3. Twenty-three percent of the patients in the control group showed marked or moderate improvement when no specific drug treatment was used. This represents the proportion of patients expected to improve with other standard forms of hospital treatment.

4. All three of the phenothiazines were equally successful and showed a strong overall effect against nearly all schizophrenic symptoms. The variety of symptoms affected by the drugs suggests that they have a basic antipsychotic action. They not only helped the hostile, overactive patient, but also greatly benefited the apathetic, withdrawn patient.

5. The drugs alleviated the classic schizophrenic symptoms of hallucinations, thinking or speech disorders, bizarre motor behavior, inappropriate emotion, and helped improve personal relations. They were less effective against feelings of guilt, delusions of grandure, and loss of memory. 6. Side effects generally were mild despite the higher dosages required for patients of this sort. The more common side reactions were limited to drowsiness, dizziness, and dry mouth.

The study has important implications for the treatment of mental illness, one of the nation's major health problems. About half the patients in U.S. hospitals are psychiatric cases, with half of these, schizophrenic. The authors conclude "The findings of this study lend strong support to the rising optimism about ⚫ the treatment of acute schizophrenic psychoses. The effects of phenothiazine therapy are not only quantitative they are also qualitative in that a wide range of schizophrenic symptoms and behavior are favorably altered."

The hospitals participating in the study were: Boston State Hospital, Boston, Mass.; District of Columbia General Hospital, Washington, D.C.; Kentucky State Hospital, Danville, Ky.; Malcolm Bliss Mental Health Center, St. Louis, Mo.; Mercy-Douglass Hospital, Philadelphia, Pa.; Payne-Whitney Clinic, New York City, N.Y.; Rochester State Hospital, Rochester, N.Y.; Springfield State Hospital, Sykesville, Md.; Institute of Living, Hartford, Conn. The data were analyzed by the Biometric Laboratory, George Washington University, Washington, D.C., and by the Psychopharmacology Service Center.

APhA is accepting its share of the responsibility to reduce the risk factor in the benefit-to-risk ratio. We have informed the Food and Drug Administration that the more than 100,000 active practitioners of pharmacy who dispense 800 million prescription orders annually represent an undeveloped source of information about adverse drug

reactions.

Our specialty affiliate, the American Society of Hospital Pharmacists, cooperated in the FDA pilot project (exhibits 3 and 4) on reporting adverse drug reactions observed in hospitalized patients. Since this project was first launched in 1955, the profession of pharmacy has studied its potential role in collecting and recording this valuable information.

EXHIBIT 3-EDITORIAL, BY DON E. FRANCKE, AMERICAN PHARMACEUTICAL

ASSOCIATION

[American Journal of Hospital Pharmacy, May 1959]

REPORTING ADVERSE DRUG REACTIONS IN HOSPITALS

A relatively new activity of Pharmacy and Therapeutics Committees, which assist in the formulation of broad professional policies relative to all aspects of drugs, is the study of adverse drug reactions in hospitals. This development was spearheaded during the presidential term of Dr. George Archambault when the Food and Drug Administration approached the ASHP to explore the feasi bility of establishing some type of cooperative approach to obtain vital information on untoward effects of drugs. In 1955 a pilot study was undertaken by the Food and Drug Administration and the American Association of Medical Record Librarians, in collaboration with the ASHP, the American Medical Association and the Pharmacy and Therapeutics Committees of five hospitals. This project has since been expanded to include additional hospitals. Summaries of several reports on adverse drug reactions have been issued. One summary reported 235

adverse reactions to drugs occurring in eleven hospitals during a period of approximately thirteen months. These results show the need for more hospitals to establish a procedure for studying adverse reactions to drugs. While the method of handling this problem must necessarily vary from hospital to hospital, the procedure recommended by the Pharmacy and Therapeutics Committee of one hospital may be of interest. The following is quoted from the minutes of a recent meeting of such a Committee:

"Adverse Drug Reactions.-At the March 1958 meeting of the Committee it was moved, seconded, and carried that a simple form for use in reporting adverse drug reactions is desirable and, further, that the Secretary of the Pharmacy and Therapeutics Committee be requested to prepare such a form and submit it to the Committee for approval, and that the form as approved by the Pharmacy and Therapeutics Committee be submitted at a later date to the Senior Medical Advisory Staff for consideration.

"The Secretary discussed briefly the pilot studies on adverse drug reactions being carried out by the Food and Drug Administration in several hospitals with the cooperation of various groups.

"VOTED TO RECOMMEND

"It was moved, seconded, and carried that the following policy for reporting adverse reactions to drugs be recommended to the Senior Medical Advisory Staff for approval:

"That a method of reporting adverse drug reactions to Chiefs of Departments and Sections of the medical staff and to the Pharmacy and Therapeutics Committee be adopted in the interest of better patient care and teaching.

"In the discussion of the motion. the following points were made.

"1. Need.-The increasing number of potent and potentially dangerous drugs makes it advisable, from a teaching as well as a patient care viewpoint, for the medical staff to be familiar with the overall incidence and extent of adverse reactions.

