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Clinical TrialsDesign, Conduct and Analysis$

Curtis L. Meinert

Print publication date: 1986

Print ISBN-13: 9780195035681

Published to Oxford Scholarship Online: September 2009

DOI: 10.1093/acprof:oso/9780195035681.001.0001

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(p.309) B. Sketches of selected trials

(p.309) B. Sketches of selected trials

Source:
Clinical Trials
Publisher:
Oxford University Press

  • B.1 Introduction

  • B.2 Methods

  • B.3 Results

  • Table B-1 List of trials sketched

  • Table B-2 Abstract summaries of trials sketched

  • Table B-3 Publication list of sketched trials

  • Table B-4 Summary tabulations from sketches

  • Table B-5 Sample sketch for the UGDP

  • Table B-6 Data coordinating centers for multi-center trials referenced in this book

B.1 INTRODUCTION

Table B–1 provides a list of the trials sketched in this Appendix. They are all multicenter trials, except the Physicians’ Health Study (Sketch 1), and they all involve periods of follow-up of a year or longer. They represent seven different disease areas. The majority of the trials involve cardiovascular disease. The National Institutes of Health (NIH) serve as the sole source of support for 11 of the 14 trials, and they share funding responsibilities with a European foundation in the case of the International Reflux Study in Children. One of the other two trials was funded by the Veterans Administration and the other was funded by a pharmaceutical firm.

Eight of the trials involved tests of drugs, four involved surgical procedures, and one, the Hypertension Prevention Trial (HPT), involved testing diet modifications as preventive measures for hypertension. The remaining trial, the Multiple Risk Factor Intervention Trial (MRFIT), involved testing several different forms of intervention, all aimed at reducing known risk factors for heart disease.

The sketches are designed to:

  • Acquaint readers with the design and operating features of some typical long-term trials

  • Supplement information contained in the body of this book on some of the more frequently cited trials

  • Provide a data resource for tabulations presented in chapters throughout the book

B.2 METHODS

The initial draft of each sketch was prepared by the senior author using:

  • Published manuscripts produced from the trial (see Table B–3 for publication list)

  • Basic design documents, such as original funding applications or requests for proposals

  • Operational documents, such as manuals of operations, treatment protocols, data forms, etc.

  • Personal communications with study personnel

Each sketch consisted of:

  • An abstract summary of the trial

  • A list of study publications

  • Enumeration of the operating features of the trial

A copy of the draft sketch was sent to the chairman or vice-chairman of the study, director of the coordinating center or data coordinating center, or project officer for review. The date the review was completed (see item 33, Table B–4) was used as the cutoff date for information contained in the sketch and is considered the completion date for the sketch. Committee listing and membership information (items 27, 28, and 29, Table B–4) are as of this date for trials that had not yet entered the patient close-out stage. The committee structure is characterized as of the start of the close-out stage for trials that were already in this or in a later stage when the sketch was reviewed. Information on the steering committee and the committee responsible for treatment monitoring, as represented in items 28 and 29 of Table B–4, is based on data in the sketch (see Table B–5 for sample) and was collected on a supplementary form that was completed by the individual chosen to review the sketch.

B.3 RESULTS

Table B–2 contains the abstract summary of each trial sketched. Table B–3 lists official papers of the 14 study groups. Only papers appearing (p.310) in peer review journals or periodicals are listed. The list does not include:

  • Papers published after the date in item 33, Table B–4

  • Papers in preparation, submitted for publication but still under review, or accepted for publication but not yet published as of the date in item 33, Table B–4

  • Abstracts or editorials concerning the study

  • Papers published as part of a book, monograph, or the like, except where papers so published are part of a periodical indexed by the National Library of Medicine

  • Reports published by the federal government

  • Reports and documents placed on deposit at the National Technical Information Service or other similar repositories

The full list of publications is much more extensive than is shown in Table B–3 for some of the trials sketched, such as NCGS and CASS.

The author citations in Table B–3 are reproduced as supplied from the study, via the individual who reviewed the sketch, except for the exclusions listed above and minor editing. A comparison of citations in the table with those appearing in the body of the book will reveal differences. For example, named authors appear in the author field of citation 5.2 in Table B–3. The author designation in the body of the book for this citation is simply the National Cooperative Gallstone Study Group.

There are several reasons for the differences in the citations. First, it is not always clear how a paper should be listed from the arrangement of information in the masthead of the paper. Second, preference was given to corporate author designations when there was a choice between a conventional or corporate format in the body of the book. Use of corporate designations yielded shorter citations and made for a more logical grouping of related publications appearing in the combined bibliography (Appendix I) at the end of this book. Third, the listings in Table B–3 as supplied by the individuals selected to review the sketches were used to answer item 31.b in Table B–4. This was considered to provide the best basis for making the counts needed for that item.

Table B–4 contains summary tabulations derived from the sketches (See Table B–5 for sample sketch). The notes below relate to those tabulations. Table B–6 contains the name of the director of the data coordinating center or coordinating center and address of the center for all trials sketched, as well as the other multicenter trials referenced in this book. (p.311) (p.312)

(p.313)

Item number in Table B-4

Comment

1

• See Glossary for definition of type of trial.

2

• See Chapter 9 or Glossary for definition of fixed sample size design. All trials were of this type. None involved a sequential design.

3

• See Chapter 3 or Glossary for definitions of stages. The category Completed was checked if all funding for the trial had terminated by the date recorded in item 33.

5

• See Glossary for definitions.

6

• See Chapter 21.

7

• See Glossary for definitions of direct, indirect, and consortium awards.

8

• Start of funding taken as date of first award to any center in the trial. Awards issued simply for planning purposes were not counted in fixing the date. The ending date is the projected date for termination of all financial support for the trial. It is the termination date for completed trials.

9

• Number of clinics as of sketch completion for trials in the treatment and follow-up stage or earlier stage. Number of clinics entering the patient close-out stage for trials in that stage or beyond as of the sketch completion date given in item 33.

10

• See Glossary for definitions.

11. b

• Degree of coordinating center or data coordinating center director. Indicated as Bio (biostatistics), Epi (epidemiology), or Med (medicine).

11.c

• Answered No if the coordinating center or data coordinating center was financially and administratively independent of all other centers in the trial. Answered Yes if the center was funded through a clinical center in the trial or if it was under the administrative control of a clinic center director.

12, 13, 17

• See Glossary for definitions.

19.a

• See Chapter 14. Direct checked when potential study patients were identified and approached by study personnel, such as when patients are recruited from a primary care facility under the control of clinic investigators, or when patients are identified through special screening or direct mailings initiated by clinic personnel. Indirect checked if the initial contact is through some other agent or party outside the clinic, such as a referring physician, through review of records held by nonstudy physicians or at nonstudy hospitals, or via mass advertising compaigns initiated from the study and aimed at the general public.

19.b

• Month and year first patient was randomized.

19.c

• Month and year last patient was randomized. Projected date for trials still in the patient recruitment stage.

19.d

• Total number of patients enrolled (all treatment groups combined). Count at or before the date given in item 33.

20.a

• All 14 trials involved formal methods of randomization, as opposed to informal, nonrandom, or quasi-random methods, such as discussed in Chapter 8. All trials used patients as the randomization unit except one, the Macular Photocoagulation Study in which eyes served as the randomization unit.

20. b

• See Glossary for defninitions.

20.d

• The total number of allocation strata. Given by the product of the number of subgroups formed with each stratification variable. For example, a trial involving stratification by clinic (10 clinics), age (three levels), and sex would have 10 × 3 × 2 = 60 allocation strata.

20.e

• See Chapter 10 and Glossary for definitions. Characterized as uniform if the allocation scheme was designed to yield equal numbers of assignments to the study treatments within a strata. Classified as nonuniform (denoted as Nonuni in the table) if this condition does not apply.

20.f

• Answered Yes if the allocations are blocked (see Chapter 10) to force the treatment assignments to satisfy a specified allocation ratio at various points during the patient enrollment process.

20.g

• Locus of control for the randomization classified as Central if release of individual assignments was triggered by written or telephone contact of clinic staff with staff of the coordinating center or data coordinating center (or staff of some other control center), or release was controlled via an on-site computer under the control of the coordinating center or data coordinating center. Control considered Local if clinic staff could obtain an allocation without use of an on-site computer controlled by the coordinating center or data coordinating center or without any contact with a coordinating center or other control facility.

21

• See Chapter 12 and Glossary for definitions. Regular follow-up visits do not include visits done simply for treatment application or adjustment.

22.a

• Recorded as the average length of follow-up or as a range. Anticipated values for trials that had not yet entered the patient close-out stage. Ranges recorded for trials in the close-out stage or beyond based on actual times of enrollment of the first and last patients entered into the study.

22.b

• Indicated as NA (not applicable) for trials still in the patient close-out stage or an earlier stage. Indicated as None done if trial is completed and no post-trial follow-up was done. The average length of follow-up provided or anticipated if post-trial follow-up was done or is under way.

24

• See Chapters 8 and 15.

26.a

• Original recruitment goal: That set when the trial was planned. Value recorded is as stated in the original design documents of the trial (e.g., original grant application, RFP, or RFA), or as reported in a study publication.

26.b

• The category Sample size calculation was checked if the goal was based on a sample size calculation with a specified level of type I and II error protection. The category Pragmatic was checked if a recruitment goal was set, but was based on practical considerations rather than on a formal sample size calculation.

26.c

• The number of patients recruited (all treatments combined). Listed as NA (not applicable) if recruitment not yet completed as of date in item 33.

26.d

• Answer based on information in published reports of results from the listed trials (see Table B–3 for list). The category Not applicable checked for trials that have yet to publish any results. The category None required checked for trials that produced a significant effect before patient recruitment was completed. The category None stated checked if the treatment effect observed was not considered to be significant by the authors of the report and the report contains no discussion of the rationale for the achieved sample size, or of the power provided to detect a specified treatment difference with the observed sample size and control event rate. The category Sample size calculation checked if the original recruitment goal was achieved and if the goal was the result of a sample size calculation made during or prior to the close of the patient recruitment stage. The category Pragmatic checked if recruitment was completed and the report contains a statement indicating the achieved sample was the result of practical considerations (i.e., was not the result of a formal sample size calculation). A check in both categories Power calculation and Sample size calculation indicates the report satisfied the requirements for both categories.

27

• See Chapter 23 and Glossary for definitions.

28.a, ii

• Patient care responsibilities? Answered Yes if chairman was responsible for treatment or care of any patients in the trial.

28.a, iii

• Recorded as Self-appt (self-appointed) in investigator-initiated trials where the chairman was designated on the initial application. Recorded as E (elected) if chairman was chosen by the investigative group after the trial was funded, either by acclamation or through a formal election. Recorded as Appt (appointed) if chairman was selected by the sponsor or the advisory-review committee of the trial.

28.a, iv

• Recorded as W̅T̅ (without term) if the chairman, regardless of whether self-appointed, elected, or appointed, serves without term. Recorded as Term if chairman selected or appointed for a specified term less than the expected duration of the trial.

28.b, ii through iv

28.c, i

• See comments for 28.a, ii through iv.

• The study centers referred to in this item and in item 28.c, ii include clinical centers, as well as all resource centers. The number of members and their voting status is based on information supplied in study publications and as supplied from the study on a special form completed by the individual selected to review the sketch, as described in Section B.2.

28.d

• See Glossary for definitions of the positions listed. The positions denoted by items i through vi that were represented on the steering committee (SC) are marked Yes. No indicates that the position exists in the study, but that it is not represented on the SC. Positions that do not exist in the study are marked NA (not applicable). The positions represented by items vii and viii were marked Yes if individuals of the type indicated were on the SC, and were marked No if not.

28.e

• This item indicates the number of individuals elected to membership on the SC by some body of the study—generally the entire investigative body. The letter T following the number indicates election for a specified term. The letters WT indicate election without term.

29.a

• The committee scheduled to perform the treatment effects monitoring function for trials where monitoring is not yet under way. The actual committee performing that function for all other trials. See Glossary and Chapter 23.

29. b through f

• See comments for 28.a through e.

29.g

• The actual or planned number of meetings per year of the committee listed in item 29.a.

30

• See Chapter 23 for distinguishing features of communication models. Classifications made by author.

31.a

• Number from Table B–3.

