mal out
gallbladder resorting
to a minimum with¬ to the inefficient recommendation of subjecting all pa¬ tients to the expense, inconvenience,
and
morbidity of a double dose of panoic acid over a 40-hour period.
io¬
Charles E. Shopfner, MD Mobile, Ala
1. Berk RN, Loeb PM,
lecystography
with
210, 1974. 2.
Goldberger LE, et al: Oral choiopanoic acid. N Engl J Med 290:204\x=req-\
Goldberger LE, Berk RN, Lang JH, et al: Biopharinfluencing the intestinal absorption
maceutical factors
iopanoic acid. Invest Radiol 9:16-23, 1974. 3. Koehler PR, Kyaw MM: Effect of fractionated administration of Telepaque on gallbladder visualization. Radiology 108:517-519, 1973. 4. Whalen JP, Rizzuiti RJ, Evans JA: Time of optimal of
gallbladder opacification with Telepaque (iopanoic acid). Radiology 105:523-524, 1972.
Stamp for Charting
measurement, irregularity, dimpling,
Breast Lesions To the
The stamp and design are illustrated in the Figure. The nipple and areola are centrally placed. Concentric circles are made; each intervening space represents a finger's breadth or, if desired, a metric measurement. Straight lines, corresponding to the numbers on a clock, are made from the edge of the areola to the outer edge of the circle. With this as a chart, masses, thickening, and other findings are accurately recorded in exact position, ie, two fingers' breadth from the areola at the 9 o'clock position. Solid masses may be designated by a solid mark, cysts with a plain circle, and thickening with a cross-hatched symbol. The or other pertinent facts recorded in the margins. This stamped diagram allows pre¬ cision in record keeping by showing on a patient's chart the exact loca¬ tion, size, and type of all lesions. Sub¬ sequent changes are easily noted by providing a visual method for recall and comparison. The method is rapid and timesaving and is stamped on the office examination sheet. It elimi¬ nates the need for lengthy word de¬
retraction, is
Editor.\p=m-\There increasing public awareness of the importance of
breast examination. When the patient is examined by the physician, the findings are recorded and should become a permanent part of the patient's file. They are recorded by brief or lengthy word descriptions or by the use of printed forms, drawn diagrams, or rubber stamp. A stamp diagram was designed that permits specific, precise, and accurate location and description of all breast lesions.
are
scriptions, rough drawings, or printed
charts and is also valuable in the follow-up of multiple aspirated cysts. The stamp is inexpensive and is read¬ ily available for use by physicians (Printing Place of Kensington, Ken¬ sington, MD 20795). In addition, at the discretion of the examiner, the patient can be provided with copies of stamped imprints for recording find¬ ings on self-examination. Daniel J. Abramson, MD
Army Medical Center Washington, DC Walter Reed
Breast stamp and
diagram.
New Drugs for Hypertension: An FDA Reply To the Editor.\p=m-\In an editorial (229:689, 1974), Dr Edward D. Freis charged the Food and Drug Administration (FDA) with depriving American physicians and their patients of a number of useful antihypertensive drugs. Such "drug lag" editorials have appeared in various journals in the past, and we are not able to respond to all of them. This particular editorial, however, has generated numerous inquiries to the FDA, undoubtedly because of the importance of hypertension and the prominence of Dr Freis. I would therefore like to comment on some of the points he raises and correct several inaccuracies. A more complete discussion of
Downloaded From: http://jama.jamanetwork.com/ by a Oakland University User on 06/11/2015
the drug lag issue by the FDA can be found in our testimony before subcommittees of the senate committees on labor and public welfare and on the judiciary on Aug 16 and Sept 27, 1974. Dr Freis cited the absence from the United States of three antihypertensive drugs popular in the United
Kingdom: bethanidine, debrisoquin, propranolol (available here but not labeled for treatment of hyper¬ tension). He stated that applications for these drugs were submitted to and
the FDA many years ago and that debrisoquin was disapproved while the others "have not been acted on as yet." The basic problem was attrib¬ uted to "endless delay and procrasti¬ nation" resulting from the "individ¬ ual reviewing officer who is unable or unwilling to arrive at a fair judgment of the benefit-risk ratio of a new drug." Unfortunately, these allega¬ tions are incorrect and serve only to perpetuate misconceptions about FDA review procedures. New drug applications (NDAs) for debrisoquin and bethanidine were submitted to the FDA in 1964 and 1966, respectively. Both applications were disapproved because of the lack of controlled studies providing ade¬ quate evidence of safety and effec¬ tiveness, and neither NDA sponsor has ever submitted a subsequent ap¬ plication. Dr Freis' concerns thus re¬ late to his disagreement with judg¬ ments and regulatory decisions made a number of years ago, rather than to untimely review procedures or pro¬ crastination. Marketing rights to bethanidine have been transferred to a different manufacturer, who has ac¬ tively supported clinical studies; an NDA for bethanidine is now under review. Clinical studies of debrisoquin were discontinued several years ago, and we are not aware of plans to mar¬ ket the drug in the United States. Propranolol also has not been sub¬ ject to a prolonged review by the FDA. Ayerst Laboratories first sub¬ mitted an application for propranolol for the treatment of hypertension in late December 1974. Such a submis¬ sion had been requested by FDA for about two years prior to that time. A supplemental application was sub¬ mitted in April 1975. Those appli¬ cations are currently under review. Whether medical practice in the United States is seriously impaired by the nonavailability of bethanidine and debrisoquin is difficult to de¬ termine. Guanethidine, a drug long
