Pilot Project*
Evaluations of Drug
Interactions
American Pharmaceutical Association
By L. Luan Corrigant
growing concern relative to the . problem of drug interactions developed within the profession in the late 1960's. This concern was vocalized by a number of professionals; within the APhA Academy of General Practice of Pharmacy, members urged the development by APhA of a compendium of drug interactions. During this period of developing interest and concern, a number of reviews and compilations were prepared and published by various individuals and organizations. It was generally felt, however, that these compilations did not really meet the requirements and desires of the practicing pharmacist. As elaborated by AGP members, the practitioner needed concise information relative to drug interactions and, at the same time, this information had to be comprehensive enough to allow the practitioner to arrive at intelligent judgments concerning various drug therapies.
A
Evolution of Pilot Project It was noted that the available compilations generally tended simply to abstract the literature without attempting to evaluate it, producing a situation in which one article might be published on a particular interaction,
0 This report will summarize the various activities of the APhA Drug Interactions Pilot Project and will elaborate on some of the decisions that went into the development and publication of the pilot version of "Evaluations of Drug Int eractions." The pilot project was directed by Edward G. F e.ldm_ann, APhA associate executive director for sctenttfic affairs, with Richard P. Penna, secretary of the Academy of General Practice of Pharmacy, as project advisor.
t Miss Corrigan is an administrative assistant in the. APhA Scientific Division. She was a project ass!stant in the pilot study and is the technical edttor of the prototype version of "Evaluations of Drug Interactions."
200
abstracted in another and then cited in another. Finally, all three might show up in another article as three separate pieces of evidence for the alleged interaction. It was recognized early in the Drug Interactions Pilot Project that a review process analogous to that employed by the American Dental Association's Council on Dental Therapeutics, the American Medical Association's Council on Drugs, the NF Admissions Committee and the USP Subcommittee on Scope has general acceptance by the professions. It was felt that a review process such as this could cut through the confusion of the drug interactions literature and aid in arriving at authoritative, consensus opinions. The resolution developed by the APhA Committee on Professional Affairs and passed by the APhA House of Delegates at the 1970 annual meeting called on APhA to "initiate a comprehensive study to make available to pharmacists information on drug interactions. Attention should be given to making this information available in a concise form which will include an explanation of the mechanism and clinical significance of specific drug interactions." To fulfill the directives within the resolution, it was necessary to study and evaluate the area of drug interactions for a better understanding of how best to deal with the problem. To achieve a clearer delineation of this problem area, a feasibility study was conducted by the APhA scientific division, under the direction of Edward G. Feldmann, associate executive director for scientific affairs. The report on the feasibility study made to the Board of Trustees in June 1970 indicated that the data collected for the study bore out previous indications that there was a need for a comprehensive and authoritative com-
Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION
pendium on drug interactions. Because of uncertainty relative to just how to approach the development of a new compendium and how to present the information for the most efficient use by the typical practitioner, the Board voted to proceed by way of the pilot project. A pilot project, climaxed by the publication of a prototype of the anticipated compendium, would fulfill several necessary functions. First, it would establish if the envisioned review process would indeed result in useful and applicable information for the practitioner. Second, it would provide an opportunity to work out various production and layout problems that would affect the projected compilation. Third, it would allow for a thorough review of an actual product by a representative sampling of the membership and by other interested parties. Although operating under a rigorous schedule, it was felt that the prototype publication could be available for limited distribution at the 1971 annual meeting in San Francisco. Having the prototype available for distribution at the annual meeting would in itself provide .much initial feedback concerning its suitability. As additional opportunities for feedback, Dr. Feldmann spoke before meetings of pharmacy practitioners in San Francisco. Because the publication of the prototype was undertaken literally on a crash basis, it was impossible to provide all those in attendance at the annual meeting with copies. However, it was essential that the opinions of the membership about the prototype be adequately assessed, since the compilation was to be prepared for their use. To determine the response of the membership, a random selection of several thousand members was made from the association's membership ros-