31.b

• A paper was counted in the first category (corporate format) if the author field, as displayed in Table B–3, only contained the study name. It was counted in the second category (conventional format) if the author field only contained names of individual authors. It was counted in the third category (both formats) if the author field contained both the study name and the name of one or more authors.

32

• Item used to indicate the degree of involvement of the senior author of this book in the particular trials sketched.

33

• Taken as the date of review, as discussed in Section B.2.

Table B-1 List of trials sketched

Sketch number

Study name

Acronym

Disease

Sponsor

1

Physicians’ Health Study

PHS

Cancer, cardiovascular

NIH

2

University Group Diabetes Program

UGDP

Diabetes

NIH

3

VA Cooperative Studies Program Number 43

VA 43

Diabetes

VA

4

Macular Photocoagulation Study

MPS

Eye

NIH

5

National Cooperative Gallstone Study

NCGS

Gallbladder

NIH

6

Coronary Drug Project

CDP

Cardiovascular

NIH

7

Aspirin Myocardial Infarction Study

AMIS

Cardiovascular

NIH

8

Persantine Aspirin Reinfarction Study

PARIS

Cardiovascular

Industry

9

Hypertension Detection and Follow-Up Program

HDFP

Cardiovascular

NIH

10

Multiple Risk Factor Intervention Trial

MRFIT

Cardiovascular

NIH

11

Coronary Artery Surgery Study

CASS

Cardiovascular

NIH

12

Program on the Surgical Control of Hyperlipidemia

POSCH

Cardiovascular

NIH

13

Hypertension Prevention Trial

HPT

Cardiovascular

NIH

14

International Reflux Study in Children

IRSC

Kidney

NIH and foundation

(p.314) (p.315) (p.316) (p.317)

(p.318)

Table B-2 Abstract summaries of trials sketched

  1. 1. Physicians’ Health Study (PHS)

    The PHS is a randomized, double-masked, placebo-controlled clinical trial designed to test the value of regular use of aspirin on all cause and cardiovascular mortality after 4.5 years of follow-up, as well as beta-carotene on total cancer incidence in the last 2.5 years of the trial. Patients are randomly assigned to one of the four treatments listed below.

    Treatment

    Dosage

    • Aspirin + beta-carotene: ASA + β

    • Aspirin + beta-carotene placebo: B. Sketches of selected trials

    • Aspirin placebo + beta-carotene: B. Sketches of selected trials

    • Aspirin and beta-carotene placebos: B. Sketches of selected trials

    • One (325 mg) aspirin tablet every other day. One (30 mg) beta-carotene capsule on alternate days.

    • One aspirin tablet every other day. One beta-carotene placebo capsule on alternate days.

    • One aspirin placebo tablet every other day. One beta-carotene capsule on alternate days.

    • One aspirin placebo tablet every other day. One beta-carotene placebo capsule on alternate days.

    Over 21,500 male physicians, 40 to 84 years of age at entry, are to be enrolled. Physicians volunteering to participate will receive their assigned medication via mail and will be asked to complete a short questionnaire first at 6-month and later at 1-year intervals after enrollment. The questionnaires will be collected by mail and will be used to assemble information on treatment adherence, treatment side effects, and morbidity. Participants are not required to make any clinic visits.

  2. 2. University Group Diabetes Program (UGDP)

    The UGDP was a randomized, controlled, multicenter clinical trial designed to evaluate the effectiveness of long-term hypoglycemic drug therapy in preventing or delaying the vascular complications of diabetes. Only newly diagnosed, noninsulin dependent, adult-onset diabetics were eligible for enrollment. The study started patient enrollment in early 1961. All patient follow-up terminated in 1975. A total of 1,027 patients were enrolled and randomly assigned to one of the treatments listed below.

    Treatment

    Dosage

    • Insulin variable: IVAR

    • Insulin standard: ISTD

    • Tolbutamide: TOLB

    • Phenformin: PHEN

    • Lactose placebo: PLBO

    • As much insulin (U-80 Lente Iletin or other insulins) per day as required to maintain “normal” blood glucose levels. Administered via subcutaneous injections.

    • 10, 12, 14, or 16 units of insulin (U-80 Lente lletin) per day, depending on patient body surface. Administered via subcutaneous injections.

    • 3 tablets per day, each containing 0.5 gms of tolbutamide.

    • 1 capsule per day during first week of treatment, thereafter 2 capsules per day; 50 mg of phenformin per capsule.

    • Number of tablets or capsules similar to those used for tolbutamide or phenformin treatments.

    The tolbutamide and phenformin treatments were terminated in 1969 and 1971, respectively, because of lack of efficacy. The two insulin treatments were continued to the end of planned patient follow-up (1975), but were not judged to be any more effective than placebo medications in prolonging life or in delaying the onset and development of vascular complications.

  3. 3. VA Cooperative Studies Program Number 43 (VA 43)

    The study is a long-term, randomized, double-masked, placebo-controlled clinical trial of aspirin and dipyridamole in diabetics with advanced vascular disease. The test treatment is a combination of aspirin and dipyridamole (one 325 mg tablet of aspirin and one 75 mg tablet of dipyridamole, three times per day). Patients assigned to placebo treatment received a prescription for a tablet schedule identical to that of the test-treated group. Patients in the trial had to have gangrene of the feet at enrollment or had to have had an amputation on one or both of their feet for gangrene in the last 12 months prior to enrollment. The study enrolled 231 patients. Recruitment was completed in May 1980. The study investigators plan to announce the results of the trial sometime in 1984.

  4. 4. Macular Photocoagulation Study (MPS)

    The MPS is a multicenter study designed to assess the value of photocoagulation in eyes with choroidal neovascularization. The study consists of two sets of trials. The first was started in 1979 and focuses on the assessment of argon laser photocoagulation in eyes with leaking choroidal neovascular membranes that are between 200 and 2,500 microns from the center of the foveal avascular zone (FAZ). The second set of trials, started in 1982, involves use of krypton laser photocoagulation. This mode of treatment is restricted to eyes that were judged ineligible for argon laser photocoagulation because the choroidal neovascular membranes to be treated fell within 200 microns of the FAZ. Both studies involve three different types of eye diseases, as outlined below.

    Type of eye disease

    Eligibility criteria

    • Senile macular degeneration (SMD)

    • Presumed ocular histoplasmosis (HISTO)

    • Idiopathic neovascular membrane (INVM)

    • Neovascularization; visible drusen bodies as large or larger than those defined by standard MPS fundus photographs; age ≥ 50 at entry.

    • Neovascularization; at least one atrophic scar (histo spot) in either eye; age ≥ 18 at entry.

    • Neovascularization; no evidence of SMD or any other cause for neovascularization; no drusen bodies greater than those defined by standard MPS fundus photographs; no histo spots in either eye.

    Eligible eyes in both sets of trials are randomly assigned to receive photocoagulation or no treatment. All patients are followed for changes in vision. The only results available from the trial through the date listed in item 33, Table B–4, relate to argon-treated SMD patients. Patient recruitment for that trial was terminated because of the apparent superiority of argon treatment. Of the SMD untreated eyes, 60% had reduced visual capacity by the eighteenth month of follow-up, compared with only 25% of the argon-treated SMD eyes.

  5. 5. National Cooperative Gallstone Study (NCGS)

    The NCGS was a double-masked, randomized, controlled, trial designed to assess the efficacy and safety of chenodiol (chenodeoxycholic acid) for dissolution of radiolucent gallstones. The treatments are outlined below.

    Treatment

    Dosage

    • High dose chenodiol: H

    • Low dose chenodiol: L

    • Placebo: P

    • 6 capsules per day, each containing 125 mg of chenodiol.

    • 6 capsules per day, each containing 62.5 mg of chenodiol.

    • 6 capsules per day, each containing 3 mg of sodium cholate.

    Nine hundred sixteen patients (not counting the 128 patients enrolled in a preliminary biopsy study) were enrolled, treated, and followed by the ten clinical centers participating in the trial. The percentages of patients with complete gallstone dissolution, after two years of treatment, as determined by radiographic metrology, were 13.5 for H, 5.2 for L, and 0.8 for P. Partial (over 50% dissolution) or complete dissolution occurred in 40.8% of H-treated patients, 23.6% of the L-treated patients, and 11.0% of the P-treated patients. Clinically significant hepatotoxicity requiring termination of the assigned treatment occurred in 3% of the H-treated patients and in 0.4% of the L-treated and P-treated patients.

  6. 6. Coronary Drug Project (CDP)

    The CDP was a double-masked, randomized, controlled clinical trial designed to evaluate the efficacy of several different lipid-influencing drugs in prolonging the lives of men (aged 30 through 64 at entry) with a prior history of myocardial infarction. The treatments investigated are listed below.

    Treatment

    Dosage per day *

    • Low dose estrogen: ESG1

    • High dose estrogen: ESG2

    • Clofibrate: CPIB

    • Dextrothyroxine: DT4

    • Nicotinic acid: NICA

    • Placebo: PLBO

    • 2.5 mg of mixed conjugated equine estrogen (Premarin®)

    • 5.0 mg of mixed conjugated equine estrogen (Premarin®)

    • 1.8g of ethyl alpha parachlorophenoxy-isobutyrate (Atromid-S®)

    • 6.0 mg of dextrothyroxine (Choloxin®)

    • 3.0 mg of nicotinic acid

    • 3.8g of lactose (placebo)

    (*) Patients were required to take 9 capsules per day (3 capsules 3 times a day) to receive the specified dosage. They were started on 3 capsules per day. They were stepped to 6 capsules per day 1 month later and then to 9 capsules per day 1 month thereafter. They were then maintained on 9 capsules per day, except where contraindicated.

    The study involved 55 clinics, a coordinating center, project office, central laboratory, ECG reading center, and drug procurement and distribution center. A total of 8,341 patients were enrolled. All patients were followed for a minimum of 5 years.

    The two estrogen and dextrothyroxine treatments were discontinued during the course of the trial because of lack of efficacy. In addition, the clofibrate and nicotinic acid treatments, while continued to the end of the trial, did not show any evidence of efficacy. The 5-year mortality rates were 20.0, 21.2, and 20.9 per 100 population for CPIB, NICA, and PLBO, respectively.

  7. 7. Aspirin Myocardial Infarction Study (AMIS)

    AMIS was designed to test the efficacy of aspirin in prolonging life in patients with a prior history of myocardial infarction. A total of 4,524 patients were enrolled and followed through the efforts of 30 clinical centers, a coordinating center, project office, central laboratory, ECG reading center, and drug procurement and distribution center. Patients assigned to aspirin treatment (ASA) received 1.0g of aspirin per day (two capsules per day, each containing 0.5g of aspirin). Patients assigned to the placebo treatment (PLBO) received a capsule schedule similar to that for aspirin-treated patients. Patients were followed for a minimum of 3 years.

    The study failed to show any benefit for ASA treatment. In fact, the 3-year mortality rate for the ASA treatment group was higher than that for the PLBO treatment group (9.6 versus 8.8 per 100 population).

  8. 8. Persantine Aspirin Reinfarction Study (PARIS)

    PARIS was an industry-sponsored randomized, controlled, clinical trial designed to test the efficacy of Persantine® (dipyridamole) and aspirin in prolonging lives of patients with an ECG-documented history of myocardial infarction (MI). The trial involved 2,026 patients. Clinics from both the United States and the United Kingdom participated. Patients were treated and followed for a minimum of 3 years. The treatments were as outlined below.

    Treatment

    Dosage

    • Persantine® + Aspirin; PR + ASA

    • Persantine® placebo + Aspirin: B. Sketches of selected trials

    • Persantine® placebo + Aspirin placebo: B. Sketches of selected trials

    • 2 tablets, 3 times per day. 1 containing 75 mg of Persantine® and the other containing 324 mg of aspirin.

    • 2 tablets, 3 times per day. 1 containing 324 mg of aspirin and the other containing placebo medication.

    • 2 tablets, 3 times per day. Both containing placebo medication (starch, calcium phosphate, and microcrystalline cellulose).

    There was no significant difference among the treatment groups in mortality. The percentages dead at the end of the study were 10.7, 10.5, and 12.8 for the B. Sketches of selected trials treatment groups, respectively. However, subgroup analyses of the data suggested the combination of Persantine® and aspirin may be beneficial in prolonging life, if used within a few months following an MI. This finding led to initiation of PARIS, Part II (not sketched).