"2. Definition of Adverse Reaction.-The definition used by the Food and Drug Administration is as follows: 'An adverse drug reaction includes any pathological condition precipitated by a drug regardless of its nature or the circumstances of its occurrence; i.e., toxicity caused by overdosage (therapeutic, accidental, suicidal, homicidal), hypersensitivity; allergy; or injury from improper technique of administration, use of the wrong drug, error in compounding, labeling, or packaging, or from other error in the manufacture of the drug, or in its preparation for use in the hospital. Reactions caused by blood and plasma products and other biologics need not be reported unless a chemical agent other than the basic substance is responsible. For example, if sodium citrate in whole blood were to cause a reaction, the case should be reported, with this offending agent designated.'

"According to the above definition, a report would be made only when the patient (1) developed a pathological condition as a result of using the drug, (2) developed a hypersensitivity or allergy, or (3) suffered injury from the drug. It would exclude reporting instances in which the wrong medicine is administered or in which the drug was improperly labeled, if no harm resulted to the patient. These latter incidents would be reported to the hospital authorities by Nursing as at present.

"3. Form To Be Used.—It was recommended that a modification of the form developed by the Food and Drug Administration be used for reporting adverse drug reactions in this hospital. The form would be modified (1) so that the patient's name could be stamped in the upper right hand corner and (2) a small duplicate 3 x 5 card would be attached on which only the patient's name would appear, together with the words Report of Adverse Drug Reaction.'

4. Procedure.-When an adverse drug reaction occurs on the nursing unit, the nurse, or at her discretion, the ward clerk will stamp the patient's name (1) in the upper right-hand corner of the FDA form and add the name of the physician and place it in the physician's reference booklet, and (2) on the attached card which is to be sent by the nurse to the Pharmacy for filing and to serve as a check when the completed report is received. If the physician and not the nurse observes the drug reaction he will obtain the form from the nurse or ward clerk.

"The physician is to complete the FDA form and send it to the Secretary of the Pharmacy and Therapeutics Committee (Director of Pharmacy Service) who will transmit photocopies to the Chiefs of the appropriate Departments and Sections and to the Pharmacy and Therapeutics Committee.

"The Pharmacy and Therapeutics Committee will study and analyze the report and present a summary of findings and recommendations to the medical staff, which may be used for teaching purposes and to improve patient care.

"Hospital pharmacists are being continuously encouraged to expand their actitivies beyond the four walls of the Pharmacy. Establishment of a procedure for reporting adverse reactions to drugs represents another opportunity to promote better patient care though cooperative activity."

EXHIBIT 4-STATEMENT OF THE PHARMACY AND THERAPEUTICS COMMITTEE Approved by the Board of Trustees of the American Hospital Association and the Executive Committee of the American Society of Hospital Pharmacists, February 1959

[American Journal of Hospital Pharmacy, March 1959)

PREAMBLE

Hospitals organize and marshal the best professional skills and judgment available to provide care and treatment of patients. The treatment of these patients in many cases is dependent upon the effective use of drugs. The multiplicity of drugs available today makes it mandatory that an organized sound program of activity be developed within the hospital to insure that patients receive the best care and protection possible.

One of the most effective ways of providing this kind of care and protection is by organizing a Pharmacy and Therapeutics Committee. This committee is designed to make maximum use of available professional skills and judgment. The establishment of a Pharmacy and Therapeutics Committee is strongly recommended to all hospitals. It is a measure which supports and enhances the principle of self-government in the area of high drug standards and practices for the medical staff connected with a hospital. Ultimate benefits accrue to the patient in improved patient care and treatments established voluntarily by the medical staff.

THE PHARMACY AND THERAPEUTICS COMMITTER

The Pharmacy and Therapeutics Committee is an advisory group of the medical staff and serves as the organizational line of communication or liaison between the medical staff and the pharmacy department. This committee is composed primarily of physicians and the pharmacist and is selected under the guidance of the medical staff. It is also a policy-recommending body to the medical staff and to the administration of the hospital on all matters related to the use of drugs. (This committe does not have intrinsic authority or power of action unless specifically granted such authority.)

Purposes

The primary purposes of the Pharmacy and Therapeutics Committee are: A. Advisory. The committee recommends the adoption or assists in the formulation of broad professional policies regarding evaluation, selection, procurement, distribution, use, safe practices, and other matters pertinent to drugs in hospitals. B. Educational.-The committee recommends or assists in the formulation of programs designed to meet the needs of the professional staff (doctors, nurses, and the pharmacist) for complete current knowledge on matters related to drugs and drug practices.

Organization

While the composition of the Pharmacy and Therapeutics Committee may vary from hospital to hospital, the following is offered as a guide:

A. The Pharmacy and Therapeutics Committee of the medical staff should be composed of no less than three physicians and the pharmacist, appointed by a governing unit or elected official of the organized medical staff. The hospital administrator or his designated representative should be an ex officio member of the committee.

B. A chairman from the physician representatives should be appointed. The pharmacist is generally designated secretary.

C. The Pharmacy and Therapeutics Committee should meet regularly, no less frequently than twice per year, and should meet on call when necessary. 37-272-64-pt. 1-17

D. The committee should feel free to invite to its meetings persons within or without the hospital who can contribute from their specialized knowledge or experience.

