Summary Background Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti‐tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. Aim To develop evidence‐based consensus statements for TDM‐guided anti‐TNF therapy in IBD. Methods A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. Results 22/24 statements met criteria for consensus. For anti‐TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3‐8 and 5‐12 μg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints—such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision‐making. In stable clinical response, TDM‐guided dosing may avoid future relapse. Data indicate drug‐tolerant anti‐drug antibody assays do not offer an advantage over drug‐sensitive assays. Further data are required prior to recommending TDM for non‐anti‐TNF biological agents. Conclusion Consensus statements support the role of TDM in optimising anti‐TNF agents to treat IBD, especially in situations of treatment failure.

1More than a hundred equations of state relating the pressure, volume, and temperature of gases have been proposed according to Dodge ( 7 ) , but only a very few of them have attained any practical importance as the majority do not represent the data with sufficient accuracy. In this work the significant pressure-volume-temperature (hereafter referred to as P V T ) characteristics of pure gases have been examined in detail, and an equation has been developed to fit precisely the characteristics common t o different gases.PVT data may be plotted on different types of graphs, of which probably the oldest is that of pressure vs. volume with temperature as a parameter, as shown in Figure 1. From this graph van der Waals deduced two properties of the critical isotherm namely, that at the critical point the slope is zero and an inflection occurs.' Van der Waals expressed these two properties algebraically in the following well-known manner :where P is pressure, V is volume, and T is temperature, as indicated above. Van der Waals employed these two conditions to evaluate the two arbitrary constants in the equation of state he proposed.A number of other two-constant (exclusive of the gas constant) equations of state have been proposed, the best known being those of Berthelot and Dieterici. None of them, however, actually represent the PVT data over a wide range *Some investinations ( 1 3 ) indicate that the critical isothermis not the smoothly inflected curve shown in Figure 1. This result seems to be attributed to the indefiniteness of the critical state and possibly to the lack of attainment of true equilibrium.with any great degree of precision and not one of them is considered suitable for the calculation of accurate thermodynamic diagrams. This does not imply, however, that these two-constant equations have not been extremely useful. Van der Waals' equation was of the greatest value in leading to the principle of corresponding states.In one form the correspondingstate principle suggests that the compressibility factor, x = PVIRT, depends only on the reduced temperature and pressure, which are defined respectively as T , = T I T , and P,= PIP,. On a generalized compressibility chart for many different compounds single average lines are drawn for each isotherm; however, to demonstrate that the principle is approximate, Figure 2 has been constructed to emphasize the differences which actually exist among compounds.From the compressibility chart it is noted that all gases follow the ideal-gas law as the pressure approaches zero, regardless of the temperature. This may be expressed as Z = PV/RT= 1 at P = 0 for all temperatures (3) With any isotherm t,aken at Po = 0, 2, = 1.0, (dZ/dP,) = lim (2 -1) / (P, -0 ) as P, -+ 0 = lim RT (Z -I)/RTP, as P, -+ 0 = (P,/RT) Iim(ZRT/P-RT/P) (5) FIG. 1. PRESSURE-VOLUME DIAGRAM. ~ A curious corollary of this is the seemingly contradictory fact that in general V does not equal R T I P at P=O. By definition of a derivative a t any point ( P o , 2,) on the compressibility chart, ----------(...

An analysis is made of volume-cubic equations of state, starting with the most general generating equation from which all specific forms can easily be derived. One equation is shown to be both the simplest and the best in performance. A new quantity, the z-chart sum, is presented, which is a useful way to compare all equations of state, whether cubic or otherwise, while at the same time permitting excellent predictions of the second virial coefficient at the critical temperature from the critical compressibility factor. Extensive comparisons of reliable experimental PVT data with a number of equations of state are given for a wide range of substances from nonpolar to polar, and these demonstrate the superiority of the simplest two-term cubic equation.

In an earlier paper the general PVT characteristics of pure gases and liquids were presented by Martin and Hou ( I ) .The hypothesis was advanced that complete representation of the PVT behavior of any pure gas requires a knowledge of the critical temperature, pressure, and volume and of the slope of the vaporpressure curve at the critical point. Based on this hypothesis an equation of state of the following form was developed:In this expression the jtJs are temperature functions of the kind f t = A ; + 3,T (2) Although it was desirable to evaluate all the constants, it did not prove possible at the time; therefore A, C,, Bd, CI, A , and Cg were set equal to zero, and B1 was set equal to R so that proper behavior would be obtained a t infinite attenuation (that is, ideal-gas state). The expanded form of the original equation isand the constants are evaluated from formulas derived from the general PVT characteristics and the basic hypothesis. The derivations of these formulas are presented in the original paper (1). THE MODIFICATIONSince its original development six years ago, the equation of state has been applied to a number of compounds. In some cases only the minimum four facts (Pc, T,, V,, and m, the slope of the vapor-pressure curve at the critical) were employed to get the equation constants. In other cases the equation was fitted to the actual data by adjusting constants. To understand the new modification, it is desirable to know how the equation is fitted to the data for a given gas. When one refers to an isometric plot such as shown in the accompanying figure, the first step consists in obtaining the temperature functions along the Vol. 5, No. 2 critical isotherm. In this procedure the data are fitted with extremely high precision at the critical temperature to a density of about 1.5 times the critical density. The critical isometric is then fitted exactly from the critical point to the highest temperature to which it extends as a straight line. For all ordinary substances this is the highest temperature encountered in practical use.* Next, by means of the Boyle point temperature, the data are fitted at high temperature and low density. By means of the T' temperature the data are fitted a t low temperature and low density.For densities a little over the critical and temperatures above the critical there was no actual fitting operation even when data were available. Comparison of the equation with the experimental data in this region, which is circled in the figure, showed, however, that the isometrics predicted by the equation curved upward a little too much. This was true for a wide variety of gases. To correct this curvature of the higher density isometrics, recourse was made to two additional properties that are common to all gases. As pointed out in the original paper, the isometrics at about 1.5 to 2.0 times the critical density tend t o be straight, just as a t the critical density. Mathematically this means that(dZP/dTZ). = 0 at V = V J n (4) where n lies between 1.5 and 2.0. The slope of this is...

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