The prevailing divergent, empirical biomedical R&D heavily rely on statistics for variation, probability, correlation, and significance that may lead to inefficiency or high cost-effectiveness. An alternative precision/quantitative approach with Nature's biochemical, biophysical and bio-mathematical principle, leads to the unified fundamental Doctrine of the Median (DoM), that serves as the as the largest common denominator to simplify biomedical complexity and diversity. Instead of using many data points to fit the empirical curves or models, we can reversely, using only few dose data-points to fit DoM, with MAL equations, algorithms and auto-computer simulations of diagnostic plots using CompuSyn software, to achieve quantitative, automated, digitalized or indexed conclusions, in vitro, in animals and in clinical trials. Thus, experimental observations-first priority has become MAL theory-first compliance endeavor. From MAL to DoM to MAL-BD/PD/BI, took over 17 years to complete that involve the derivation of over 300 bio-reaction rate equations via the un-precedent pattern analysis, combinatory analysis and mathematical induction-and-deduction. MAL-BD/PD/BI reveals three main paradigms: (1) The Median-effect equation (MEE) as the unified theory that indicates i. Dose and Effect are interchangeable, ii. Median dose (Dm) is the universal reference point and dynamic-order common link, iii. Ki can never greater than IC50, iv. Dose-effect curves (DEC) can be linearized into straight lines, with slope (m) and x-intercept (log Dm) of the Median-effect plot (MEP), and v. The DEC can be generated via MEP with a minimum of only two data points (the MTDP theory) by computer simulation, where the 3rd point is dose-zero, and the 4th point is the universal Dm point. Thus, for data-points availability, 2 becomes 4, 3 becomes 5, and 4 becomes 6. This is a breakthrough for in vivo study/trials. (2) The Combination Index equation (CIE) where CI<1, =1, and >1 indicates, synergism, additive effect, and antagonism, respectively. (3) The Dose reduction index equation (DRIE), where DRI>1, =1, and <1, indicate favorable, no dose-reduction, and unfavorable dose-reduction, respectively, in drug combinations. The diagnostic plots provide needed BI. The terms of DoM, MEE and CIE are all dimensionless ratios, these indicating that the theory is independent to drug's physical entities (chemicals, biologicals, natural products, radiation, temperature, oxygen-tension, and pH, etc), units (ug, nM, mg/ml, mg/kg, IU, Rad, multiple of infections, etc) or mechanisms of actions (competitive, noncompetitive, uncompetitive, sequential, ordered, ping-pong, and random mechanisms). As of Jan 1, 2021, the article introduced MAL-BD/PD/BI algorithms (Chou TC, Pharmacol. Rev. 58:621-681, 2006) received 3,813 citations in 1,030 biomedical journals. In addition, the article introducing the CI algorithm and computer software (Chou TC and Talalay P. Adv. Enz. Regul. 22:27-55, 1984) received 6,937 citations in 1,338 biomedical journals globally. These confirmed the board applications to nearly all disciplines of biomedical R&D.