E. An agenda is desirable and should be prepared and submitted to members of the committee in sufficient time before the meeting.

F. Minutes should be kept by the secretary and should be maintained in the permanent records of the hospital.

G. Recommendations of the Pharmacy and Therapeutics Committee shall be presented to the medical staff or its appropriate committee for adoption or recommendation.

Functions and scope

The basic organization of the hospital and medical staffs will determine the functions and scope of the Pharmacy and Therapeutics Committee. The following list, which is not necessarily comprehensive, is offered as a guide:

A. To serve in an advisory capacity to the medical staff and hospital administration in all matters pertaining to the use of drugs.

B. To serve in an advisory capacity to the medical staff and the pharmacist in the selection or choice of drugs which meet the most effective therapeuticquality standards.

C. To evaluate objectively clinical data regarding new drugs or agents proposed for use in the hospital.

D. To prevent unnecessary duplication of the same basic drug or its combinations.

E. To recommend additions and deletions from the list of drugs accepted for use in the hospital.

F. To develop a basic drug list or formulary of accepted drugs for use in the hospital and to provide for its constant revision.

G. To make recommendations concerning drugs to be stocked in hospital: patient units or services.

H. To establish or plan suitable educational programs for the professional staff on pertinent matters related to drugs and their use.

I. To recommend policies regarding the safe use of drugs in hospitals, including a study of such matters as investigational drugs, hazardous drugs, and others.

J. To study problems involved in proper distribution and labeling of medications for inpatients and outpatients.

K. To study problems related to the administration of medications.

L. To review reported adverse reactions to drugs administered.

M. To evaluate periodically medical records in terms of drug therapy. As an aside, the pharmacists practicing in hospitals are participating in the AMA program described by Dr. Hussey a few minutes ago. As a result of our experience we can see that medical and pharmacy practitioners will have to be motivated to take the necessary time to report adverse drug reactions. If a national reporting system does not result in timely feedback to the practitioners in the field they will become indifferent to the value and necessity of the program. Also, the public will have to be educated about the nature and cost of this program.

With electronic data processing, we now have the potential of recording the kind of information about the individual patient and his drug regimen that will permit researchers to unfold some of the mysteries surrounding side effects and the particular characteristics of the drug which trigger or produce them. We have no illusions about the magnitude of this task; it will take time, money, and scientific imagination and leadership. It would be a real tragedy-in our concern with the safety and efficacy of those new drugs which by Federal law must be dispensed on prescription order-if we overlooked the drugs which do not require a prescription order. There are times when patients innocently jeopardize their health or life by taking proprietary preparations that are incompatible with the prescription medication which has been ordered by their physician.

In testimony last August before the Senate's Subcommittee on Health, the American Pharmaceutical Association revealed the layman's problem of selecting drugs for self-medication which are both effective and safe for his particular use. APhA cited the role the pharmacist can play in helping to educate the lay person to recognize the approximate boundaries of his own therapeutic competence, and the dangers inherent in attempting to exceed them.

While we recognize that this subcommittee and these hearings are not directly concerned, we do believe that you will be interested in learning that APhA last September took the initiative by recommending that legislative consideration now be given to the reclassification of drugs in America. Today we have under Federal law only two classes of drugs-those which require a prescription order and those which do not.

The profession of pharmacy is now discussing the specifics of a recommendation to the Congress and Johnson administration which would result in four classes of drugs:

1. To be dispensed on prescription order and renewable at the prescriber's discretion only;

2. To be initially dispensed on prescription order only, but renewable at the pharmacist's discretion;

3. To be dispensed personally by the pharmacist at the request of the patient; and

4. To be directly available to the public without professional direction or control.

For the information of the subcommittee, we have attached our statement which was originally planned for presentation September 12, 1963, before the Senate Subcommittee on Reorganization and International Organizations. The statement was not presented, but has been filed with the Senate subcommittee with the request that it be included in the record. APhA believes that discussion of drug safety and the policies and procedures of the Food and Drug Administration would be incomplete without consideration of certain points which are outlined in detail in that statement.

In conclusion, it is the opinion of the American Pharmaceutical Association that public interest in drug safety is having a salutary effect on all governmental agencies, the health professions, and drug manufacturers to improve their efforts to protect the public health and the individual citizens who require drugs. But it is also our opinion that the general public and individual patients must be informed that a benefit-to-risk ratio will always exist, and that every effort is being made to reduce the risk and increase the benefit.

As Dr. Feldmann commented editorially over a year ago:

any drug-like everything else we use in everyday life of necessity has a degree of fundamental hazard connected with it. The sooner that this basic fact is brought home to all those using drugs, the sooner we will have a sophisticated public utilizing the benefits of drugs with a proper realization of the cautions which must be exercised and the potential dangers which cannot be completely divorced from any drug therapy (exhibit 5).

The Congress and all of us who are directly involved with drugs recognize that hundreds of thousands of our fellow men will be condemned to earlier deaths or longer periods of incapacity and suffering if new drugs are not available or presently available drugs are not utilized. We must all work together to combat hysteria about drug safety.