Clinical Studies

World-wide more than40 clinical studies involving over 5,500 patients have been conducted to evaluate the consistency, reproducibility, optimal dose, performance, safety, efficacy, and clinical relevance of TRUE TEST® (Allergen Patch Test). TRUE TEST® has been shown consistently to provide a safe, effective, clinically relevant method of diagnosing ACD (Allergy Contact Dermatitis). Reference 12

Consistency and reproducibility

TRUE TEST® has been tested clinically for consistency and reproducibility in several studies.12 In each study, three separate production lots of allergens were evaluated for uniform reactivity. All patients had previously confirmed allergy to the test allergens.

In one study of 39 patients, three production batches of nickel sulfate, ethylenediamine dihydrochloride, and epoxy resin produced similar positive results in 90% to 100% of reactions. 12 There were two discordant reactions in patients with known nickel sensitivity. One patient sensitized to nickel sulfate showed two strong (++) reactions to two batches and a negative (-) reaction to batch No. 3. The second evaluator made the same interpretation. A second nickel-sensitive patient had a weak (+) reaction to batch Nos. 2 and 3 and a negative (-) reaction to batch No. 1. In evaluating this patient, a second evaluator scored strong (++) reactions for batch Nos. 2 and 3 and a weak (+) reaction for batch No. 1. Evaluations were performed at 72, 96, or 120 hours. Reference 12

A second study was a randomized, double-blind, placebo-controlled investigation conducted with 47 patients, 42 of whom had responses. 12 Balsam of Peru, black rubber mix, Cl+ Me- isothiazolinone, and thiuram mix produced consistent positive reactions in 93% of cases (39/42), with no discordant reactions observed. The reactions were interpreted by two independent observers. The study found complete correspondence between the two evaluations for responses to all allergens evaluated. Reference 12

In a third study, also a randomized, double-blind, placebo-controlled trial, three lots of p-phenylenediamine generated consistent test reactions in 90% of patients (9/10). 12 There were no discordant reactions in this study.

Taken together, the results of these studies demonstrated good reproducibility from different production lots of allergens contained in TRUE TEST (Table 1). Reference 12,14

Table 1.- Concordance of Reactions

Dose Optimization

The optimal dose for TRUE Test® allergens has been determined through controlled clinical testing to ensure a consistent allergen dose sufficient to elicit a response, yet low enough to minimize the potential for irritation or sensitization. Reference 12

The P-phenylenediamine (PPD) patch used in TRUE Test® is in the form of the PPD base as recommended by the International Contact Dermatitis Research Group and the European Environmental Contact Dermatitis Research Group. Previously, the hydro chloride salt formulation was used.

In a controlled, dose-response and irritation study in 211 patients, the final concentration of PPD base in TRUE Test®, 0.09 mg/cm2, was determined by a dilution series of 0.20, 0.15, 0.10, and 0.05 mg/cm2 of PPD base compared to PPD hydro chloride 0.05 mg/cm2 . 12 In the 14 patients who were shown to be allergic to PPD, the 0.10 mg/cm2 dose was the minimum concentration that consistently elicited an allergic reaction with the lowest frequency of irritant reactions. In contrast, 0.05 mg/cm2 PPD hydro chloride caused positive reactions in only five patients. Reference 12

Like PPD, N-hydroxymethyl succinimide (HMS) is unique to TRUE Test®. Used in formaldehyde testing, HMS is a formaldehyde-releasing compound developed to overcome instability of native formaldehyde patches. In initial safety evaluations in nine healthy volunteers, HMS was found to be nonirritating at a concentration of 0.12 mg/cm2. In contrast, five of the nine showed irritant reactions to a concentration of 1.12 mg/cm2, and three of the nine exhibited irritant reactions to the 0.57 mg/cm2 concentration. 12 A dose-response study in 25 patients with previously confirmed formaldehyde allergy indicated that an HMS concentration of 0.16 mg/cm2 was sufficient to detect formaldehyde allergy. Reference 12

The current HMS concentration in TRUE Test®, 0.18 mg/cm2, was established in a larger dose-finding study. Of the 259 patients with suspected allergic contact dermatitis who were tested in this controlled, multicenter study, 255 were available for evaluation. Concentrations of HMS tested were equal to 0.4, 0.3, 0.2, and 0.1 mg formaldehyde/cm2. The carrier (succinimide) and the vehicle (polyvinylpyrrolidone) also were tested. For comparison, a 1% aqueous solution of formaldehyde was tested. A dose-response relationship was apparent when both positive and irritant (IR) or doubtful (?) reactions were considered. The threshold for increasing irritant reactions was 0.25 mg formaldehyde/cm2, which is well above the HMS concentration in TRUE Test® of 0.18 mg/cm2. The 0.18 mg/cm2 dose was found to elicit consistent allergic reactions with minimal irritation among the patients tested. Reference 12

