Population intervention comparison

1. Describe each element of the Population intervention comparison outcome(PICO) framework and rewrite the research question in your own words using all elements of the Population intervention comparison outcome framework

2. Using the following design characteristics, please calculate the total sample size (across both arms) for this study:

$$70\%$$response in the intervention arm,$$55\%$$response in the control arm, Clinical Trial Scenario A phase II clinical trial to investigate the efficacy of a novel immunotherapy agent (MSD25678) as a first-line treatment to improve cancer response in patients with advanced lung cancer Information which may be useful to guide your answers: MSD25678 has been shown to be effective in patients with more advanced lung cancer. In this trial it will be tested as a first-line therapy after patients have been newly diagnosed with lung cancer, looking at cancer response, defined as either the cancer having gone away (a complete response) or shrunk (a partial response) vs. no response. All patients will provide written informed consent. MSD25678 is given via intravenous infusion every 4 weeks until progression. A nurse or other trained health professional will administer the medicine in a hospital. It is given through a needle placed into a vein. It must be given slowly, so the needle will have to remain in place for at least 30 to 60 minutes every 4 weeks. For the purposes of this assessment please assume that the control arm is standard chemotherapy. There is no need to be more specific. The trial is randomised, but not blinded. Participants will have$$\mathrm{CT}$$scans to assess response. Scans will be performed at baseline and every 8 weeks while on treatment. Cancer response will be assessed by the clinical team at each participating site. Contraindications to use of MSD25678: The presence of other medical problems may affect the use of this medicine, especially: – Diabetes or – Immune system problems (eg, Crohn’s disease, ulcerative colitis, lupus) or – Infection or – Liver problems or – Lung or breathing problems or – Nervous system problems (eg, Guillain-Barré syndrome, myasthenia gravis) or – Recent organ transplant or Precautions for the use of MSD25678: Receiving this medicine while pregnant can harm an unborn baby. Females who can get pregnant will require a negative pregnancy test before starting this medicine. An effective form of birth control must be used during treatment with this medicine and for at least 5 months after the last. dose. Potential Side Effects of MSD25678 described in the reference safety information (RS1):

common                – Black, tarry stools  – bladder pain        – bloating or swelling of the face,            – bloody or cloudy urine      – blurred vision      – chest tightness            – chills          – constipation        – cough  – diarrhea  – difficult, burning or painful ​      – difficulty in breathing                          – dizziness       – fever         – frequent urge to urinate    – general feeling of tiredness and       – weakness   – headache loss of appetite      – lows of voice     – lower back or side pain      – nuscle aches  urination ​​Less common       – Anxiety        – burning, tingling, numbness or  – chain in the hands, arms, feet, or                       – confusion                     – dark urine  . depressed mood                – difficulty with chewing,  swallowing, or talking  double vision  decreased urine ​ general feeling of discomfort or ​Rare