  9. 9. Hypertension Detection and Follow-Up Program (HDFP)

    The HDFP was a randomized, controlled, clinical trial of stepped care versus referred care for patients with hypertension. The study involved 14 clinics, a coordinating center, project office, central laboratory, ECG reading center, and a drug procurement and distribution center. A total of 10,940 men and women with a qualifying diastolic blood pressure (DBP) of 90 mmHg or higher were enrolled. Patients assigned to stepped care were treated at the study clinics by clinic personnel using a treatment protocol calling for stepped increases in the dosage of a prescribed medication or in the number of antihypertensive agents used in order to achieve desired BP reductions. Patients assigned to the referred care group were referred to their usual source of medical care for treatment.

    Five-year mortality (all cause) was 17% lower for the stepped care group than for the referred care group (6.4 per 100 population for stepped care versus 7.7 per 100 population for referred care). The investigators concluded that the findings “indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large number of people with high BP in the population, including those with ‘mild’ hypertension.”

  10. 10. Multiple Risk Factor Intervention Trial (MRFIT)

    MRFIT was a randomized, controlled, clinical trial designed to assess the value of a multifactor intervention program aimed at reducing known risk factors for coronary heart disease (CHD). The three risk factors were elevated serum cholesterol, high blood pressure, and cigarette smoking. Only men aged 35 through 57 at entry, with no overt evidence of CHD, were eligible for enrollment. The 12,866 men enrolled were randomly assigned to either special intervention (SI) or usual care (UC). Those assigned to SI were placed on specific treatments for the risk factors present. A dietary approach was used for cholesterol reduction, antihypertensive drugs (plus weight reduction where appropriate) were used for blood pressure reduction, and a behavioral approach was used to achieve cessation or reduction of cigarette smoking. Participants assigned to UC were not given any care via study clinics for elevated blood pressure or advice on how to reduce cholesterol or cigarette consumption. However, hypertensives diagnosed via the study were referred to their usual source of care for treatment.

    The trial completed participant recruitment in early 1976. Participants assigned to SI continued to be exposed to the required interventions until termination of follow-up in early 1982. The first report of findings appeared in late 1982. The report showed the interventions practiced on the SI-treated group to be effective in lowering blood pressure, cholesterol, and cigarette consumption. However, these reductions had virtually no effect on mortality. There was a slight but nonsignificant reduction in deaths from coronary heart disease (17.9 versus 19.3 per 100 population for the SI-treated versus the UC-treated groups). However, all cause mortality was slightly higher in the SI-treated group than in the UC-treated group (4.1 versus 4.0 per 100 population). Subgroup analyses presented in the 1982 publication raise the possibility that SI-treated men with hypertension and resting ECG abnormalities at entry may have fared worse than the corresponding UC-treated group of men.

  11. 11. Coronary Artery Surgery Study (CASS)

    CASS is a multicenter study consisting of two components: A trial designed to assess the efficacy of coronary artery surgery in patients with proven coronary artery disease and a registry of consecutive patients undergoing coronary arteriography. The trial component involved 780 patients assigned to coronary bypass surgery or conventional medical therapy. The registry is made up of 24,959 patients, including randomized patients. Patients in both components are followed for mortality, as well as for various nonfatal cardiovascular events. The study involves 15 clinical centers, a coordinating center, project office, and ECG reading center. Results comparing surgical and medical treatment in the randomized portion of the study had not been published, as of the completion date for this sketch.

  12. 12. Program on the Surgical Control of Hyperlipidemia (POSCH)

    POSCH is a randomized clinical trial designed to determine whether reducing cholesterol levels via partial ileal bypass, in patients with high cholesterol levels and a prior history of myocardial infarction (MI), is useful in prolonging life and mitigating atherosclerosis. Patients in the trial are randomly assigned to bypass surgery or regular medical care. Patient recruitment is scheduled to continue through May 1983 with the goal being to enroll 800+ patients. Follow-up is expected to continue for a minimum of 5 years after completion of recruitment. There are no publications containing treatment results, as of the date in item 33, Table B–4.

  13. 13. Hypertension Prevention Trial (HPT)

    The HPT is a randomized, controlled, multicenter trial designed to assess the efficacy of different forms of dietary intervention in preventing the development of hypertension. Current funding is for the first stage of a possible two-stage effort. The first stage is designed to develop and test methods and procedures needed for the second stage and will involve 800 participants randomly assigned to the treatment groups indicated below. The second stage, if warranted by results from the first stage, may involve as many as 6,000 participants and is expected to start in 1985 or 1986.

    Treatment

    Dietary goal

    High weight strata

    • Sodium restriction: Na

    • Sodium restriction and potassium supplementation: NaK

    • Sodium restriction plus caloric restriction for weight reduction: NaCal

    • Caloric restriction for weight reduction: Cal

    • Control: Ct

    • Reduce sodium intake to ≤ 70 mEq per day.

    • Reduce sodium intake to ≤ 70 mEq per day and increase potassium intake to ≥ 100 mEq per day.

    • Reduce sodium intake to ≤ 70 mEq per day and restrict calorie intake to bring body weight within normal limits.

    • Reduce calorie intake to bring body weight within normal limits.

    • None.

    Normal weight strata

    • Sodium restriction: Na

    • Sodium restriction and potassium supplementation: NaK

    • Control: Ct

    • Reduce sodium intake to ≤ 70 mEq per day.

    • Reduce sodium intake to ≤ 70 mEq per day and increase potassium intake to ≥ 100 mEq per day.

    • None.

    Only nonhypertensive individuals with diastolic blood pressures ≥ 78 mm Hg but < 90 mm Hg are eligible for enrollment in the first stage. Individuals who fall in the high weight strata, as determined by Quetelet’s Index, are assigned to any one of the five treatments listed above. Individuals who are not considered to be overweight by this index are assigned either to the control treatment or to one of the two dietary treatments not involving caloric restriction.

    The dietary goals stated above are pursued via a series of group counseling sessions in which individuals are shown how to shop, cook, and eat to achieve the desired goals. The counseling process will be maintained over the course of the trial. All participants will be followed for a period of 2 to 3 years for blood pressure changes.

  14. 14. International Reflux Study in Children (IRSC)

    The IRSC is a randomized, controlled, clinical trial of surgical versus conventional medical treatment of vesicoureteral reflux (VUR) in children under the age of ten at entry. The study involves a multinational set of clinics directed by a steering committee with representatives from Europe and the United States. Data collection in the United States is supervised by a data center based in New York. Data collection in Europe is supervised by a data center based in Essen. The German data center will serve as the analysis center for the combined United States-European data set.

    Grade III (European clinics only) and IV reflux patients are being enrolled and followed for evidence of renal scarring and measurement of renal growth. The trial has been under way for 3 years and is scheduled to continue for several more years. No results have been published as of the date in item 33, Table B–4.

(p.319) (p.320) (p.321) (p.322) (p.323) (p.324) (p.325)

(p.326)

Table B-3 Publication list of sketched trials

  1. 1. Physicians’ Health Study (PHS)

    None

  2. 2. University Group Diabetes Program (UGDP)

    1. 2.1 University Group Diabetes Program: A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. I: Design, methods and baseline characteristics. Diabetes 19(suppl 2): 747–783, 1970.

    2. 2.2 University Group Diabetes Program: A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II: Mortality results. Diabetes 19(suppl 2): 785–830, 1970.

    3. 2.3 University Group Diabetes Program: Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. III: Clinical implications of UGDP results. JAMA 218:1400–1410, 1971.

    4. 2.4 University Group Diabetes Program: Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. IV: A preliminary report on phenformin results. JAMA 217:777–784, 1971.

    5. 2.5 Prout TE, Knatterud GL, Meinert CL, Klimt CR: The University Group Diabetes Program: The UGDP Controversy: Clinical trials versus clinical impressions. Diabetes 21:1035–1040, 1972.

    6. 2.6 University Group Diabetes Program: A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. V: Evaluation of phenformin therapy. Diabetes 24(suppl 1):65–184, 1975.

    7. 2.7 University Group Diabetes Program: A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VI: Supplementary report on nonfatal events in patients treated with tolbutamide. Diabetes 25:1129–1153, 1976.

    8. 2.8 University Group Diabetes Program: Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII: Mortality and selected nonfatal events with insulin treatment. JAMA 240:37–42, 1978.

    9. 2.9 Prout T, Knatterud G, Meinert C: The University Group Diabetes Program: Diabetes drugs: Clinical trial (letter). Science 204:362–363, 1979.

    10. 2.10 University Group Diabetes Program: Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VIII: Evaluation of insulin therapy: Final report. Diabetes 31(suppl5):1–78, 1982.

  3. 3. VA Cooperative Studies Program Number 43 (VA 43)

    None

  4. 4. Macular Photocoagulation Study (MPS)

    1. 4.1 Macular Photocoagulation Study Group: Argon laser photocoagulation for senile macular degeneration. Arch Ophthalmol 100:912–918, 1982.

  5. 5. National Cooperative Gallstone Study (NCGS)

    1. 5.1 Croke G: Recruitment for the National Cooperative Gallstone Study. Clin Pharmacol and Ther 25:691–694, 1979.

    2. 5.2 Lachin JM, Marks JW, Schoenfield LJ; the NCGS Protocol Committee (Malcolm P. Tyor, Chairman, Peter H. Bennett, Scott M. Grundy, William G. M. Hardison, Lawrence W. Shaw, Johnson L. Thistle, Z. R. Vlahcevic) and the National Cooperative Gallstone Study Group: Design & methodological considerations in the National Cooperative Gallstone Study: A multi-center clinical trial. Controlled Clin Trials 2:177–229, 1981.

    3. 5.3 Lasser EC, Amberg JR, Baily NA, Varady P, Lachin J, Okun R, Schoenfield L: Validation of a computer-assisted method for estimating the number and volume of gallstones visualized by cholecystography. Invest Radiol 16:342–347, 1981.

    4. 5.4 Schoenfield LJ, Lachin JM, the Steering Committee (Baum RA, Habig RL, Hanson RF, Hersh T, Hightower NC, Jr., Hofmann AF, Lasser EC, Marks JW, Mekhjian H, Okun R, Schaefer RA, Shaw L, Soloway RD, Thistle JL, Thomas FB, Tyor MP), and the National Cooperative Gallstone Study Group: Chenodial (chenodeoxycholic acid) for dissolution of gallstones: The National Cooperative Gallstone Study. A controlled trial of efficacy and safety. Ann Intern Med 95:257–282, 1981.

    5. 5.5 Albers JJ, Grundy SM, Cleary PA, Small DM, Lachin JM, Schoenfield LJ, and the National Cooperative Gallstone Study Group: National Cooperative Gallstone Study: The effect of chenodeoxycholic acid on lipoproteins and apolipoproteins. Gastroenterology 82:638–646, 1982.

    6. 5.6 Fisher RL, Anderson DW, Boyer JL, Ishak K, Klatskin G, Lachin JM, Phillips MJ, and the Steering Committee for the National Cooperative Gallstone Study Group: A prospective morphologic evaluation of hepatic toxicity of chenodeoxycholic acid in patients with cholelithiasis: The National Cooperative Gallstone Study (NCGS). Hepatology 2:187–201, 1982.

    7. 5.7 Hofmann AF, Grundy SM, Lachin JM, Lan SP, Baum RA, Hanson RF, Hersh T, Hightower NC, Jr., Marks JW, Mekhjian H, Schaefer RA, Soloway RD, Thistle JL, Thomas FB, Tyor MP, and the National Cooperative Gallstone Study Group: Pretreatment biliary lipid composition in white patients with radiolucent gallstones in the National Cooperative Gallstone Study (NCGS). Gastroenterology 83:738–752, 1982.

    8. 5.8 Habig RL, Thomas P, Lippel K, Anderson D, Lachin J: Central laboratory quality control in the National Cooperative Gallstone Study. Controlled Clin Trials 4:101–123, 1983.

    9. 5.9 Lachin JM, Schoenfield LJ, and the National Cooperative Gallstone Study Group: Effects of dose relative to body weight in the National Cooperative Gallstone Study: A fixed-dose trial. Controlled Clin Trials 4:125–131, 1983.