ter; the mailing of review copies to this sampling was begun shortly after the annual meeting. A questionnaire covering basic aspects of the prototype was included in the booklet to facilitate response by those who reviewed and evaluated the prototype. Development of Prototype The prototype, "Evaluations of Drug Interactions (EDI) ," is a seventy-page booklet that contains representative drug interactions and related topics prepared by the participants of the Drug Interactions Pilot Project. The prototype includes the one-page questionnaire and four distinct sections, each section printed on a different color of paper for rapid identification. The four sections are -front matter (which includes the preface and introduction), monographs, chapters and index. The index is a key feature of the publication, designed to provide rapid access to the desired information. From the very early stages of the project, a review process similar to those already enumerated was conceived to be an essential part of the compilation. Hence, it was deemed necessary to utilize two distinct, but complementary, panels-a Review Panel, which would be responsible for compiling, reviewing and evaluating the literature on a specific drug interaction; and a Practitioner Panel, which would be responsible for determining the usefulness of the compiled information to the practitioner as well as the actual means of presenting that information for his most efficient use. While there already existed a substantial number of articles in the literature about drug interactions, the Practitioner Panel had to determine how this information should be divided or cataloged for use by the practitioner. ft was obvious that a certain amount of information was essential; the question became where to draw the line. How much information did the practitioner need to reach an intelligent judgment? How could the compilation be both concise and comprehensive? The Practitioner Panel suggested that the monographs should contain enough information to provide the practitioner with a firm base on which to make his decisions. The actual hows and whys of drug interactions should be provided, though not necessarily in the monographs. Hence, the concept of each monograph containing essentially the same If additional elements developed. background information would be helpful and necessary to understand the interaction discussed in the mono-
graphs, it would be included in a chapter. Therefore, with the aid of the Practitioner Panel, the pilot project members developed the following basic format for the monographsTitle-if sufficient information is known about the mechanism of the interaction, the first drug given in the title is the drug that is acted upon in the interaction, and the second drug mentioned is the drug that produces the interaction.
information I. Summary-includes concerning the clinical significance of the interaction as well as indicating some course of action. II. Related Drugs-gives the names of related drugs or drugs that might be expected to act in a similar manner. III. Pharmacological Effect and Mechanism-discusses some of the background information needed to understand why the interaction occurs and what its effects might be. IV. Evaluation of Clinical Data-summarizes the most significant studies or the most pertinent studies pertaining to the interaction. V. Clinical Significance-gives the relative significance of the interaction in practice. VI. Recommend a ti o ns-i ncludes courses of action, such as changes or adjustments in dosage or dosage forms as well as indicating the need for certain laboratory tests or other methods of surveillance.
VII. References-provides substantiation for data leading to the evaluations presented in the monographs. Nonproprietary and trade names of drugs are provided at the end of each monograph, set off in a box for quick location. While defining the scope of the monographs proceeded rather smoothly, delineating the material to be contained in the chapters proved more complex. The style or format of ~he chapters could not be so easily designated. When moving from a specific drug-drug interaction to an explanation of the phenomenon, quite a few variables are introduced, such as the state of knowledge concerning the particular disease condition, the number of alternate therapies, and the inherent nature of a particular class of drugs. It should be realized that if and when a complete compendium is prepared, the material in the chapters will undoubtedly be refined and the chapters made more consistent; however, the nature of the material and the intent of the chapters to provide additional and supplemental information preclude a totally consistent format and length. For the purposes of the prototype, the selection of the drug-drug interactions to be included was based on an attempt to provide a representative sampling of interactions, rather than an attempt to take the ten most well-documented interactions or the ten most serious interactions. By tak-
Review Panel Members William H. Barr, PharmD, PhD, assistant professor of pharmaceutics, State University of New York at Buffalo Edward A. Hartshorn, PhD, director of pharmacy services, Evanston Hospital, Evanston, Illinois Daniel A. Hussar, PhD, associate professor of pharmacy, Philadelphia College of Science and Pharmacy Robert E. Pearson, MS, project coordinator, Michigan Regional Drug Information Network, University Hospital, Ann Arbor, Michigan Fred J. Salter, PharmD, acting assistant director, Clinical Pharmacy Services, Medical College of Virginia Hospitals, Richmond James A. Visconti, PhD, assistant professor of pharmacy, director of Drug Information Center, Ohio State University, Columbus