available in this country, has a mech¬ anism of action and side effects gen¬ erally similar to those of bethanidine, although bethanidine may have cer¬ tain advantages, particularly in caus¬ ing less diarrhea. It is difficult to know whether debrisoquin has any notable advantages, because the drug is not under study here. Since debrisoquin is an inhibitor of intraneuronal monamine oxidase, how¬ ever, it is said to carry a potential risk of causing hypertensive reactions. Propranolol, on the other hand, rep¬ resents a new mode of action among antihypertensive drugs and has the potential for being an important ad¬ vance in therapy. It is, of course, al¬ ready available to physicians in the United States for other indications, and its use in hypertension would have been reviewed much earlier if an application had been submitted by its manufacturer. Dr Freis suggested that review com¬ mittees of outside consultants might be used to "circumvent" FDA review¬ ers who could not reach a decision to approve or disapprove a new drug expeditiously and that such committees could begin by considering "cardio¬ vascular drugs that have been under consideration without decision for three years or longer." In response to this suggestion, I would emphasize two points: (1) There are no drugs that have been under consideration without decision for three years or longer. (2) The FDA has for several years made extensive use of advisory committees of outside consultants. Dr Freis has personally served the FDA as a
consultant to
our
Cardio-Renal
Advisory Committee. In recent years,
FDA management has devoted con¬ siderable attention to drug review policies, internal procedures, and the effective use of outside advisors. The Bureau of Drugs now has 18 scientific advisory committees associated with the new drug review process. They provide independent advice on mat¬ ters within their area of expertise, in¬ cluding the safety and effectiveness of important new drugs. They are not needed, and will not be used, to "cir¬ cumvent" the FDA staff, as sug¬ gested by Dr Freis. No responsible in¬ stitution should use consultants in this manner. Instead, we encourage an open working relationship be¬ tween FDA staff and committee members and a full exchange of views. For the most part, FDA staff and advisory committees reach sim¬ ilar conclusions and we have no evi-
dence that these committees are, in more or less inclined to rec¬ ommend the marketing of new drugs than our own staff. The Agency has strived in recent years to manage its workload profes¬ sionally, to open its decision-making process to public scrutiny, to consult widely, and to be fully sensitive to health needs and benefit-risk issues. Decisions may still proceed more slowly than many of us would like, but this is because the issues are com¬ plex and the work difficult. I would urge physicians concerned about the unavailability of a par¬ ticular drug to be sure of their facts before assuming that the fault lies with the FDA. Drugs are approved on the basis of evidence supplied by the drug firms. We are mutually respon¬ sible for the drug supply in this
general,
country:
J. Richard Crout, MD, Director Bureau of
Food and
Drugs Drug Administration
IPPB To the Editor.\p=m-\I have read with extreme interest the commentary in The Journal (231:1141,1975) on "The Indiscriminate Use of IPPB." For years, as a surgeon, I have been discussing this exact problem with many of my colleagues and have met deaf ears. One means of therapy that I believe is quite effective for postoperative atelectasis is transtracheal instillation of saline to stimulate coughing in atelectasis. This can be
performed by inserting a large intra-
catheter into the trachea and instilling saline in this every three to four hours. This clears up any atelectasis almost 100% of the time within 24 hours. I would like to have further comments made in your LETTERS TO THE EDITOR section regarding Drs Barach and Segal's article, because I believe that millions of dollars are spent each year on this wasteful procedure. Yorke G. Jacobson, MD
Antioch, Calif
To the Editor. \p=m-\DrsBarach and Segal are to be commended for their recent excellent article (231:1141,1975) alerting physicians to the indiscriminate use of the intermittent positive pressure breathing (IPPB) machine for
pulmonary conditions, such as acute asthma, that could be relieved by simpler and less expensive methods. An
additional drawback to use of the IPPB machine, and one that warrants emphasis, is the fact that some pa-