    10. 5.10 Phillips MJ, Fisher RL, Anderson DW, Lan SP, Lachin JM, Boyer JL and the Steering Committee for the National Cooperative Gallstone Study Group. Ultrastructural evidence of intrahepatic cholestasis before and after chenodeoxycholic acid (CDCA) therapy in patients with cholelithiasis: The National Cooperative Gallstone Study (NCGS). Hepatology 3:209–220, 1983.

    11. 5.11 Schoenfield LJ, Grundy SM, Hofmann AF, Lachin JM, Thistle JL, Tyor MP, for the National Cooperative Gallstone Study: The National Cooperative Gallstone Study viewed by its investigators. Gastroenterology 84:644–648, 1983.

  6. 6. Coronary Drug Project (CDP)

    1. 6.1 Coronary Drug Project Research Group: The Coronary Drug Project: Initial findings leading to modifications of its research protocol. JAMA 214:1303–1313, 1970.

    2. 6.2 Coronary Drug Project Research Group: The Coronary Drug Project: Findings leading to further modifications of its protocol with respect to dextrothyroxine. JAMA 220:996–1008, 1972.

    3. 6.3 Coronary Drug Project Research Group: The prognostic importance of the electrocardiogram after myocardial infarction: Experience in the Coronary Drug Project. Ann Intern Med 77:677–689, 1972.

    4. 6.4 Coronary Drug Project Research Group: The Coronary Drug Project: Design, methods and baseline results. Circulation 47(suppl I): I–1—I–50 (plus appendixes), 1973.

    5. 6.5 Coronary Drug Project Research Group: The Coronary Drug Project: Findings leading to discontinuation of the 2.5-mg/day estrogen group. JAMA 226:652–657, 1973.

    6. 6.6 Coronary Drug Project Research Group: Prognostic importance of premature beats following myocardial infarction: Experience in the Coronary Drug Project. JAMA 223:1116–1124, 1973.

    7. 6.7 Coronary Drug Project Research Group: Factors influencing long-term prognosis after recovery from myocardial infarction: Three-year findings of the Coronary Drug Project. J Chronic Dis 27:267–285, 1974.

    8. 6.8 Coronary Drug Project Research Group: Left ventricular hypertrophy patterns and prognosis: Experience post-infarction in the Coronary Drug Project. Circulation 49:862–869, 1974.

    9. 6.9 Coronary Drug Project Research Group: The prognostic importance of premature ventricular complexes in the late post-infarction period: Experience in the Coronary Drug Project. Acta Cardiol (suppl 18):33–53, 1974.

    10. 6.10 Coronary Drug Project Research Group: The Coronary Drug Project. Clofibrate and niacin in coronary heart disease. JAMA 231:360–381, 1975.

    11. 6.11 Coronary Drug Project Research Group: Reply to letter from D. J. Gans. JAMA 234:22–23, 1975.

    12. 6.12 Coronary Drug Project Research Group: Aspirin in coronary heart disease. J Chronic Dis 29:625–642, 1976.

    13. 6.13 Coronary Drug Project Research Group: Serum uric acid: Its association with other risk factors and with mortality in coronary heart disease. J Chronic Dis 29:557–569, 1976.

    14. 6.14 Coronary Drug Project Research Group: The prognostic importance of plasma glucose levels and of the use of oral hypoglycemic drugs after myocardial infarction in men. Diabetes 26:453–465, 1977.

    15. 6.15 Coronary Drug Project Research Group: Gallbladder disease as a side-effect of drugs influencing Iipid metabolism: Experience in the Coronary Drug Project. N Engl J Med 296:1185–1190, 1977.

    16. 6.16 Coronary Drug Project Research Group: The Coronary Drug Project: Implications for clinical care. Primary Care 4:247–253, 1977.

    17. 6.17 Coronary Drug Project Research Group: The Coronary Drug Project Aspirin Study: Implications for clinical care. Primary Care 5:91–95, 1978.

    18. 6.18 Coronary Drug Project Research Group: The natural history of myocardial infarction in the Coronary Drug Project: Long-term prognostic importance of serum Iipid level. Am J Cardiol 42:489–498, 1978.

    19. 6.19 Coronary Drug Project Research Group: Clofibrate and gallbladder disease (letter). N Engl J Med 298:461, 1978.

    20. 6.20 Coronary Drug Project Research Group: Estrogens and cancer (letter). JAMA 239:2758–2759, 1978.

    21. 6.21 Coronary Drug Project Research Group: Reply to editorial by L. Carlson (letter). Atherosclerosis 30:239–241, 1978.

    22. 6.22 Coronary Drug Project Research Group: Reply to letter from C. A. Caceres and K. Enslein. JAMA 240:1483–1484, 1978.

    23. 6.23 Coronary Drug Project Research Group: Cigarette smoking as a risk factor in men with a prior history of myocardial infarction. J Chronic Dis 32:415–425, 1979.

    24. 6.24 Coronary Drug Project Research Group: Influence of adherence to treatment and response of cholesterol on mortality in the Coronary Drug Project. N Engl J Med 303:1038–1041, 1980.

    25. 6.25 Coronary Drug Project Research Group: Treatable risk factors—hypercholesterolemia, smoking, and hypertension—after myocardial infarction: Implications of the Coronary Drug Project data for clinical management. Primary Care 7:175–179, 1980.

    26. 6.26 Coronary Drug Project Research Group: Practical aspects of decision making in clinical trials: The Coronary Drug Project as a case study. Controlled Clin Trials 1:363–376, 1981.

    27. 6.27 Coronary Drug Project Research Group: Implications of findings in the Coronary Drug Project for secondary prevention trials in coronary heart disease. Circulation 63:1342–1350, 1981.

    28. 6.28 Coronary Drug Project Research Group: The natural history of coronary heart disease: Prognostic factors after recovery from myocardial infarction in 2789 men. The 5-year findings of the Coronary Drug Project. Circulation 66: 401–414, 1982.

    29. 6.29 Coronary Drug Project Research Group: High-density lipoprotein cholesterol and prognosis after myocardial infarction. Circulation 66:1176–1178, 1982.

  7. 7. Aspirin Myocardial Infarction Study (AMIS)

    1. 7.1 Aspirin Myocardial Infarction Study Research Group: A randomized, controlled trial of aspirin in persons recovered from myocardial infarction. JAMA 243:661–669, 1980.

    2. 7.2 Howard J, Whittemore AS, Hoover JJ, Panos M, and the Aspirin Myocardial Infarction Study Research Group: Commentary: How blind was the patient blind in AMIS? Clin Pharmacol Ther 32:543–553, 1982.

    3. 7.3 Wasserman AG, Bren GB, Ross AM, Richardson DW, Hutchinson RG, Rios JC: Prognostic implications of diagnostic Q waves after myocardial infarction. Circulation 65:1451–1455, 1982.

  8. 8. Persantine Aspirin Reinfarction Study (PARIS)

    1. 8.1 Persantine Aspirin Reinfarction Study Research Group: Persantine Aspirin Reinfarction Study: Design, methods, and baseline results. Circulation 62(suppl II):II-1—II–42, 1980.

    2. 8.2 Persantine Aspirin Reinfarction Study Research Group: Persantine and aspirin in coronary heart disease. Circulation 62:449–461, 1980.

  9. 9. Hypertension Detection and Follow-Up Program (HDFP)

    1. 9.1 Labarthe DR, Hawkins CM, Remington RD: Evaluation of performance of selected devices for measuring blood pressure. Am J Cardiol 32:546–553, 1973.

    2. 9.2 Remington RD: The Hypertension Detection and Follow-Up Program. Institut National de la Santé et de la Recherche Medicale (INSERM) 21:185–194, 1973.

    3. 9.3 Hypertension Detection and Follow-Up Program Cooperative Group (Borhani NO, Kass EH, Langford HG, Payne GH, Remington RD, Stamler J): The Hypertension Detection and Follow-Up Program. Prev Med 5:207–215, 1976.

    4. 9.4 Hypertension Detection and Follow-Up Program Cooperative Group: The Hypertension Detection and Follow-Up Program: A progress report. Circ Res 40(suppl I):I–106—I–109, 1977.

    5. 9.5 Hypertension Detection and Follow-Up Program Cooperative Group (Castle CH, Daugherty S, Detels R, Hawkins CM, Krishan I, Oberman A, Wassertheil-Smoller S): Blood pressure studies in 14 communities: A two-stage screen for hypertension. JAMA 237:2385–2391, 1977.

    6. 9.6 Hypertension Detection and Follow-Up Program Cooperative Group (Heymsfield S, Kraus J, Lee ES, McDill M, Stamler R, Watson R): Race, education and prevalence of hypertension. Am J Epidemiol 106:351–361, 1977.

    7. 9.7 Hypertension Detection and Follow-Up Program Cooperative Group (Apostolides A, Schnaper H, Stamler R, Taylor J, Tyler M, Wassertheil-Smoller S): Patient participation in a hypertension control program. JAMA 239:1507–1514, 1978.

    8. 9.8 Hypertension Detection and Follow-Up Program Cooperative Group (Apostolides A, Blaufox MD, Borhani NO, Cutter G, Daughtery S, Lewin AJ, Polk BF): Mild hypertensives in the Hypertension Detection and Follow-Up Program. Ann NY Acad Sci 304:254–266, 1978.

    9. 9.9 Hypertension Detection and Follow-Up Program Cooperative Group (Cutter G, Hebel JR, Labarthe D, Oberman A, Prineas R, Varady P): Variability of blood pressure and the results of screening in the Hypertension Detection and Follow-Up Program. J Chronic Dis 31:651–667, 1978.

    10. 9.10 Hypertension Detection and Follow-Up Program Cooperative Group (Blaufox MD, Curb D, Kralios A, Polk BF, Tyler M): Therapeutic control of blood pressure in the Hypertension Detection and Follow-Up Program. Prev Med 8:2–13, 1979.

    11. 9.11 Hypertension Detection and Follow-Up Program Cooperative Group: Five-year findings of the Hypertension Detection and Follow-Up Program: I. Reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA 242:2562–2571, 1979.

    12. 9.12 Hypertension Detection and Follow-Up Program Cooperative Group: Five-year findings of the Hypertension Detection and Follow-Up Program: II. Mortality by race-sex, and age. JAMA 242:2572–2577, 1979.

    13. 9.13 Wassertheil-Smoller S, Apostolides A, Miller M, Oberman A, Thorn T (on behalf of the Hypertension Detection and Follow-Up Program): Recent status of detection, treatment, and control of hypertension in the community. J Community Health 5:82–93, 1979.

    14. 9.14 Cowan L, Detels R, Farber M, Lee ES, McCray G, O’Flynn S, Parnell MJ (on behalf of the Hypertension Detection and Follow-Up Program): Residential mobility and long-term treatment of hypertension. J Community Health 5:159–166, 1980.

    15. 9.15 Cutter G, Heyden S, Kasteler J, Kraus JF, Lee ES, Shipley T, Stromer M (on behalf of the Hypertension Detection and Follow-Up Program): Mortality surveillance in collaborative trials. Am J Public Health 70:394–400, 1980.

    16. 9.16 Apostolides A, Cutter G, Daugherty SA, Detels R, Kraus J, Wassertheil-Smoller S, Ware J: Three-year incidence of hypertension in thirteen U.S. communities. Prev Med 11:487–499, 1982.

    17. 9.17 Curb JD, Hardy RJ, Labarthe DR, Borhani NO, Taylor JO: Reserpine and breast cancer in the Hypertension Detection and Follow-Up Program. Hypertension 4:307–311, 1982.

    18. 9.18 Hypertension Detection and Follow-Up Program Cooperative Group: Five-year findings of the Hypertension Detection and Follow-Up Program: III. Reduction in stroke incidence among persons with high blood pressure. JAMA 247:633–638, 1982.

    19. 9.19 Hypertension Detection and Follow-Up Program Cooperative Group: The effect of treatment on mortality in “mild” hypertension—Results of the Hypertension Detection and Follow-Up Program. N Engl J Med 307:976–980, 1982.

    20. 9.20 Kraus JF, Conley A, Hardy R, Sexton M, Sweezey Z: Relationship of demographic characteristics of interviewers to blood pressure measurements. J Community Health 8:3–12, 1982.

    21. 9.21 Shulman N, Cutter G, Daugherty R, Sexton M, Pauk G, Taylor MJ, Tyler M: Correlates of attendance and compliance in the Hypertension Detection and Follow-Up Program. Controlled Clin Trials 3:13–27, 1982.