Practitioner Panel Members Ernest H. Luther, BS, hospital pharmacist, Doctors Hospital Pharmacy, Inc., Fairfax, Virginia William E. Merritt, BS, community pharmacist, Johnson's Pharmacy, Greenville, Delaware William H. Randall, BS, community pharmacist, LaFayette Drug Company, Lillington, North Carolina Byron C. Spoon Jr., BS, community pharmacist, The Peoples Drug Company, Dayton, Ohio
Vol. NSll, No. 4, April 1971
201
ing this approach, it was hoped that a better picture of the proposed compendium would be provided. The interactions, therefore, in the prototype range from those that are recognized and documented to be clinically significant to some that have been alleged to be serious but are actually without foundation in the literature or in practice. The selection of the topics to be developed in the chapters was not quite so easily made. It was acknowledged that in the final compilation not every monograph would have a chapter; indeed, one chapter often would encompass the interactions presented in two or more monographs. For adequate assessment by the membership,
it was concluded that the prototype should include at least five chapters which would relate directly to five of the monographs included in the prototype. As a supplemental aid in providing the practitioner with necessary information, a chapter discussing drug interactions in general was proposed. This chapter would not cover a specific class of drugs but rather would attempt to summarize the basic concepts necessary for a broader and deeper understanding of the overall problem area. Such a chapter has been included and is liberally illustrated. It is anticipated that if the Board of Trustees decides to proceed with the complete compilation, it will be essen-
tially identical to the prototype. Of course, one objective of preparing the prototype was to assess how adequately it fulfilled the needs of the practitioner. In all probability, before advancing to the complete compilation, the concept embodied in the prototype will be modified and refined, based on the suggestions of the members, within economic, staff and printer limitations. • Acknowledgments The limited time available for the preparation of the prototype made great demands on the time of Review and Practitioner Panel members. Their conscientiousness in adhering to a decidedly difficult schedule is evident in the on~time publication. Their cooperation, interest, concern and suggestions through the course of this project were greatly appreciated.
Women's Auxiliary
A Year's Experiences Enjoyable, rewarding, enlightening, even frustrating, but never dull are a few of the words that describe the experiences of this past year, a year in which I have met with and spoken with men and women interested in pharmacy, some more than others. This has been a year in which I've had my first experience with deadlines-for this column, for the directory, for the newsletters, for the program. Each month immediately after sending in the column, you begin to think about the subject of the next one. After writing it and seeing it in print, you sometimes wonder if the column is actually being read. Some of the things the postman brings ... the complimentary comments of friends are certainly appreciated but the letters which bring joy are the ones from the pharmacy student who has read about the loan fund; the pharmacist requesting an application for membership for his wife; the woman who wants to become a member; the requests for information on affiliation, on poison prevention, legislation, drug abuse and the Achievement Awards. All these letters have one thing in common-they learned about the Auxiliary from the column in the Journal. These letters indicate that the monthly column is doing what it was originally intended to do. Not just deeds ... the presidents of local auxiliaries with 202
Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION
whom I spoke at our state meeting impressed me with their sincere interest in working at the community level, not only with words but with their actual involvement with poison awareness, drug abuse, mass immunization programs, as well as raising monies for scholarships. Future leaders ... the student wives-eager, aware and fully cognizant of their responsibilities as the wives of future pharmacists will be a welcome addition to the local, state and national auxiliary. Local involvement ... the newsletters received periodical.ly from some of our local branches reveal an increased effort on the part of the membership to become involved. A salute to my co-workers ... all these things and more have made this year most rewarding-the cooperation and willingness of the members of the board to lend a helping hand, sometimes on very short notice; the untiring efforts of the local arrangements chairman and the members of her committees in planning a meeting that will have something for everyone. I salute these ladies who have been so gracious with their time and energy in the interest of the APhA Women's Auxiliary. Helen I. Lowe 3105 Silverleaf Dr. Austin, TX 78757