Table 2.

Italian market access and price and reimbursement duration, overall and into subsequent procedural steps (from Step 1 to Step 6^a), in strata of new indications and first indications of the same medicines.

Timeframe of the MA and P&R processesa	Overall new indications (days)						Overall first indication (days)b						p value for comparison
	Nc	Mean	SD	Median	Min	Max	N	Mean	SD	Median	Min	Max
Step 1	52	74	18	71	36	120	28	100	14	99	62	148	<0.001
Step 1.1	39	174	194	95	11	938	13	179	342	81	7	1292	0.249
Step 2	39	114	56	105	12	342	14	109	85	87	45	371	0.196
Step 3	52	61	76	30	0	289	28	124	175	82	0	751	0.211
Step 4	51	186	114	182	11	574	28	119	69	106	12	288	0.010
Step 5	48	42	36	39	1	232	28	41	23	31	3	91	0.971
Step 6	49	47	18	43	19	114	28	16	7	16	2	35	<0.001
Steps 2–6	39	447	125	437	214	811	14	515	205	483	294	920	0.499
Steps 1–6	52	603	224	552	286	1702	28	583	425	458	97	2157	0.025
Steps 3–4	51	252	116	253	64	686	28	237	157	201	12	792	0.248

Step 1: From the CHMP opinion to publication of the marketing authorization in the European OJ; Step 1.1: from the CHMP opinion to the start date (the date when the pharmaceutical company submits the P&R dossier to the AIFA)

Step 2: From the start date (if available) to the opening of the procedure by the scientific commission (CTS)

Step 3: From the date of the CTS opening to the date of the last opinion issued by the CTS (time for the CTS to provide scientific advice on reimbursement of the new indication)

Step 4: From the last CTS opinion until the date of the last CPR opinion (time to conclude the P&R negotiation)

Step 5: From the date of the last CPR opinion to ratification of the P&R by AIFA’s BoD that is required for formal approval of the P&R agreement

Step 6: From the BoD ratification to publication of the AIFA determination in the Italian OJ (i.e., the starting date of reimbursement)

MA market access, P&R price and reimbursement, SD standard deviation, Min minimum, Max maximum, CHMP Committee for Medicinal Products for Human Use, AIFA Italian Medicines Agency, CPR Price and Reimbursement Committee, BoD Board of Directors, OJ Official Journal, CTS Technical-Scientific Committee

^aTimeframes of the Italian MA and P&R processes starting from CHMP opinion

^bThe total number of observations for the first indication negotiated (same medicines considered) is < 52 since the analysis was run through a comparison with a specific internal database created and provided by Pharmalex Italy S.p.a. that tracked P&R timings just for the first indication procedures and had been populated starting from 2016. Therefore records of first indications approved between 2013 and 2016 are missing. The yearly distribution of the Italian OJ publication date for the first indication sample is as follows: 2016: n = 8 (29%); 2017: n = 6 (21%); 2018: n = 8 (29%); 2019: n = 5 (18%); 2020: n = 1 (4%)

^cThe number of observations varies depending on the availability of the data: Steps 1.1/2: n = 13 start dates are missing because AIFA stopped disclosing them for a period of time; Step 4: n = 1 CPR opinion is missing because the price assessment seems to have been skipped, likely because it was not considered necessary to renegotiate the price; Steps 5/6: n = 3 BoD dates are not available probably due to the fact that in all three cases, the new indications had been approved under the same price conditions