    22. 9.22 Smith EO, Curb JD, Hardy RJ, Hawkins CM, Tyroler HA: Clinic attendance in the Hypertension Detection and Follow-UP Program: Hypertension 4:710–715, 1982.

    23. 9.23 Hardy RJ, Hawkins CM: The impact of selected indices of antihypertensive treatment on all-cause mortality. Am J Epidemiol 117:566–574, 1983.

    24. 9.24 Hypertension Detection and Follow-Up Program Cooperative Group (SA Daugherty, G Entwisle, JD Curb, BF Polk, JO Taylor, editors): Hypertension Detection and Follow-Up Program: Baseline characteristics of the enumerated, screened, and hypertensive participants. Hypertension 5(suppl 1V):IV-1—IV-205, 1983.

  10. 10. Multiple Risk Factor Intervention Trial (MRFIT)

    1. 10.1 Multiple Risk Factor Intervention Trial Group: Statistical design considerations in the NHLBI Multiple Risk Factor Intervention Trial (MRFIT). J Chronic Dis 30:261–275, 1977.

    2. 10.2 Zukel WJ, Paul O, Schnaper HW: The Multiple Risk Factor Intervention Trial (MRFIT): I. Historical perspective. Prev Med 10:387–401, 1981.

    3. 10.3 Sherwin R, Kaelber CT, Kezdi P, Kjelsberg MO, Thomas HE, Jr.: The Multiple Risk Factor Intervention Trial (MRFIT): II. The development of the protocol. Prev Med 10:402–425, 1981.

    4. 10.4 Benfari RC: The Multiple Risk Factor Intervention Trial (MRFIT): III. The model for intervention. Prev Med 10:426–442, 1981.

    5. 10.5 Caggiula AW, Christakis G, Farrand M, Hulley SB, Johnson R, Lasser NL, Stamler J, Widdowson G: The Multiple Risk Factor Intervention Trial (MRFIT): IV. Intervention on blood lipids. Prev Med 10:443–475, 1981.

    6. 10.6 Hughes GH, Hymowitz N, Ockene JK, Simon N, Vogt TM: The Multiple Risk Factor Intervention Trial (MRFIT): V. Intervention on smoking. Prev Med 10:476–500, 1981.

    7. 10.7 Cohen JD, Grimm RH, Jr., Smith WM: Multiple Risk Factor Intervention Trial (MRFIT): VI. Intervention on blood pressure. Prev Med 10:501–518, 1981.

    8. 10.8 Neaton JD, Broste S, Cohen L. Fishman EL, Kjelsberg MO, Schoenberger J: The Multiple Risk Factor Intervention Trial (MRFIT): VII. A comparison of risk factor changes between the two study groups. Prev Med 10:519–543, 1981.

    9. 10.9 Benfari RC, Sherwin R: The Multiple Risk Factor Intervention Trial after 4 years: A summing-up. Prev Med 10:544–546, 1981.

    10. 10.10 Multiple Risk Factor Intervention Trial Research Group: Multiple Risk Factor Intervention Trial: Risk factor changes and mortality results. JAMA 248:1465–1477, 1982.

  11. 11. Coronary Artery Surgery Study (CASS)

    1. 11.1 Kronmal RA, Davis K, Fisher LD, Jones RA, Gillespie MJ: Data management for a large collaborative clinical trial (CASS: Coronary Artery Surgery Study). Comput Biomed Res 11:553–566, 1978.

    2. 11.2 Davis K, Kennedy JW, Kemp HG, Jr., Judkins MP, Gosselin AJ, Killip T: Complications of coronary arteriography from the Collaborative Study of Coronary Artery Surgery (CASS). Circulation 59:1105–1112, 1979.

    3. 11.3 Weiner DA, Ryan TJ, McCabe CH, Kennedy JW, Schloss M, Tristani F, Chaitman BR, Fisher LD: Exercise stress testing: Correlations among history of angina, ST-segment response and prevalence of coronary artery disease in the Coronary Artery Surgery Study (CASS). N Engl J Med 301:230–235, 1979.

    4. 11.4 Chaitman BR, Rogers WJ, Davis K, Tyras DH, Berger R, Bourassa MG, Fisher L, Hertzberg VS, Judkins MP, Mock MB, Killip T: Operative risk factors in patients with left main coronary artery disease. N Engl J Med 303:953–957, 1980.

    5. 11.5 Kennedy JW, Kaiser GC, Fisher LD, Maynard C, Fritz JK, Myers W, Mudd JG, Ryan TJ, Coggin J: Multivariate discriminant analysis of the clinical and angiographic predictors of operative mortality from the Collaborative Study in Coronary Artery Surgery (CASS). J Thorac Cardiovasc Surg 80:876–887, 1980.

    6. 11.6 Vlietstra RE, Frye RL, Kronmal RA, Sim DA, Tristani FE, Killip T III, and participants in the Coronary Artery Surgery Study: Risk factors and angiographic coronary artery disease: A report from the Coronary Artery Surgery Study (CASS). Circulation 62:254–261, 1980.

    7. 11.7 Chaitman BR, Bourassa MG, Davis K, Rogers WJ, Tyras DH, Berger R, Kennedy JW, Fisher LD, Judkins MP, Mock MB, Killip T: Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). Circulation 64:360–367, 1981.

    8. 11.8 Chaitman BR, Fisher L, Bourassa MG, Davis K, Rogers WJ, Maynard C, Tyras DH, Berger RL, Judkins MP, Ringqvist I, Mock MB, Killip T: Effect of coronary bypass surgery on survival patterns in subsets of patients with left main coronary artery disease. Report of the Collaborative Study in Coronary Artery Surgery (CASS). Am J Cardiol 48:765–777, 1981.

    9. 11.9 Fisher LD, Kennedy JW, Chaitman BR, Ryan TJ, McCabe C, Weiner D, Tristani F, Schloss M, Warner HR: Diagnostic quantification of CASS (Coronary Artery Surgery Study) clinical and exercise test results in determining presence and extent of coronary artery disease. Circulation 63:987–1000, 1981.

    10. 11.10 Berger RL, Davis KB, Kaiser GC, Foster ED, Hammond GL, Tong TGL, Kennedy JW, Scheffield T, Ringqvist 1, Wiens RD, Chaitman BR, Mock M: Preservation of the myocardium during coronary artery bypass grafting. Circulation 64(suppl II):II-61–11–66, 1981.

    11. 11.11 Kennedy JW, Kaiser GC, Fisher LD, Fritz JB, Myers W, Mudd JG, Ryan TJ: Clinical and angiographic predictors of operative mortality from the Collaborative Study in Coronary Artery Surgery (CASS). Circulation 63:793–802, 1981.

    12. 11.12 Principal Investigators of CASS and their associates, T Killip (editor), LD Fisher, MB Mock (associate editors): The National Heart, Lung, and Blood Institute Coronary Artery Surgery Study (CASS). Circulation 63(suppl I):I–1—I–81, 1981.

    13. 11.13 Alderman EL, Fisher L, Maynard C, Mock MB, Ringqvist I, Bourassa MG, Kaiser GC, Gillespie MJ: Determinants of coronary surgery in a consecutive patient series from geographically dispersed medical centers: The Coronary Artery Surgery Study. Circulation 66(suppl I): I–6—I–15, 1982.

    14. 11.14 Faxon DP, Ryan TJ, Davis KB, McCabe CH, Myers W, Lesperance J, Shaw R, Tong TGL: Prognostic significance of angiographically documented left ventricular aneurysm from the Coronary Artery Surgery Study (CASS). Am J Cardiol 50:157–164, 1982.

    15. 11.15 Fisher LD, Judkins MP, Lesperance J, Cameron A, Swaye P, Ryan T, Maynard C, Bourassa M, Kennedy JW, Gosselin A, Kemp H, Faxon D, Wexler L, Davis KB: Reproducibility of coronary arteriographic reading in the Coronary Artery Surgery Study (CASS). Cathet Cardiovasc Diagn 8:565–575, 1982.

    16. 11.16 Fisher LD, Kennedy JW, Davis KB, Maynard C, Fritz JK, Kaiser G, Myers WO: The association of sex, physical size, and operative mortality after coronary artery bypass in the Coronary Artery Surgery Study (CASS). J Thorac Cardiovasc Surg 84:334–341, 1982.

    17. 11.17 Kemp H, Davis K, Judkins MP, Gosselin A, Kennedy JW, Cameron A, Swaye PS, Maynard C, Fisher LD: lntrareader variability in the interpretation of coronary arteriograms from the Coronary Artery Surgery Study (CASS). Ischemic heart disease: Second USA-USSR Symposium, Seattle, Washington, March 20, 1981. Kardiologiia 22:37–42, 1982.*

    18. 11.18 Kennedy JW, Killip T, Fisher LD, Alderman EL, Gillespie MJ, Mock MB: The clinical spectrum of coronary artery disease and its surgical and medical management, 1974–1979: The Coronary Artery Surgery Study. Circulation 66(suppl III):III–16—III–23, 1982.

    19. 11.19 Killip T: Indications for coronary arteriography. Ischemic heart disease: Second USA-USSR Symposium, Seattle, Washington, March 20, 1981. Kardiologiia 22:33–37, 1982.*

    20. 11.20 Lundberg ED, McBride R, Rawson TE, Mauritsen R, Ormond TH, Fisher LD, Kronmal RA, Gillespie MJ: C2: A data base management system developed for the Coronary Artery Surgery Study (CASS) and other clinical studies. J Med Systems 6:501–518, 1982.

    21. 11.21 Mock MB, Ringqvist I, Fisher LD, Davis KB, Chaitman BO, Kouchoukos NT, Kaiser GC, Alderman E, Ryan TJ, Russell RO Jr, Mullin S, Fray D, Killip T III, Participants in the Coronary Artery Surgery Study: Survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry. Circulation 66:562–568, 1982.

    22. 11.22 Rogers WJ, Chaitman BR, Fisher LD, Bourassa MG, Davis K, Maynard CL, Tyras DH, Berger RL, Judkins MP, Ringqvist I, Mock MB, Killip T: Comparison of the cumulative survival of medically and surgically treated patients with left main coronary artery disease: The CASS experience. Ischemic heart disease: Second USA-USSR Symposium, Seattle, Washington, March 20, 1981. Kardiologiia 22:53–57, 1982.*

    23. 11.23 Ryan TJ, Fisher LD, Weiner DA, McCabe CH, Chaitman B, Kennedy JW, Ferguson J, Tristani F: Experience with electrocardiographic exercise testing in the Coronary Artery Surgery Study (CASS). Ischemic heart disease, Second USA-USSR Symposium, Seattle, Washington, March 20, 1981. Kardiologiia 22:22–26, 1982.*

    24. 11.24 Vlietstra RE, Kronmal RA, Seth A, Frye RL: Correlation of risk factors for coronary artery disease with coronary angiographic findings. Ischemic heart disease: Second USA-USSR Symposium, Seattle, Washington, March 20, 1981. Kardiologiia 22:67–72, 1982.*

    25. 11.25 Vlietstra RE, Kronmal RA, Frye RL, Seth AK, Tristani FE, Killip T III: Factors affecting the extent and severity of coronary artery disease in patients enrolled in the Coronary Artery Surgery Study. Arteriosclerosis 2:208–215, 1982.

    26. 11.26 Weiner DA, McCabe CH, Ryan TJ, Chaitman BR, Sheffield LT, Ferguson J, Fisher LD: Assessment of the negative exercise test in 4373 patients from the Coronary Artery Surgery Study (CASS). J Cardiac Rehab 2:562–568, 1982.

    27. 11.27 Wexler LF, Lesperance J, Ryan TJ, Bourassa MG, Fisher LD, Maynard C, Kemp HG, Cameron A, Gosselin AJ, Judkins MP: Interobserver variability in interpreting contrast left ventriculograms (CASS). Cathet Cardiovasc Diagn 8:341–355, 1982.

    28. 11.28 Zimmern SH, Rogers WJ, Bream PR, Chaitman BR, Bourassa MG, Davis KA, Tyras DH, Berger R, Fisher L, Judkins MP, Mock MB, Killip TA: Total occlusion of the left main coronary artery: The Coronary Artery Surgery Study (CASS) experience. Am J Cardiol 49:2003–2010, 1982.

