STAR trial

STAR trial (Study of tamoxifen and raloxifene), which was completed in 2006, demonstrated additional utility of raloxifene in the prevention and treatment of breast cancer. In fact, the absence of associated uterotrophic effects with raloxifene suggests that it may be a safer agent than tamoxifen for use as a chemopreventative in high-risk postmenopausal women [3] therefore, raloxifene has very recently become a new option for breast cancer prevention now available for physicians and their patients. 

Wickerham DL (2003) Tamoxifen s impact as a preventive agent in clinical practice and an update of the STAR trial. Recent Results Cancer Res 163 87-95... 

Chappie CR et al A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome Results of the STAR trial. Eur Urol 2005 48 464. [PMID 15990220]... 

Further demonstration of the utility of raloxifene in the prevention of breast cancer came from the STAR trial (Study of Tamoxifen and Raloxifene), which followed more than 19,000 post-menopausal women for 5 years. This was a prospective, doubleblind, randomized trial comparing 20 mg/day tamoxifen versus 60 mg/day raloxifene, which resulted in the demonstration that incidence rates of invasive breast cancer for both treatments were comparable.39... 

Rush, A. J., Fava, M., Wisniewski, S. R. et al. (2004). Sequenced treatment alternatives to relieve depression (STAR D) rationale and design. Controlled Clinical Trials, 25(1), 119-42. 

CLINICAL PRACTICE VERSUS CLINICAL TRIALS THE STAR D TRIAL... 

Using this very strict criterion of remission, the STAR D researchers reported that 37 per cent of the patients in the trial recovered from depression on the first medication they were given. Another 19 per cent of the full group of patients recovered on the second medication, 6 per cent on the third and 5 per cent on the fourth. Altogether, 67 per cent of the patients recovered. However, the remission of symptoms turned out to be only temporary for many - approximately half of the patients who recovered relapsed within a year. 

The Oklahoma study showed the same pattern of results as the STAR D trial. Some treatments seemed to be effective for some patients and other treatments seemed effective for others. More than half of the subjects responded successfully to the first treatment 17 per cent did not respond to the first treatment, but did respond to the second. The third treatment was successful for another 20 per cent who had not responded to prior treatments, and by the time the sixth treatment was tried, 100 per cent of the subjects had successfully responded to at least one of them. 

Like the STAR D trial, this study seemed to show that different people respond to different medications and that the key might be finding the right treatment for the right person -but there was a catch. None of the medications were real treatments for nausea or vomiting. Instead, they were all placebos. 

Most clinical trials, including the ones my colleagues and I analysed, are conducted on volunteers, many of whom are recruited for the trial by advertisements. Perhaps these depressed people are not as responsive to antidepressants as the patients seen in clinical practice. The STAR D trial that I described earlier was designed specifically to evaluate the effect of antidepressants on the kinds of patients who are typically seen in clinical practice. None of the patients in this trial were recruited by advertising. Instead, they were all patients who sought treatment for depression in family practice or psychiatric out-patient treatment facilities. Also, the usual exclusion criteria were relaxed, so that a broader range of patients was evaluated. The trial did exclude patients who had already tried antidepressants but had not responded to them, although this exclusion should result in better response rates, not worse ones. 

The STAR D trial is not alone in finding that all antidepressants are created equal. In meta-analyses of head-to-head comparisons of different antidepressants, statistically significant differences are occasionally found, but these tend to be very small... 

A four-choice star maze, similar to that used by Kubie and Halpern (1978, 1979), was used as a two-choice Y maze for training the snakes. Snakes were trained to follow earthworm extract trails (IX = 6 gm earthworm per 20 ml dH20) in the apparatus until their performance exceeded chance behavior. (See Kubie and Halpern 1978 for details). At the termination of testing, snakes were videotaped during trailing at each earthworm concentration (IX, 1/9X, 1/8IX, Dry). Trials were repeated until a minimum of one minute of good, analyzable film had been obtained at each concentration. This usually involved one to three trials. For filming of animals from the side, a clear plastic maze of similar dimensions was used. 

Models of hot isentropic neutron stars have been calculated by Bisnovatyi-Kogan (1968), where equilibrium between iron, protons and neutrons was calculated, and the ratio of protons and neutrons was taken in the approximation of zero chemical potential of neutrino. The stability was checked using a variational principle in full GR (Chandrasekhar, 1964) with a linear trial function. The results of calculations, showing the stability region of hot neutron stars are given in Fig. 7. Such stars may be called neutron only by convention, because they consist mainly of nucleons with almost equal number of neutrons and protons. The maximum of the mass is about 70M , but from comparison of the total energies of hot neutron stars with presupemova cores we may conclude, that only collapsing cores with masses less that 15 M have... 

Rudolf5s trial on account of the business with Remer s version ended in summer 1995. Under which star this trial was held was made blindingly clear by a document from the trial records Rudolf s judges in the District Court of Stuttgart wanted to prevent that they themselves should come under the wheels of denunciation and inquisition, as had the judges of the District Court of Mannheim in the Gunter Deckert Case, who were massively criticized by media and politicians,... 

One form of rape often facilitated by the use of incapacitating or intoxicating drugs is termed either acquaintance rape or more commonly date rape. Date rape itself has become increasingly recognized as a real problem in our society. Indeed, the issue came to public attention in the 1990s with the advent of Court TV and the high-profile trials of Mike Tyson and William Kennedy Smith. More recently, basketball star Kobe Bryant has also made headlines in... 

Nowhere are these transitions more apparent than in the design of three important studies sponsored by the National Institute of Mental Health. One—the STAR D study—is discussed in detail in Chapter 3. The other two, the CATIE study and the STEP-BD study, are reviewed briefly here as an illustration of current trends in psychiatric research. These three studies break new ground in the sense that they go beyond the concept of efficacy that is established in the industry-sponsored studies The drug is shown to be efficacious for a certain disorder, but in the real world, will physicians prescribe it and will patients take it and stay on it The answer to these questions centers on the concept of effectiveness. An effective drug is one that not only has efficacy against a certain malady but also is accepted by patients because its safety, tolerability, mode and frequency of administration, price, taste, appearance, and so on. These issues are commonly left unexamined in the classic drug trials. 

Roos Y. Antifibrinolytic treatment in subarachnoid hemorrhage a randomized placebo-controlled trial. STAR Study Group. Neurology 2000 54(l) 77-82. 

Hemoperfusion was used for the first time as an option of treatment in a severe case by Chen LL et al [18] and patient consciousness returned to normal without subsequent mental confusion. Wu MY et al [19] submitted 2 patients with severe intoxication to 20 hours and 8 hours of hemoperfusion and also had good and fast improvement of the intoxication condition. In this 3 cases, 2 hemodialysis sessions in the first described patient, 1 hemodialysis session and 2 daily hemodialysis session in the patients of the second report failed to counterbalance neurotoxicity however consciousness improved dramatically after hemoperfusion [19]. A dramatic decrease in comatose time and rapid weaning from the ventilator may help reduce morbidity and mortality [19]. Hemoperfusion seems to be a promising kind of treatment to severe cases of star fruit intoxication. However this issue requires further analysis with large trials [19]. 

Vogel VG, Costantino JP, Wickerham DL, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes the NSABP study of tamoxifen and raloxifene (STAR) P-2 trial. JAMA 2006 295(23) 2727 L... 

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