Table 2.

Citations of the Karlowski (1975) trial by influential researchers and documents.

Source [Ref.]	Statement
Cecil Textbook of Medicine (1996, 2000, 2004) [55,56,57]	“a variety of actually ineffective treatments have been reported to be effective due to inadequate blinding of placebo recipients. One example of this phenomenon was a study of large dose of vitamin C to prevent colds, in which many placebo recipients dropped out of the study because they could tell by tasting the medication that they were not receiving the vitamin C [Karlowski 1975]”
Principles and Practice of Infectious Diseases (1979, 1985, 1990, 1995) [58,59,60,61]	“Many participants correctly surmised from the taste of the contents of the capsules used whether they were receiving vitamin C or a placebo (Karlowski 1975)”
Textbook of Pediatric Infectious Diseases (1987, 1992, 1998) [62,63,64]	“It is most probable that the reported benefits are a result of statistical artifacts and placebo effect due to poor study design rather than specific pharmacologic drug effects [Karlowski 1975]”
Recommended Dietary Allowances, 9th ed (1980) [65]	“Karlowski et al. (1975) found that when those subjects who had guessed the nature of their medication (ascorbic acid or placebo) were eliminated from consideration, the differences between the vitamin and placebo groups were not significant”
Evolution of Evidence for Selected Nutrient and Disease Relationships (2002) [66]	“Karlowski and colleagues (1975) conducted a small, double-blind study with 311 employees of the National Institutes of Health and concluded that vitamin C had ‘at best only a minor influence on the duration and severity of colds,’ and ‘the effects demonstrated might be explained equally well by a break in the double blind.’ ”
CONSORT statement [67]	“Unblinded outcome adjudicators may differentially assess subjective outcomes…These biases have been well documented” [Karlowski (1975) as one of the references]
Cochrane Handbook (1994, 2002, 2004, 2006) [68,69,70,71]	“Some research suggests that such blinding is important in protecting against bias (Karlowski 1975) …there is evidence that participants who are aware of their assignment status report more symptoms, leading to biased results (Karlowski 1975) ...Blinding is likely to be particularly important in research with subjective outcome measures such as pain ...(Karlowski 1975)”
Fundamentals of Clinical Trials (1982,1985,1998,2010) [72,73,74,75]	“A trial of the possible benefits of ascorbic acid in the common cold started out as a double-blind study (Karlowski 1975). However, it soon became apparent that many of the participants, most of whom were medical staff, discovered whether they were on ascorbic acid or placebo…Among those participants who claimed not to know the identity of the treatment, ascorbic acid showed no benefit over placebo. In contrast, among participants who knew or suspected what they were on, ascorbic acid did better than placebo. Therefore preconceived notions about the benefit of a treatment, coupled with a subjective response variable, may have yielded biased reporting.” “An evaluation such as that provided by Karlowski and colleagues for a trial of vitamin C is commendable”
Clinical Epidemiology (1986, 1996, 2006) [76,77,78]	“Lack of blinding…Because a subject’s suspicion of the group to which he or she had been signed so strongly influenced the results, and because a subject’s suspicion was much more often right than wrong, the validity of the vitamin C-placebo comparison was seriously compromised [in Karlowski 1975]”
Clinical and Translational Science: Principles of Human Research (2017) [79]	“Blinding (or masking) is essential in most explanatory trials...examples of incorrect results due to bias in trials without blinding (Karlowski et al., 1975)...reinforce the value of blinding”
Principles and Practice of Clinical Research (2007) [80]	“Blinding is essential in most explanatory trials since the opportunity for bias is substantial...Despite the rarity of deceit in clinical research, examples of incorrect results due to bias in trials without blinding (Karlowski 1975) …reinforce the value of blinding”
BMJ (1976) [81]	“American study of adult employees of the National Institutes of Health reported in 1975 found no significant prophylactic or therapeutic benefit from ascorbic acid”