General Performance and Reactivity

TRUE TEST® has been evaluated for overall performance and allergen reactivity in 422 patients in four clinical studies in the United States. Patients with suspected allergic contact dermatitis, based on history or clinical signs, were tested in all studies. Reference 14

The four clinical studies were conducted using the TRUE Test® product that contained 24 allergen patches on Panel 1 and Panel 2. In the current product, Panel 1 and 2, the configuration of the allergens has been changed. The quinoline mix allergen patch has been deleted; it has been replaced by a negative control (an uncoated polyester patch). Also, the positions of the epoxy resin and paraben mix patches have been changed on the panels. The change in allergen configuration does not affect the results of the reaction frequencies observed for TRUE Test®. Reference 14

In an open, multicenter study designed to evaluate the performance of TRUE Test® Panel 1 in a conventional clinical setting, 128 patients were screened prospectively for ACD. Positive reactions to 11 of the 12 allergens were observed in 45 patients. There were positive test reactions to all allergens except chromium. The most common allergic reactions were to nickel (n=21), fragrance mix (n=9), and cobalt dichloride (n=9). 14 As might be expected, some itching and burning sensations were reported.

In a second study, 122 patients with suspected contact dermatitis were recruited. TRUE Test® Panel 2, containing 11 allergens and a negative control, was applied to the patient’s back and remained there for 48 hours. The results were evaluated at either 72 or 96 hours. Thirty-three patients showed a total of 47 positive test reactions. There were positive test reactions to all of the allergens except quinoline mix and paraben mix. Reference 14

In a third study of 122 patients who had been referred for contact allergen testing, TRUE Test® Panel 1 and 2, containing 24 allergens, were applied to the patient’s back and remained there for 48 hours. The results were evaluated at either 72 or 96 hours after application. Results show that 71 patients had a total of 122 positive test reactions. Eleven patients demonstrated a total of 14 doubtful (?) reactions. Three patients experienced an irritant (IR) reaction. There were positive test responses to all of the allergens.

In a separate, open, multicenter, within-patient study, Panel 1 and Panel 2 were evaluated together in 50 patients with suspected contact dermatitis. Results were evaluated after 72, 96, 120, or 168 hours. Test sites also were reassessed after 21 days for late and persistent local reactions. Reference 14

A total of 66 reactions were observed in 32 patients. All allergens except caine mix, epoxy resin, and quinoline mix elicited at least one response in this group of patients. The most common reactions were to nickel sulfate (14%) and quaternium-15 (11%), followed by equal numbers of reactions to balsam of Peru, cobalt dichloride, formaldehyde, and thimerosal (8% each). Reference 14

Ten persistent local reactions were observed in eight patients at the 21-day safety visit. One of these had a late ++ reaction to Cl+ Me- isothiazolinone. Most patients (34 of 50) did not experience any itching or burning. Fourteen patients reported mild and two patients reported moderate itching or burning sensations. There were no other adverse events reported in this study. The surgical tape adhered perfectly in 45 patients (90%). Mild adhesive irritation was reported by a single patient. 14 The results of these studies suggest that the TRUE Test® standard panel is a clinically relevant method of diagnosing ACD. 14 A postmarketing survey conducted from the introduction of TRUE Test® in January 1995 through the end of December 1995 supports these clinical trial results. This survey evaluated a total of 1,772 data collection forms completed by physicians administering TRUE Test® during 1995. Reference 15

According to survey results, allergens with the highest reaction rate frequency included nickel sulfate (17.6%), quaternium-15 (11.0%), thimerosal (9.1%), and formaldehyde (9.0%). For those patients who had a positive reaction to the contact allergen test, 27% of the surveys responded to questions regarding clinical relevance. In 75.9% of these cases, the results corresponded to the patient’s contact history. Reference 15

The survey also revealed a low incidence of tape irritation (2.5%) and tape adhesion problems (3.6%). The number of adverse events reported was also very small and centered around symptomatology expected with the elicitation of an allergic reaction. Reference 15