    29. 11.29 Chaitman BR, Alderman FL, Sheffield LT, Tong T, Fisher LD, Mock MB, Wiens RD, Kaiser GC, Roitman D, Berger R, Gersh B, Schaff H, Bourassa MG, Killip T: Use of survival analysis to determine the clinical significance of new Q waves after coronary bypass surgery. Circulation 67:302–309, 1983.

    30. 11.30 Gersh BJ, Kronmal RA, Frye RL, Schaff HV, Ryan TJ, Gosselin AJ, Kaiser GC, Killip T: Coronary arteriography and coronary artery bypass surgery: Morbidity and mortality in patients 65 or older. A report from the Coronary Artery Surgery Study. Circulation 67:483–491, 1983.

    31. 11.31 Swaye PS, Fisher LD, Litwin P, Vignola PA, Judkins MP, Kemp HG, Mudd JG, Gosselin AJ: Aneurysmal coronary artery disease. Circulation 67:134–138, 1983.

  12. 12. Program on the Surgical Control of Hyperlipidemia (POSCH)

    1. 12.1 Buchwald H, Moore RB, Varco RL: Maximum lipid reduction by partial ileal bypass: A test of the lipid-atherosclerosis hypothesis. Lipids 12:53–58, 1977.

    2. 12.2 Moore RB, Long JM, Matts JP, Amplatz K, Varco RL, Buchwald H, and the POSCH Group: Plasma lipoproteins and coronary arteriography in subjects in the Program on the Surgical Control of the Hyperlipidemias. Atherosclerosis 32:101–119, 1979.

    3. 12.3 Long JM, Brashear JR, Matts JP, Bearman JE, and the POSCH Group: The POSCH information management system: Experience with alternative approaches. J Med Syst 4:355–366, 1980.

    4. 12.4 Moore RB, Buchwald H, Varco RL, and the Participants in the Program on the Surgical Control of the Hyperlipidemias: The effect of partial ileal bypass on plasma lipoproteins. Circulation 62:469–476, 1980.

    5. 12.5 Buchwald H, Fitch L, Moore RB: Overview of randomized clinical trials of lipid intervention for atherosclerotic cardiovascular disease. Controlled Clin Trials 3:271–283, 1982.

    6. 12.6 Buchwald H, Moore RB, Matts JP, Long JM, Varco RL, Campbell GS, Pearce MB, Yellin AE, Blankenhorn CH, Holmes WL, Smink RD Jr, Sawin HS Jr and the participants in the Program on the Surgical Control of the Hyperlipidemias: A status report. Surgery 92:654–662, 1982.

    7. 12.7 Buchwald H, Moore RB, Rucker RD Jr, Amplatz K, Castaneda WR, Francoz RA, Pasternak RC, Varco RL, and the POSCH Arteriography Review Panel: Clinical angiographic regression of atherosclerosis after partial ileal bypass. Atherosclerosis 46:117–128, 1983.

  13. 13. Hypertension Prevention Trial (HPT)

    None

  14. 14. International Reflux Study in Children (IRSC)

    1. 14.1 International Reflux Study Committee: Medical versus surgical treatment of primary vesicoureteral reflux: A prospective International Reflux Study in Children. J Urol 125:227–283, 1981.

    2. 14.2 International Reflux Study Committee: Medical versus surgical treatment of primary vesicoureteral reflux. Pediatrics 67:392–400, 1981.

(*) Also in National Institutes of Health publication 82–1965, United States Department of Health and Human Services, Bethesda, Maryland.

(p.327) (p.328) (p.329) (p.330) (p.331) (p.332) (p.333) (p.334) (p.335) (p.336) (p.337) (p.338) (p.339) (p.340) (p.341) (p.342) (p.343) (p.344) (p.345) (p.346) (p.347)

(p.348)

Table B-4 Summary tabulations from sketches

Acronym and sketch no.

Item

PHS

1

UGDP

2

VA43

3

MPS

4

NCGS

5

CDP

6

AMIS

7

PARIS

8

HDFP

9

MRHT

10

CASS

11

POSCH

12

HPT

13

IRSC

14

Freq.

1. Type of trial

Therapeutic

11

Prophylactic

3

2. Type of design

Fixed sample

14

3. Stage

Initial design

0

Protocol development

0

Patient recruitment

3

Treatment and follow-up

3

Patient close—out

0

Termination

3

Post—trial follow—up

2

Completed

3

4. Funding source

NIH

12

VA

1

Industry

1

Private foundation

1

5. Funding type

Grant

8

Contract

5

Neither.

✓*

1

6. Mode of initiation

Investigator

7

Sponsor

5

Sponsor-investigator

2

7. Mode of fund dispersal

Direct to individual centers

NA

7

Indirect via a consortium award

NA

4

Direct to some centers indirect to others

NA

2

8. Funding date

Start

Sept 1981

Sept 1960

Oct 1976

Jan 1979

June 1973

Mar 1965

Oct 1974

April 1974

June 1971

June 1972

May 1973

June 1973

Sept 1981

July 1979

End

Dec 1986

April 1982

Oct 1983

Dec 1986

Oct 1983

April 1984

Nov 1979

Sept 1980

June 1985

June 1985

May 1988

Not set

Aug 1986

Not set

9. Clinics

No. in U.S. (incl P.R.)

NA

12

11

12

10

53

30

16

14

22

13

4

4

18

No. outside U.S

NA

0

0

0

0

0

0

4

0

0

1

0

0

8

Total no

NA

12

11

12

10

53

30

20

14

22

14*

4

4

26

10. Resource centers

Data coord, center

NA

NA

1

NA

1

NA

NA

NA

NA

NA

NA

NA

1

NA

3

Trt. coord, center

NA

NA

1

NA

1

NA

NA

NA

NA

NA

NA

NA

1

NA

3

Coord, center

1

1

NA

1

NA

1

1

1

1

1

1

1

NA

1*

11

Project office

1

1

1

1

1

1

1

0

1

1

1

1

1

1*

13

Central laboratories

1

2

2

0

2

1

1

1

1

I

0

1

1

0

11

Reading centers

0

1

0

1

3

1

1

1

1

2

1

2

1

2*

12

Quality control center

0

0

0

0

0

0

0

1

0

1

0

0

0

0

2

Procurement and distribution center

0

0

1

0

0

1

1

1

1

1

0

0

0

0

6

Total no

3

4

6

3

8

5

5

5

5

7

3

5

5

4*

14

11. Coord. center or data coord. center a. Location

School of public health

4

School of medicine

7

Other teaching inst

1

Nonteaching inst

2

b. Primary degree of director

MD (Epi)

PhD (Bio)

PhD (Bio)

MSc (Bio)

ScD (Bio)

PhD (Bio)

PhD (Bio)

MD (Epi)

ScD (Bio)

PhD (Bio)

PhD (Bio)

EdD (Bio)

PhD (Bio)

MD (Med)

11 Bio

c. Affiliation with other study centers

Yes

NA

✓*

✓*

✓*

✓*

5

No

NA

8

12. Type of treatment design

Noncrossover

14

13. Type of treatment structure

Simple

11

Partial factorial

2

Full factorial

1

14. Study treatments

No. of test treatments

3

3

1

2

2

5

1

2

1

1

l

1

4

1

No. of control treatments

1

2

1

1

1

1

1

1

1

1

l

1

1

1

Total no. of study trts

4

5

2

3

3

6

2

3

2

2

2

2

5

2

15. Type of test treatment

Drug.

9

Surgery

4

Behavior change

2

16. Type of control treatment

Placebo pills

7

Standard med. trt

6

No treatment

3

17. Level of in. masking

None

8

Single-masked

0

Double-masked

7

18. Patients studied

Males

14

Females

10

Children

1

Adults

13

19. Patient recruitment

a. Primary mode of contact

Direct

10

Indirect

7

b. Start of enrollment

Mid 1982

Feb 1961

Mar 1977

Mar 1979

Sept 1976

Mar 1966

May 1975

April 1975

Feb 1973

Nov 1973

Aug 1975

Sept 1975

Sept 1982

Jan 1980

c. End of enrollment

Mid 1983

Feb 1966

May 1980

Not set

June 1978

Oct 1969

Aug 1976

Sept 1976

May 1974

Feb 1976

May 1979

June 1983

Oct 1983

Not set

d. Total no, enrolled.

17,350

1,027

231

756

916

8,341

4,524

2,026

10,940

12,866

780

838

235

260*

20. Method of randomization

a. Type

Fixed allocation ratio

13

Number adaptive

1

b. Stratification variables

Clinic

NA

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

13 Yes

Disease state or type

No

No

Yes

Yes

No

Yes

No

No

Yes

No

Yes

Yes

No

Yes

7 Yes

Demographic characteristics

Yes Age

No

No

No

No

No

No

No

No

No

No

No

No

Yes Age, sex

2 Yes

Other

No

No

No

No

No

No

No

No

No

No

No

Yes*

Yes Wt

No

2 Yes

c. Total no. of variables controlled.

1

1

2

2

1

2

1

1

2

1

3

4

2

4*

d. Total no. of allocation strata.

7

12

20

36

10

106

30

20

42

22

66

48

8

216*

e. Allocation ratio

Uniform

Non-uni

Uniform

Uniform

Uniform

Non-uni

Uniform

Non-uni

Uniform

Uniform

Uniform

Uniform

Uniform

Uniform

11 Uni

f. Blocking in strata

Yes

13

No

1

g. Locus of control

Central

13

Local

1

h. Method of release

From control center to clinic via phone

✓*

7

From control center to clinic via sealed schedule

✓*

3

From clinic via selfadministered schedule

1

From clinic via on-site micro-computer

1

From control center direct to patient

1

21. Data collection schedule

a. Baseline clinic visits

NA*

2

2

1

2

3

3

2

2

3

1

2

3

1–2

b. Regular follow-up clinic visits/year

NA*

4

4

2

3–6*

3

3

3

0–3*

1*

2

1

2

1

22. Length of follow-up (yrs.)

a. During trial

4.5

9.5–14.5

3–6

2+

2

5–8

3–4+

3–4+

5–6.5

6–8

4–8

≥5

≥2

Not set

b. Post-trial

NA

2

NA

NA

NA

6+

None done

None done

3

2–4

NA

NA

NA

NA

23. Primary outcome

Deaths all causes

8

Deaths from specified cause

2

Other

✓*

✓*

✓*

✓*

4

24. Method of follow-up close-out

Common calendar date

10

Common period of follow—up

1

Not yet specified

3

25. Data entry

a. Primary entry site

CC or data CC

12

Clinic

2

b. Primary mode of entry

Direct from forms

14

Indirect from code sheets prepared from forms

0

26. Sample size specification

a. Original recruitment goal (all trts. combined)

