Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-ß1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial

Arabi, Yaseen M.; Asiri, Ayed Y.; Assiri, Abdullah M.; Aziz Jokhdar, Hani A.; Alothman, Adel; Balkhy, Hanan H.; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M.; Memish, Ziad A.; Ghazal, Sameeh; Al Faraj, Sarah; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Al Mekhlafi, Ghaleb A.; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Almotairi, Abdullah; Al Bshabshe, Ali; Kharaba, Ayman; Jose, Jesna; Al Harthy, Abdulrahman; Al Sulaiman, Mohammed; Mady, Ahmed; Fowler, Robert A.; Hayden, Frederick G.; Al-Dawood, Abdulaziz; Abdelzaher, Mohamed; Bajhmom, Wail; Hussein, Mohamed A.

Several methods could be utilized to build an adaptive trial. However, most of these methods would require one to specify a priori the time and type of adjustments that need to take place in the trial. For a disease such as MERS there are many factors that could limit the ability to specify a priori those elements; thus, the recursive two-stage design is a natural choice. This type of design provides enough flexibility to introduce different adjustments while learning from the observed data without inflating the type I error.