Downloaded From: http://jama.jamanetwork.com/ by a Oakland University User on 06/11/2015
tients with recurrent asthma, who have been indoctrinated by its use during a hospital stay to relieve their asthma, have purchased this apparatus for use at home and have become so dependent upon it that it often is difficult to wean them away from what has now become their crutch. They use this apparatus instead of a bronchodilator tablet or a hand nebulizer to relieve the slightest breathing disturbance, regardless of whether it is associated with actual wheezing or, as I have seen in some patients, when the breathing condition is of the sighing dyspnea or hyperventilation type. The IPPB appa¬ ratus undoubtedly can be helpful in selected cases, but one cannot empha¬ size too strongly the necessity for curbing its unnecessary utilization and abuse. MD Louis Tuft, Philadelphia
To the Editor.\p=m-\The commentary, "The Indiscriminate Use of IPPB" (231:1141, 1975) implies that the staff of a respiratory therapy department may be incompetent. I am sorry that Drs Barach and Segal work in an institution where the respiratory therapy staff find hand bulb nebulizers, spontaneous coughing, and deep breathing as "inappropriate and old fashioned." This respiratory therapy staff is not representative of all in the United States. A staff of professional respiratory therapists owe it to their patients to utilize the most beneficial and least expensive methods for treatment of physiological disorders. This type of staff often approaches the physician with recommendations for discontinuance of the use of IPPB and
implementation of coughing and deep breathing techniques. This does not
rule out IPPB as an effective modalin the treatment of patients that cannot, for a variety of reasons, effectively cough and deep breathe. The use of IPPB may very well be effective if these circumstances are pres¬ ent. Very seldom are patients within this institution sent home to purchase or rent IPPB units, nor does this in¬ stitution employ a "puffing parlor" for outpatients. The commentary suggests that the surgical patient should be taught the use of simpler techniques. This I agree with if the patient can manipu¬ late these devices and can compre¬ hend instructions for coughing and deep breathing. The commentary goes on to suggest that "these inex-
ity
gallbladder resorting
to a minimum with¬ to the inefficient recommendation of subjecting all pa¬ tients to the expense, inconvenience,
and
morbidity of a double dose of panoic acid over a 40-hour period.
io¬
Charles E. Shopfner, MD Mobile, Ala
1. Berk RN, Loeb PM,
lecystography
with
210, 1974. 2.
Goldberger LE, et al: Oral choiopanoic acid. N Engl J Med 290:204\x=req-\
Goldberger LE, Berk RN, Lang JH, et al: Biopharinfluencing the intestinal absorption
maceutical factors
iopanoic acid. Invest Radiol 9:16-23, 1974. 3. Koehler PR, Kyaw MM: Effect of fractionated administration of Telepaque on gallbladder visualization. Radiology 108:517-519, 1973. 4. Whalen JP, Rizzuiti RJ, Evans JA: Time of optimal of
gallbladder opacification with Telepaque (iopanoic acid). Radiology 105:523-524, 1972.
Stamp for Charting
measurement, irregularity, dimpling,
Breast Lesions To the
The stamp and design are illustrated in the Figure. The nipple and areola are centrally placed. Concentric circles are made; each intervening space represents a finger's breadth or, if desired, a metric measurement. Straight lines, corresponding to the numbers on a clock, are made from the edge of the areola to the outer edge of the circle. With this as a chart, masses, thickening, and other findings are accurately recorded in exact position, ie, two fingers' breadth from the areola at the 9 o'clock position. Solid masses may be designated by a solid mark, cysts with a plain circle, and thickening with a cross-hatched symbol. The or other pertinent facts recorded in the margins. This stamped diagram allows pre¬ cision in record keeping by showing on a patient's chart the exact loca¬ tion, size, and type of all lesions. Sub¬ sequent changes are easily noted by providing a visual method for recall and comparison. The method is rapid and timesaving and is stamped on the office examination sheet. It elimi¬ nates the need for lengthy word de¬
retraction, is
Editor.\p=m-\There increasing public awareness of the importance of
breast examination. When the patient is examined by the physician, the findings are recorded and should become a permanent part of the patient's file. They are recorded by brief or lengthy word descriptions or by the use of printed forms, drawn diagrams, or rubber stamp. A stamp diagram was designed that permits specific, precise, and accurate location and description of all breast lesions.
are
scriptions, rough drawings, or printed
charts and is also valuable in the follow-up of multiple aspirated cysts. The stamp is inexpensive and is read¬ ily available for use by physicians (Printing Place of Kensington, Ken¬ sington, MD 20795). In addition, at the discretion of the examiner, the patient can be provided with copies of stamped imprints for recording find¬ ings on self-examination. Daniel J. Abramson, MD
Army Medical Center Washington, DC Walter Reed
Breast stamp and
diagram.