21,500

1,000

456

522*

900

8,379

4,250

2,000

10,500

11,000

1,500

1,000

800

250*

b. Rationale for original recruitment goal

Sample size calculation

11

Pragmatic

3

c. Achieved sample size

All trts. combined

NA

1,027

231

236*

916

8,341

4,524

2,026

10,940

12,866

780

NA

NA

NA

d. Published rationale for achieved

Not applicable

6

None required

1

None stated

0

Power calculation

4

Sample size calculation

4

Pragmatic

1

27. Committees represented

Steering committee

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

14 Yes

Executive committee

No

Yes

Yes

No

No

No

No

No

No

Yes

Yes

No

Yes

No

5 Yes

Treatment effects moni toring committee

Yes

No

NA

Yes

Yes

Yes

NA

Yes

Yes

NA

NA

Yes

Yes

Yes

9 Yes

Advisory review committee

No

Yes

NA

No

Yes

Yes

NA

Yes

Yes

NA

NA

Yes

Yes

No

7 Yes

Advisory review & treatment effects monitoring comm

NA

NA

Yes

NA

NA

NA

Yes

NA

NA

Yes

Yes

NA

NA

NA

4 Yes

No. of other committees

2

10

2

1

7

11

8

1

8

8

4

3

3

0

Total no. of committees

4

13

5

3

10

14

10

4

11

11

7

6

6

2

28. Steering committee

a. Chairman

i. Primary degree

MD

MD

MD

MD

MD

MD

MD

MD

MD

MD

MD

MD

MD

MD

14 MD

ii. Patient care responsibilities

No

Yes

No

Yes

No

No

No

No

Yes

No

No

Yes

Yes

Yes

6 Yes

iii. Elected or appointed

Self-appt

E

E

Self-appt

Self-appt

Appt

Appt

Appt

E

Appt

Appt

Self-appt

E

E

5 E

iv. Term of office

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

b. Vice-chairman

i Primary degree

MPH

NA

NA

NA

NA

MD

MD

MD

MD

MD

NA

NA

MD

MD

1 MD

ii. Patient care responsibilities

No

NA

NA

NA

NA

Yes

Yes

Yes

No

No

NA

NA

Yes

Yes

6 Yes

iii. Elected or appointed

Appt

NA

NA

NA

NA

Appt

Appt

E

E

Appt

NA

NA

E

E

4 E

iv. Term of office

B. Sketches of selected trials

NA

NA

NA

NA

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

NA

NA

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

c. Membership

i. From study centers

Voting

7

26

14

12

14

14

11

9

19

39

17

6

10

10

Nonvoting

4

1

0

0

1

0

7

0

0

0

2

0

2

0

Total

11

27

14

12

15

14

18

9

19

39

19

6

12

10

ii. From outside study centers

Voting

5

0

0

1

2

1

0

5

0

0

0

0

0

0

Nonvoting

0

0

0

0

0

0

0

1

0

0

0

0

1

0

Total

5

0

0

1

2

1

0

3

0

0

0

0

1

0

iii Total

Voting

12

26

14

12

16

15

11

11

19

39

17

6

10

10

Nonvoting

4

1

0

1

1

0

7

1

0

0

2

0

3

0

Total

16

27

14

13

17

15

18

12

19

39

19

6

13

10

d. Positions represented on committee

i. Study chairman

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

14 Yes

ii. Vice-chairman

Yes

NA

NA

NA

NA

Yes

Yes

Yes

Yes

Yes

NA

NA

Yes

Yes

8 Yes

iii. CC or data CC director

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

14 Yes

iv. Clinic directors

NA

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes*

Yes

Yes

13 Yes

v. Project officer

Yes

Yes

No

Yes

Yes

Yes

Yes

NA

Yes

Yes

Yes

No

Yes

No

10 Yes

vi. Clinic coordinators

NA

No

No

Yes

No

No

Yes

No

No

Yes

No

Yes

No

No

4 Yes

vii. Nonhealth professional

No

No

No

No

No

No

No

No

No

No

No

No

No

No

0 Yes

viii. Lay representative

No

No

No

No

No

No

No

No

No

No

No

No

No

No

0 Yes

e. No. of members elected

0

0

0

0

0

4, T

5, T

0

0

B. Sketches of selected trials

0

0

0

0

29. Treatment effects monitoring committee

a. Responsible group

Trt. effects monitoring comm

9

Advisory review & trt. effects monitoring comm

✓*

4

Steering committee

1

b. Chairman

i. Primary degree

MD (Epi)

MD (Med)

MD (Med)

PhD (Bio)

MD (Med)

PhD* (Bio)

MD (Medl

MD* (Epi)

MD (Epi)

MD (Med)

MD (Med)

MD (Epi)

PhD (Bio)

PhD (Bio)

10 MD

ii. Patient care responsibilities

No

Yes

No

No

No

No*

No

No*

No

No

No

No

No

No

1 Yes

iii Elected or appointed

Appt

E

E

Appt

Appt

Appt*

Appt

Appt*

E

Appt

Appt

Appt

E

Appt

10 Appt

iv Term of office

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials*

B. Sketches of selected trials

B. Sketches of selected trials*

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

B. Sketches of selected trials

c. Vice-chairman

Primary degree

NA

NA

NA

NA

NA

MD* (Epi)

NA

MD* (Epi)

NA

NA

NA

NA

NA

NA

2 MD

Patient care responsibilities

NA

NA

NA

NA

NA

No*

NA

No*

NA

NA

NA

NA

NA

NA

2 No

Elected or appointed

NA

NA

NA

NA

NA

Appt*

NA

Appt*

NA

NA

NA

NA

NA

NA

2 Appt

Term of office

NA

NA

NA

NA

NA

B. Sketches of selected trials*

NA

B. Sketches of selected trials*

NA

NA

NA

NA

NA

NA

B. Sketches of selected trials

d. Membership

i. From study centers

Voting

1

26

0

0

0

11

0

5

5

0

2

0

7

0

Nonvoting

1

1

4

6

7

0

1

0

2

2

0

2

0

4

Total

2

27

4

6

7

11

1

5

7

2

2

2

7

4

ii. From outside study

Voting

3

0

4

5

5

5

7

3

6

7

11

8

0

4

Nonvoting

0

0

0

0

0

0

0

1

0

0

0

1

0

0

Total

3

0

4

5

5

5

7

4

6

7

11

9

0

4

iii. Total

Voting

4

26

4

5

5

16

7

8

11

1

13

8

7

4

Nonvoting

1

1

4

6

7

0

1

1

2

2

0

3

0

4

Total

5

27

8

11

12

16

8

9

13

9

13

11

7

8

e. Positions represented on committee

i. Study chairman

No

Yes

Yes

Yes

Yes

Yes

Yes*

Yes

Yes

Yes*

Yes

Yes

Yes

Yes

13 Yes

ii. Vice-chairman

No

NA

NA

NA

NA

Yes

No

No

Yes

Yes*

NA

NA

Yes

Yes

5 Yes

iii. CC or data CC director,

No

Yes

Yes

Yes

Yes

Yes

Yes*

Yes

Yes

Yes*

Yes

Yes

Yes

Yes

13 Yes

iv. Clinic directors

NA

Yes

No

Yes*

No

Yes*

No

No

Yes

No

No

No

Yes

Yes

6 Yes

v. Project officer

Yes

Yes

Yes

Yes

Yes

Yes

Yes

NA

Yes

Yes

Yes*

Yes

Yes

Yes

13 Yes

vi. Clinic coordinator

NA

No

No

No

No

No

No

No

No

No

No

No

No

No

0 Yes

vii. Nonhealth professional,

No

No

No

Yes

No

No

No

No

No

No

Yes

No

No

No

2 Yes

viii. Lay representative

No

No

No

NA

No

No

No

No

Yes

No

No

No

No

No

1 Yes

f. No. of members elected

0

0

0

0

0

0

0

0

0

0

0

0

0

0

g. Meetings per year.

2

2

2

2

2

2

2

2

2

2

2

3

2

2

30. Type of communications model

Sponsor directive

4

Sponsor nondirective

10

31. Study publications

a. No of publications

0

10

0

1

11

29

3

2

24

10

31

7

0

2

130

b. Method of authorship

Papers with corporate format alone

0

8

0

1

0

29

1

2

6

2

0

0

0

2

51

Papers with conventional format alone

0

2

0

0

3

0

1

0

8

8

29

3

0

0

55

Papers with both formats

0

0

0

0

8

0

1

0

10

0

2

4

0

0

24

32. Author participation in trial

None

4

Member of CC

3

Member of trt. monitoring or advisory review committee

7

33. Date sketch completed.

Mar 1983

April 1983

April 1983

May 1983

Mar 1983

April 1983

Mar 1983

Mar 1983

May 1983

May 1983

Mar 1983

May 1983

Mar 1983

Mar 1983

  1. (Item 5)

    • () (VA 43) Technically, VA Cooperative studies are part of the VA intramural research program.

  2. (Item 9)

    • () (CASS) Fourteen clinics participated in the registry component of the study. However, only 10 of the clinics randomized patients.

  3. (Item 10)

    • () (1RSC) The structure involves separate data centers for the United States and European portions of the study. The two centers feed results to the study coordinating center located in Germany. The project office noted is for the United States portion of the study. The European portion has no corresponding office. The two reading centers are for X-ray determination of reflux grade and renal scarring. One center reads films generated by U.S. clinics and the other center reads films generated by the European clinics.

  4. (Item 11.c)

    • () (NCGS) The data coordinating center receives its funding via a consortium award to the institution housing the study chairman.

    • () (PARIS) Coordinating center also responsible for dispersing funding to participating clinics.

    • () (POSCH) Coordinating center receives its funding via consortium award to the chairman of the study (also director of the Minnesota clinic).

    • () (HPT) Data coordinating center funds the central laboratory and food coding center of the HPT.

    • () (IRSC) Institution housing the coordinating center also houses a clinic in the study.

  5. (Item 19.d)

    • () (IRSC) Grade IV reflux patients.

  6. (Item 20. b)

    • () (POSCH) Cholesterol level and plasma lipoprotein type was used for stratification, in addition to clinic and level of coronary vessel disease.

  7. (Item 20. c and 20. d)

    • () (IRSC) The two halves of the study used different stratification procedures. The number recorded is for the U.S. portion of the study. It used clinic (18), age (3 levels), sex, and renal scarring (2 levels), creating a potential for 216 allocation strata.

  8. (Item 20.h)

    • () (IRSC) Method of release via phone for U.S. portion and via sealed envelope for European portion.

  9. (Item 21.a and 21. b)

    • () (PHS) No clinic visits required (see abstract summary in Table B–2).

  10. (Item 21. b)

    • () (NCGS) Visits at 1,2, and 3 months after randomization for dosage adjustment and data collection and at 6, 9, 12, 16, 20, and 24 months after randomization for regular follow-up visits.

    • () (HDFP) Stepped care patients seen at least once every four months. Referred care patients seen at the end of 1, 2, 4, and 5 years of follow-up.

    • () (MRFIT) Participants assigned to special intervention visited the clinic on a regular basis for administration of the required interventions. All participants seen once per year for outcome assessment.

  11. (Item 23)

    • () (MPS) Vision change using a standard visual acuity test.

    • () (NCGS) Gallstone dissolution.

    • () (HPT) Blood pressure change.

    • () (IRSC) Renal growth and scarring.

  12. (Item 26. a)

    • () (MPS) Stated recruitment goals: 522 in SMD argon trial, 736 in HISTO argon trial, and 212 in SMD krypton trial. No goal set for INVM in the argon trial or for INVM or HISTO in the krypton trial.

    • () (IRSC) Goal for reflux grade IV patients. No goal set for grade III.

  13. (Item 26. c)

    • () (MPS) The only trial with published results at the time the sketch was completed.

  14. (Item 28.d.iv)

    • () (POSCH) The chairman of the study is the only clinic director represented.

  15. (Item 29.a)

    • () (MRFIT) Originally the study had separate advisory-review and treatment effects monitoring committees. The latter committee was disbanded in 1977. Its functions were assumed by the advisory-review committee at that time.

  16. (Item 29. b and 29. c)

    • () (CDP) The treatment effects monitoring committee was headed by co-chairmen. See items 29.b and 29.c for information on the two individuals.

    • () (PARIS) The treatment effects monitoring committee was headed by co-chairmen. See items 29.b and 29.c for information on the two individuals.

  17. (Item 29.e)

    • () (MPS) The clinic director represented on the committee was also chairman of the study.

    • () (CDP) The only clinic director represented on the committee was also the vice-chairman of the study.

    • () (AMIS) The study chairman and director of the coordinating center attended meetings of the committee, but were not official members of the committee.

    • () (MRFIT) The chairman and vice-chairman of the study and the director of the coordinating center were present at meetings of the committee, but were not official members of the committee.

    • () (CASS) The project officer was present at meetings of the committee, but was not an official member of the committee.

(p.349) (p.350) (p.351)

(p.352)

Table B-5 Sample sketch for the UGDP

  1. 1. General

    1. a. Official name: University Group Diabetes Program

    2. b. Official acronym: UGDP

    3. c. Sketch number: 2

    4. d. Type of trial: Therapeutic

    5. e. Type of design: Fixed sample size design

    6. f. Stage: Completed

  2. 2. Funding

    1. a. Source: Public: National Institute of Arthritis, Metabolism and Digestive Diseases (now the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases), Bethesda, Maryland

    2. b. Type: Grant

    3. c. Mode of initiation: Investigator-initiated

    4. d. Mode of fund dispersal to centers: Direct

    5. e. Start of funding: September 1960

    6. f. End of funding: April 1982

  3. 3. Clinics: 12 (including one in Puerto Rico)

  4. 4. Resource centers

    1. a. Types of centers represented

      • Coordinating center

      • Reading center

      • Central laboratories (2)

    2. b. Coordinating center

      • Study name: Coordinating Center (Baltimore)

      • Director: Genell Knatterud, Ph.D. (Christian R. Klimt, M.D., Dr. P.H., through 1977)

      • Affiliations with other centers: None

      • Address: University of Maryland, School of Medicine, Baltimore, Maryland

    3. c. Reading center

      • Study name: ECG Reading Center

      • Director: Henry Blackburn, M.D. (Cardiology)

      • Affiliations with other centers: Lipid Laboratory and ECG Reading Center both under the direction of Henry Blackburn. There was a clinic at Minnesota as well, but it was organizationally and administratively independent of these two resource centers.

