Randomised experiments

Uncontrolled Variables and Randomization. A number of further variables, such as ambient conditions (temperature, pressure, etc), can be identified but not controlled, or are only ha2ily identified or not identified at all but affect the results of the experiment. To ensure that such uncontrolled variables do not bias the results, randomisation is introduced in various ways into the experiment to the extent that this is practical. 

The experiments were carried out between November 1982 and April 1984, in a randomised order. 

The debate about quality of evidence most frequently ranks large randomised controlled trials as the gold standard, at least for efficacy, with controlled observational studies in the middle, and imcontrolled studies and opinions at the bottom. The evaluation of therapeutic benefit and risk is, in fact, never ending because clinicians will subject marketed medicines to comparison with other existing or new medicines, and they will experiment with alternative dosage schedules and combined use with other treatments. 

A controlled clinical trial is an experiment and, as just mentioned, it deliberately alters the fabric of routine management of study subjects. It does so in two ways. First, it directs which treatment modality will be given to a particular subject, usually by randomised allocation without the doctor or subject knowing which treatment they will receive out of the two or three chosen for the trial. Therefore, a subject may not receive the conventional treatment that the clinician might otherwise have chosen. Second, the selection and... 

Fig. 14 ZK-253 effects on tamoxifen-resistant breast cancer xenograft tumours. Estrogen-dependent MCF-7/TAM tumours were implanted on day 0 into one flank of 70 estrogen-and tamoxifen-supplemented nude mice. After tumours had reached approximately 25 mm in size (after about 22 days), mice were randomised into seven groups (10 mice each) three control groups (control tamoxifen, control vehicle or control ovariectomy without estradiol), and the fom treatment groups (ZK-703, ZK-253, raloxifene or fulves-trant) each at 10 mg/kg subcutaneously daily. Treatment was continued either until the end of the experiment or imtil tumoms reached a median of approximately 100 mm (larger tumours were observed in some mice). The tumours were then removed, snap frozen, and used for analysis of ER levels, a Xenograft tumour growth curves. Data are expressed as medians with interquartile ranges, b ERa levels. Data are expressed as mean with upper 95% Cl...

The randomised part of the Salk Polio Vaccine trial has all the hallmarks of modern day trials randomisation, control group, blinding and it was experiences of these kinds that helped convince researchers that only under these conditions can clear, scientifically valid conclusions be drawn. 

Other problems pointed out by Box et al. [20] are serially correlated errors, dynamic relations and feedback. All the above problems can be overcome by the use of properly designed statistical experiments that employ features such as randomisation, blocking and other suitable controls. 

There has been discussion of late of the rather fine point that, strictly speaking, shape is not a property of molecular potential energy eigenstates [934]. It has been suggested that hydrogen randomisation is a sort of consequence of this fact, due to the hydrogen atoms in hydrocarbon ions being delocalised over a set of potential wells [204]. At the level of approximation appropriate for the explanation of the results of current mass spectrometric experiments, however, molecules can be said to have shape. 

The assembly of molecular ions formed in a mass spectrometry experiment typically contains ions with different amounts of internal energy. A distribution function P( ) can be defined, provided internal energy is randomised and reaction is slow compared with the ionization and randomisation processes. P( ) must be appropriately normalised. It will be assumed here that /fmax P(E)dE is equal to the total number (per time) of molecular ions formed without restriction as to internal energy content. For a single decomposition, eqn. (3) becomes... 

In the reaction F + C6D6, it appears that the distribution of energy is random when attention is focused on the C6DSF vibrational distribution measured in infrared chemiluminescence experiments [583], but is non-random for the product recoil distribution measured in a molecular-beams experiment [588]. This could be rationalised if certain modes in the complex do not take part in the randomisation or if a few specific modes are coupled to the reaction coordinate at the transition state (the exit channel barrier). 

It might, however, be more satisfactory if the order of carrying out the experiments were randomised (as they stand in Tablejf3 it is systematic, the order being A, B, C, D in each block). If there was any tendency for the firat experiment in each case to be high, then this would appear as a high result for A which would be Uacious. Randomisation, such as has been carried out in Table 1.4, would avoid this. 

Grade A, meta-analysis of randomised, controlled trials or from at least one randomised, controlled trial, or from at least one well designed, controlled study without randomisation grade B, from at least one other type of well designed, quasi-experlmental study, or from well designed, nonexperimental studies (e.g. comparative studies, correlation studies, case-control studies) grade C, from expert committee reports/opinions and/or clinical experience of authorities, ND, not demonstrated. Data from the Royal College of Physicians and the Bone and Tooth Society. 

In reviewing this topic it is clear that most relevant studies are observational population-based studies. These studies are mainly cross-sectional and therefore they are most suitable for generating hypotheses. Some studies are hypothesis-testing clinical experiments, and there are few randomised-controlled trials or meta-analyses. Strong evidence-based recommendations for the prevention of asthma and allergy are unable to be made except for ETS. 

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