New Drugs for Hypertension: An FDA Reply To the Editor.\p=m-\In an editorial (229:689, 1974), Dr Edward D. Freis charged the Food and Drug Administration (FDA) with depriving American physicians and their patients of a number of useful antihypertensive drugs. Such "drug lag" editorials have appeared in various journals in the past, and we are not able to respond to all of them. This particular editorial, however, has generated numerous inquiries to the FDA, undoubtedly because of the importance of hypertension and the prominence of Dr Freis. I would therefore like to comment on some of the points he raises and correct several inaccuracies. A more complete discussion of
Downloaded From: http://jama.jamanetwork.com/ by a Oakland University User on 06/11/2015
the drug lag issue by the FDA can be found in our testimony before subcommittees of the senate committees on labor and public welfare and on the judiciary on Aug 16 and Sept 27, 1974. Dr Freis cited the absence from the United States of three antihypertensive drugs popular in the United
Kingdom: bethanidine, debrisoquin, propranolol (available here but not labeled for treatment of hyper¬ tension). He stated that applications for these drugs were submitted to and
the FDA many years ago and that debrisoquin was disapproved while the others "have not been acted on as yet." The basic problem was attrib¬ uted to "endless delay and procrasti¬ nation" resulting from the "individ¬ ual reviewing officer who is unable or unwilling to arrive at a fair judgment of the benefit-risk ratio of a new drug." Unfortunately, these allega¬ tions are incorrect and serve only to perpetuate misconceptions about FDA review procedures. New drug applications (NDAs) for debrisoquin and bethanidine were submitted to the FDA in 1964 and 1966, respectively. Both applications were disapproved because of the lack of controlled studies providing ade¬ quate evidence of safety and effec¬ tiveness, and neither NDA sponsor has ever submitted a subsequent ap¬ plication. Dr Freis' concerns thus re¬ late to his disagreement with judg¬ ments and regulatory decisions made a number of years ago, rather than to untimely review procedures or pro¬ crastination. Marketing rights to bethanidine have been transferred to a different manufacturer, who has ac¬ tively supported clinical studies; an NDA for bethanidine is now under review. Clinical studies of debrisoquin were discontinued several years ago, and we are not aware of plans to mar¬ ket the drug in the United States. Propranolol also has not been sub¬ ject to a prolonged review by the FDA. Ayerst Laboratories first sub¬ mitted an application for propranolol for the treatment of hypertension in late December 1974. Such a submis¬ sion had been requested by FDA for about two years prior to that time. A supplemental application was sub¬ mitted in April 1975. Those appli¬ cations are currently under review. Whether medical practice in the United States is seriously impaired by the nonavailability of bethanidine and debrisoquin is difficult to de¬ termine. Guanethidine, a drug long
available in this country, has a mech¬ anism of action and side effects gen¬ erally similar to those of bethanidine, although bethanidine may have cer¬ tain advantages, particularly in caus¬ ing less diarrhea. It is difficult to know whether debrisoquin has any notable advantages, because the drug is not under study here. Since debrisoquin is an inhibitor of intraneuronal monamine oxidase, how¬ ever, it is said to carry a potential risk of causing hypertensive reactions. Propranolol, on the other hand, rep¬ resents a new mode of action among antihypertensive drugs and has the potential for being an important ad¬ vance in therapy. It is, of course, al¬ ready available to physicians in the United States for other indications, and its use in hypertension would have been reviewed much earlier if an application had been submitted by its manufacturer. Dr Freis suggested that review com¬ mittees of outside consultants might be used to "circumvent" FDA review¬ ers who could not reach a decision to approve or disapprove a new drug expeditiously and that such committees could begin by considering "cardio¬ vascular drugs that have been under consideration without decision for three years or longer." In response to this suggestion, I would emphasize two points: (1) There are no drugs that have been under consideration without decision for three years or longer. (2) The FDA has for several years made extensive use of advisory committees of outside consultants. Dr Freis has personally served the FDA as a
consultant to
our
Cardio-Renal
Advisory Committee. In recent years,