      • Address: University of Minnesota, School of Public Health, Minneapolis, Minnesota

    4. d. Central Laboratory

      • Study name: Lipid Laboratory (Minnesota)

      • Director: Henry Blackburn, M.D. (Cardiology)

      • Affiliations with other centers: Lipid Laboratory and ECG Reading Center both under the direction of Henry Blackburn. There was a clinic at Minnesota as well, but it was organizationally and administratively independent of the two resource centers.

      • Address: University of Minnesota, School of Public Health, Minneapolis, Minnesota

    5. e. Central laboratory

      • Study name: Lipid Laboratory (Morgantown)

      • Director: Margaret J. Albrink, M.D. (Medicine)

      • Affiliations with other centers: None

      • Address: West Virginia University Medical Center, Morgantown, West Virginia

  5. 5. Project office

    • Study name: Liaison Office

    • Project Officer: Keatha K. Krueger, Ph.D.

    • Affiliations with other centers: None

    • Address: National Institute of Arthritis, Metabolism, and Digestive Diseases (now the National Institute of Arthritis, Diabetes, Digestive, and Kidney Diseases), Bethesda, Maryland

  6. 6. Treatments

    1. a. Type of treatment design: Noncrossover

    2. b. Type of treatment structure: Simple

    3. c. Test treatments

      1. i. Number: 3

      2. ii. Mode of intervention: Drug

      3. iii. Treatment description: See abstract summary

    4. d. Control treatments

      1. i. Number: 2

      2. ii. Type of treatment administered: Placebo pills or capsules, or standard dose of insulin via injections

      3. iii. Treatment description: See abstract summary

    5. e. Level of masking: Oral hypoglycemic agents administered double-masked. Two insulin treatments administered in unmasked fashion.

  7. 7. Patient characteristics

    1. a. Eligibility criteria: Adult-onset diabetes diagnosed within 12 months prior to enrollment.

    2. b. Demographic characteristics: 20–79 years of age at entry. Mean age: 52.7, 71% female, 54% white.

  8. 8. Patient recruitment

    1. a. Mode of initial patient contact: Direct from primary care clinics

    2. b. Start of patient enrollment: February 1961

    3. c. End of patient enrollment: February 1966

    4. d. Total number of patients randomized: 1,027

  9. 9. Method of randomization

    1. a. Type: Fixed allocation ratio

    2. b. Stratification variable: Clinic

    3. c. Total number of allocation strata: 12 (1 per clinic)

    4. d. Allocation ratio: 1:0:1:1:1 for TOLB, PHEN, ISTD, IVAR, and PLBO, respectively, for 6 clinics not administering phenformin and for first 32 patients in the Boston clinic. Ratio of 1:3:1:1:1 was used in the 5 clinics using phenformin and after enrollment of the 32nd patient in the Boston clinic.

    5. e. Blocking constraints: After every 16th allocation for the 1:0:1:1:1:1 allocation ratio and after every 14th allocation for the 1:3:1:1:1 allocation ratio.

    6. f. Locus of control: Central

    7. g. Method of release: Coordinating center, usually via telephone. By letter if time permitted.

  10. 10. Data collection schedule

    1. a. Baseline: 2 examinations about 1 month apart

    2. b. Follow-up: Examinations at 3-month intervals after enrollment

    3. c. Post-trial follow-up: Some by individual clinics (see reference citation 2.10, Table B–3, for details)

  11. 11. Length of patient follow-up

    1. a. During the trial: Minimum: 9.5 years. Maximum: 14.5 years.

    2. b. Post-trial: 2 years. See comment for item 10.c.

  12. 12. Outcome

    1. a. Primary: Death

    2. b. Secondary: Nonfatal vascular complications, especially those affecting the eyes, heart, kidney, or peripheral vascular system.

  13. 13. Treatment effects monitoring

    1. a. Frequency: Twice a year in conjunction with semiannual investigator meetings.

    2. b. Approach: Data reports prepared by the coordinating center; reviewed by investigative group.

  14. 14. Method of close-out:

    Common close-out date. Close-out examinations performed over a 3-month period, with separation completed by August 1975.

  15. 15. Data entry

    1. a. Site of entry: At the coordinating center

    2. b. Primary mode of entry: Direct from the data forms

  16. 16. Sample size specification

    1. a. Original recruitment goal: 200 per treatment group

    2. b. Rationale for the original recruitment goal: Pragmatic

    3. c. Achieved sample size: 200+ per treatment group. Total of 1,027 patients assigned to the 5 treatment groups.

    4. d. Published rationale for achieved sample size: Power argument as stated in reference citation 2.10, Table B–3.

  17. 17. Organizational structure

    1. a. Committees

      1. i. Key committees

        • Steering Committee

        • Executive Committee

        • Advisory-Review Committee

      2. ii. Standing subcommittees of the Steering Committee

        • Analysis Coordination Committee

        • Eye Committee

        • Heart Committee

        • Kidney Committee

        • Medical Technology and Quality Control Committee

        • Mortality Committee

        • Peripheral Vascular and Neurological Committee

        • Statistical Committee

        • Clinic Review Committee

        • Editorial Review Committee

    2. b. Steering Committee

      • Name: Investigative Group

      • Chairman: Max Miller, M.D., Case-Western Reserve University, Cleveland, Ohio

      • Affiliations with other centers: Director of one of the clinics in the trial.

      • Number of members: 26

      • Membership representation: 2 voting members from each of the 12 clinics and the coordinating center.

    3. c. Executive Committee

      • Name: Executive Committee

      • Chairman: Max Miller, M.D., Case-Western Reserve University, Cleveland, Ohio

      • Affiliations with other centers: Director of one of the clinics in the trial.

      • Number of members: 9

      • Membership representation: Study chairman, director of the coordinating center, plus 2 other coordinating center representatives, plus 3 elected members from the study clinics (3-year terms), the project officer, and the chairman of the advisory-review committee.

    4. d. Advisory-Review Committee

      • Name: Advisory-Review Board (appointed in 1971)

      • Chairman: Thomas Chalmers, M.D., Mount Sinai School of Medicine, New York, New York

      • Affiliations with other centers: None

      • Number of members: 9

      • Membership representation: Members appointed by the National Institute of Arthritis, Metabolism, and Digestive Diseases without term. Members included study chairman and director of the coordinating center. No other member had any affiliation with the trial.

  18. 18. Study publications

    1. a. Number of papers published: 10 (See Table B–3)

    2. b. General method of authorship: Corporate, with writing committee indicated.

  19. 19. Information sources used for completion of sketch

    • Published papers

    • UGDP manual of operations

  20. 20. Author’s involvement in trial

    • Deputy director of coordinating center from start of study to mid-1979

  21. 21. Person reviewing sketch

    • Name: Genell L. Knatterud, Ph.D.

    • Position in study: Director of Coordinating Center

  22. 22. Date sketch completed

    April 12, 1983

(p.353)

(p.354)

Table B-6 Data coordinating centers for multicenter trials referenced in this book

Study name and acronym

Data coordinating center director

Address

1. Anturane Reinfarction Trial (ART)

Sidney H. Kane, M.D.

Ciba-Geigy Corporation

Pharmaceutical Division

Summit, New Jersey 07901

2. Aspirin Myocardial Infarction Study (AMIS)

William F. Krol, Ph.D.

Maryland Medical Research Institute

600 Wyndhurst Avenue

Baltimore, Maryland 21210

3. Beta Blocker Heart Attack Trial (BHAT)

C. Morton Hawkins, Sc.D.

School of Public Health

University of Texas

1100 Holcombe Blvd.

Houston, Texas 77025

4. Coronary Artery Surgery Study (CASS)

Lloyd D. Fisher, Ph.D.

School of Public Health

University of Washington

1107 NE45th Street

Seattle, Washington 98105

5. Coronary Drug Project (CDP)

Paul L. Canner, Ph.D.

School of Medicine

University of Maryland

600 Wyndhurst Avenue

Baltimore, Maryland 21210

6. Diabetes Control and Complications Trial (DCCT)

John M. Lachin, Sc.D.

Department of Statistics

The George Washington University

7979 Old Georgetown Road

Bethesda, Maryland 20814

7. Diabetic Retinopathy Study (DRS)

Genell L. Knatterud, Ph.D.

School of Medicine

University of Maryland

600 Wyndhurst Avenue

Baltimore, Maryland 21210

8. Early Treatment of Diabetic Retinopathy Study (ETDRS)

Genell L. Knatterud, Ph.D.

School of Medicine

University of Maryland

600 Wyndhurst Avenue

Baltimore, Maryland 21210

9. Eastern Cooperative Oncology Group (ECOG)

Marvin Zelen, Ph.D.

School of Public Health

Harvard University

44 Binney Street

Boston, Massachusetts 02115

10. Hypertension Detection and Follow-Up Program (HDFP)

C. Morton Hawkins, Sc.D.

School of Public Health

University of Texas

1100 Holcombe Blvd.

Houston, Texas 77025

11. Hypertension Prevention Trial (HPT)

Curtis L. Meinert, Ph.D.

School of Hygiene and Public Health

The Johns Hopkins University

615 North Wolfe Street

Baltimore, Maryland 21205

12. International Mexilitene Placebo Antiarrhythmic Coronary Trial (IMPACT)

Jean-Pierre Boissel, M.D.

Dept. Unite de Pharmacologie Clinique

Hopital Cardiologique

B.P. Lyon Montchat

69394 Lyon Cedex 3

France

Christian R. Klimt, M.D.

Maryland Medical Research Institute

600 Wyndhurst Avenue

Baltimore, Maryland 21210

13. International Reflux Study in Children (IRSC)

Tytti Tamminen, M.D.

University Children’s Hospital

Hufelandstrabe 55

Essen, West Germany D-4300

Robert Weiss, M.D.

Albert Einstein

College of Medicine

1825 Eastchester Road

New York, New York 10461

14. Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT)

O. Dale Williams, Ph.D.

School of Public Health

University of North Carolina

Chapel Hill, North

Carolina 27514

15. Macular Photocoagulation Study (MPS)

Barbara S. Hawkins, M.Sc.

The Wilmer Ophthalmology Institute

The Johns Hopkins University

550 North Broadway

Baltimore, Maryland 21205

16. Multicenter Investigation for Limiting Infarction Size(MILIS)

W. Kenneth Poole, Ph.D.

Research Triangle

Institute Research Triangle Park, North Carolina 27709

17. Multiple Risk Factor Intervention Trial (MRFIT)

Marcus O. Kjelsberg, Ph.D.

School of Public Health

University of Minnesota

Minneapolis, Minnesota 55455

18. National Cooperative Dialysis Study (NCOS)

Edmund G. Lowrie, M.D.

School of Public Health

Harvard University

721 Huntington Avenue

Boston, Massachusetts 02115

19. National Cooperative Gallstone Study (NCOS)

John M. Lachin, Sc.D.

Department of Statistics

The George Washington University

7979 Old Georgetown Road

Bethesda, Maryland 20814

20. Persantine Aspirin Reinfarction Study (PARIS)

Christian R. Klimt, M.D., Dr. P.M.

Maryland Medical Research Institute

600 Wyndhurst Avenue

Baltimore, Md 21210

21. Physicians’ Health Study (PHS)

Charles Hennekens, M.D.

Department of Medicine

Harvard Medical School

55 Pond Avenue

Boston, Massachusetts 02146

22. Program on the Surgical Control of Hyperlipidemia (POSCH)

John M. Long, Ed.D.

School of Medicine

University of Minnesota

Minneapolis, Minnesota 55455

23. University Group Diabetes Program (UGDP)

Genell L. Knatterud, Ph.D.

School of Medicine

University of Maryland

600 Wyndhurst Avenue

Baltimore, Maryland 21210

24. Veterans Administration Cooperative Studies Program No. 43 (VA 43)

Stephen F. Bingham, Ph.D.

Veterans Administration Medical Center

Perry Point, Maryland 20801