In this article, we discuss a key difference between the traditional
framework for null hypothesis significance testing (NHST) and the
permutation framework for NHST. This critical difference lies at the
root of the framework in the specification of the null and alternative
hypothesis. First, we review the traditional approach to NHST. Second we
explain how the use of the permutation framework requires particular
care when formulating the null and alternative hypotheses. Finally, we
will discuss an approach proposed by Pesarin and
Salmaso (2010), coined **Non-Parametric
Combination** (NPC), which allows one to combine several test
statistics into a single test.

The traditional approach to NHST pertains to specifying a null distribution \(H_0\) that we would like to reject in favor of an alternative hypothesis \(H_a\) given statistical evidence in the form of data samples. For example, if we study the effect of some drug on the amount of sugar in the blood in patients diagnosed with diabetes, we might take two samples out of two distinct populations, one to which we gave a placebo and one to which we gave the treatment. At this point, the goal is to show that the average amount of sugar in the treatment group is lower than the one in the placebo group. Hence, a suitable test for answering this question is given by the following hypotheses:

\[ H_0: \mu_\mathrm{treatment} \ge \mu_\mathrm{placebo} \quad \mbox{against} \quad H_a: \mu_\mathrm{treatment} < \mu_\mathrm{placebo} \]

As suggested by intuition, the alternative hypothesis is first determined on the basis of what we aim at proving and the null hypothesis \(H_0\) is then deduced as the complementary event to \(H_a\).

The permutation framework completely redefines the null and alternative hypotheses with respect to the traditional approach:

- The null hypothesis is
**always the same**for all tests performed in the permutation framework. This is by design. In effect, the idea of using the permutations to approach the null distribution relies on the assumption of data exchangeability under \(H_0\). This means that the null hypothesis always needs to be that the two samples are drawn from the same underlying distribution. Hence, if we have two independent samples \(X_1, \dots, X_{n_x} \stackrel{i.i.d.}{\sim} F_X\) and \(Y_1, \dots, Y_{n_y} \stackrel{i.i.d.}{\sim} F_Y\), the null hypothesis for the two-sample problem is necessarily: \[ H_0: F_X = F_Y. \] - The alternative hypothesis
**is not**the complementary event to \(H_0\). In effect, that would be \(F_X \neq F_Y\). However, there could be millions of reasons for that to be true. In practice, the use of a specific test statistic targets some aspect(s) of the distributions. For instance, if one uses Hotelling’s \(T^2\) statistic, focus is put on finding differences in the first-order moment of the two distributions \(F_X\) and \(F_Y\). - These two differences generate a huge change of paradigm for interpreting the results. In effect, suppose that the permutation test using Hotelling’s \(T^2\) statistic reveals that there is not enough evidence to reject the null hypothesis. This does not imply, by no means, that we can assume that the two samples come from the same distribution, because, for all we know, our data could contain enough evidence to identify differences in variance or higher moments.

Once you have your sample of \(m\)
permutations out the \(m_t\) possible
ones, you can in fact compute the values of as many test statistics
\(T^{(1)}, \dots, T^{(L)}\) as you
want. At this point, you might want to use the unbiased estimator \(\widehat{p_\infty}^{(\ell)} =
\frac{B^{(\ell)}}{m}\) of the p-value \(p_\infty^{(\ell)} = \mathbb{P} \left( T^{(\ell)}
\ge t_\mathrm{obs}^{(\ell)} \right)\) for each test statistic to
produce \(L\) p-value estimates, each
one targeting a different aspect of the distributions under
investigation. Since this evidence has been summarized by p-values, they
are all on the same scale even though they might look at very different
features of the distributions. They can therefore be combined in various
ways to provide a single test statistic value to be used in the testing
procedure. There are several possible **combining
functions** to do this fusion of p-values. The package
**flipr** currently implements:

- Tippett’s combining function: \(\mathrm{Tippett}(p_1, …, p_L) = 1 - \min_{\ell \in 1, \dots, L} p_\ell\); and,
- Fisher’s combining function: \(\mathrm{Fisher}(p_1, …, p_L) = -2 \sum_{\ell=1}^L \log p_\ell\).

The choice of the combining function is made through the optional
argument `combining_function`

which takes a string as value.
At the moment, it accepts either `"tippett"`

or
`"fisher"`

for picking one of the two above-mentioned
combining functions.

Pesarin, Fortunato, and Luigi Salmaso. 2010. “Permutation Tests
for Complex Data,” March. https://doi.org/10.1002/9780470689516.