FDA management has devoted con¬ siderable attention to drug review policies, internal procedures, and the effective use of outside advisors. The Bureau of Drugs now has 18 scientific advisory committees associated with the new drug review process. They provide independent advice on mat¬ ters within their area of expertise, in¬ cluding the safety and effectiveness of important new drugs. They are not needed, and will not be used, to "cir¬ cumvent" the FDA staff, as sug¬ gested by Dr Freis. No responsible in¬ stitution should use consultants in this manner. Instead, we encourage an open working relationship be¬ tween FDA staff and committee members and a full exchange of views. For the most part, FDA staff and advisory committees reach sim¬ ilar conclusions and we have no evi-
dence that these committees are, in more or less inclined to rec¬ ommend the marketing of new drugs than our own staff. The Agency has strived in recent years to manage its workload profes¬ sionally, to open its decision-making process to public scrutiny, to consult widely, and to be fully sensitive to health needs and benefit-risk issues. Decisions may still proceed more slowly than many of us would like, but this is because the issues are com¬ plex and the work difficult. I would urge physicians concerned about the unavailability of a par¬ ticular drug to be sure of their facts before assuming that the fault lies with the FDA. Drugs are approved on the basis of evidence supplied by the drug firms. We are mutually respon¬ sible for the drug supply in this
general,
country:
J. Richard Crout, MD, Director Bureau of
Food and
Drugs Drug Administration
IPPB To the Editor.\p=m-\I have read with extreme interest the commentary in The Journal (231:1141,1975) on "The Indiscriminate Use of IPPB." For years, as a surgeon, I have been discussing this exact problem with many of my colleagues and have met deaf ears. One means of therapy that I believe is quite effective for postoperative atelectasis is transtracheal instillation of saline to stimulate coughing in atelectasis. This can be
performed by inserting a large intra-
catheter into the trachea and instilling saline in this every three to four hours. This clears up any atelectasis almost 100% of the time within 24 hours. I would like to have further comments made in your LETTERS TO THE EDITOR section regarding Drs Barach and Segal's article, because I believe that millions of dollars are spent each year on this wasteful procedure. Yorke G. Jacobson, MD
Antioch, Calif
To the Editor. \p=m-\DrsBarach and Segal are to be commended for their recent excellent article (231:1141,1975) alerting physicians to the indiscriminate use of the intermittent positive pressure breathing (IPPB) machine for
pulmonary conditions, such as acute asthma, that could be relieved by simpler and less expensive methods. An
additional drawback to use of the IPPB machine, and one that warrants emphasis, is the fact that some pa-
Downloaded From: http://jama.jamanetwork.com/ by a Oakland University User on 06/11/2015
tients with recurrent asthma, who have been indoctrinated by its use during a hospital stay to relieve their asthma, have purchased this apparatus for use at home and have become so dependent upon it that it often is difficult to wean them away from what has now become their crutch. They use this apparatus instead of a bronchodilator tablet or a hand nebulizer to relieve the slightest breathing disturbance, regardless of whether it is associated with actual wheezing or, as I have seen in some patients, when the breathing condition is of the sighing dyspnea or hyperventilation type. The IPPB appa¬ ratus undoubtedly can be helpful in selected cases, but one cannot empha¬ size too strongly the necessity for curbing its unnecessary utilization and abuse. MD Louis Tuft, Philadelphia
To the Editor.\p=m-\The commentary, "The Indiscriminate Use of IPPB" (231:1141, 1975) implies that the staff of a respiratory therapy department may be incompetent. I am sorry that Drs Barach and Segal work in an institution where the respiratory therapy staff find hand bulb nebulizers, spontaneous coughing, and deep breathing as "inappropriate and old fashioned." This respiratory therapy staff is not representative of all in the United States. A staff of professional respiratory therapists owe it to their patients to utilize the most beneficial and least expensive methods for treatment of physiological disorders. This type of staff often approaches the physician with recommendations for discontinuance of the use of IPPB and
implementation of coughing and deep breathing techniques. This does not
rule out IPPB as an effective modalin the treatment of patients that cannot, for a variety of reasons, effectively cough and deep breathe. The use of IPPB may very well be effective if these circumstances are pres¬ ent. Very seldom are patients within this institution sent home to purchase or rent IPPB units, nor does this in¬ stitution employ a "puffing parlor" for outpatients. The commentary suggests that the surgical patient should be taught the use of simpler techniques. This I agree with if the patient can manipu¬ late these devices and can compre¬ hend instructions for coughing and deep breathing. The commentary goes on to suggest that "these inex-
ity
