RCT of Streptomycin Therapy for Tuberculosis

Description

Results of a randomized, placebo-controlled, prospective 2-arm trial of streptomycin 2 grams daily (arm A2) vs. placebo (arm A1) to treat tuberculosis in 107 young patients, as reported by the Streptomycin in Tuberculosis Trials Committee in 1948 in the British Medical Journal (more details available below the variable definitions).

Usage

strep_tb

Format

A data frame with 107 observations and 13 variables

patient_id

invented id number for each participant; type: character

arm

assigned treatment arm, Streptomycin or Control; type: factor

dose_strep_g

grams, dose of Streptomycin: numeric, 0, 1, or 2 grams

dose_PAS_g

grams, dose of PAS (Para-Amino-Salicylate): numeric, 5, 10, or 20 grams. Note that no one in this intial study (study A) received PAS. This was added for combination therapy in studies B and C, as reported in 1952.

gender

gender, dichotomous (this was in 1948); type: factor, with levels: M = Male, F= Female

baseline_condition

Condition of the Patient at Baseline, 3 levels, 1_Good, 2_Fair, 3_Poor; type: factor

baseline_temp

temperature at baseline in degrees fahrenheit or celsius, but categorized into 4 levels (afebrile level apparently were cases not measured with a thermometer): factor, with levels: 1_afebrile, 2_<99F/<37.2C, 3_99-99.9F/37.2-37.75C, 4_100F+/37.7C+

baseline_esr

Erythrocyte Sedimentation Rate in mm per hour, categorized into 4 levels, from 0-51+ mm per hour; type: factor, with levels: 1_0-10, 2_11-20, 3_21-50, 4_51+

baseline_cavitation

dichotomous presence of cavitation on the baseline chest x-ray; type: factor: 0_no, 1_yes

strep_resistance

streptomycin resistance after 6 months of therapy, measured on a 0-100+ scale, categorized into 3 levels - sensitive, moderate, and resistant; type: factor: 1_sens_0-8, 2_mod_8-99, 3_resist_100+

radiologic_6m

Likert score rating of radiologic response on chest x-ray at 6 months; type: factor: 1_Death, 2_Considerable_deterioration, 3_Moderate_deterioration, 4_No_change, 5_Moderate_improvement, 6_Considerable_improvement

rad_num

Likert score numeric rating of radiologic response on chest x-ray at 6 months; type: numeric: 1-6, from Death to Considerable Improvement

improved

Dichotomous outcome of improvement (equal to rad_num of 5-6); type: logical, TRUE or FALSE. 55 of the 107 participants were improved.

Details

The Streptomycin for Tuberculosis trial in 1948 was considered the first modern randomized, placebo-controlled clinical trial, which could be done in part because there were very limited supplies of streptomycin in the UK after World War II.
This publication seems a bit primitive today, without standard features like a proper Table 1, and some creative use of graphs to display baseline characteristics of the study sample
More strikingly, there is no ethics committee approval, or consent.
You can read the pdf of the original journal article at Streptomycin in TB Study.
This was the first of a series of 3 trials, in which the initial effectiveness of Streptomycin was established, but rapid resistance developed, and significant side effects occurred at a dose of 2 grams of streptomycin. This type of resistance also occurred with another new anti-tubercular therapy at the time, PAS (Para-Amino-Salicylate). Subsequent trials B and C evaluated different doses and combinations of Streptomycin and PAS, and were published together in 1952 in the BMJ, with the pdf available here 1952 Three Streptomycin in TB Studies Summarized.
Commentary on the conduct of these trials from one of the MD investigators can be found at MD Clinical Trialist Commentary.
Commentary on the design and analysis of these trials from statistician A. Bradford Hill can be found at Statistican Commentary.

Source

This data set is reconstructed to the best of my ability from the paper in the British Medical Journal from 1948, entitled, Streptomycin Treatment of Pulmonary Tuberculosis, pages 769-782 in the October 30, 1948 edition, authored by the Streptomycin in Tuberculosis Trials Committee. You can find the pdf at Streptomycin in TB.