MEDLINE search strategies

Phase I:

1 RANDOMIZED CONTROLLED TRIAL.pt.
2 CONTROLLED CLINICAL TRIAL.pt.
3 RANDOMIZED CONTROLLED TRIALS.sh.
4 RANDOM ALLOCATION.sh.
5 DOUBLE BLIND METHOD.sh.
6 SINGLE BLIND METHOD.sh.
7 1 OR 2 OR 3 OR 4 OR 5 OR 6
8 ANIMALS.sh. not HUMANS.sh.
9 7 not 8

Phase II:

10 CLINICAL TRIAL.pt.
11 exp CLINICAL TRIALS/
12 (clin$ adj25 trial$).ti,ab.
13 ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab.
14 PLACEBOS.sh.
15 placebo$.ti,ab.
16 random$.ti,ab.
17 RESEARCH DESIGN.sh.
18 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17
19 18 not 8
20 19 not 9

Phase III:

21 COMPARATIVE STUDY.pt
22 exp EVALUATION STUDIES/
23 FOLLOW UP STUDIES.sh
24 PROSPECTIVE STUDIES.sh.
25 (control$ or prospectiv$ or volunteer$).ti,ab.
26 21 OR 22 OR 23 OR 24 OR 25
27 26 not 8
28 27 not (9 or 20)
29 9 or 20 or 28

Phase IV (gestational trophoblastic tumours)

30 exp gestational trophoblastic neoplasm
31 exp gestational trophoblastic disease
32 invasive mole
33 choriocarcinoma
34 gestational trophoblastic tumo$
35 gestational trophoblastic disease
36 gestational trophoblastic neoplasm$
37 hydatidiform mole
38 persistent trophoblastic disease
39 GTT
40 GTD
41 GTN
42 30 OR 31 OR 32 OR 33 OR 34 OR 35 OR 36 OR 37 OR 38 OR 39 OR 40 OR 41

Phase V (chemotherapy)

43 dt.fs
44 tu.fs
45 exp drug therapy
46 exp antineoplastic agents
47 chemo$
48 methotrexate
49 actinomycin D
50 etoposide
51 cyclophosphamide
52 cisplatin
53 vincristine
54 chlorambucil
55 doxorubicin
56 melphalan
57 hydroxyurea
58 CHAMOCA
59 EMA‐CO
60 MAC
61 EMA
62 VPB
63 EMACE
64 5‐FU‐Adria
65 43 OR 44 OR 45 OR 46 OR 47 OR 48 OR 49 OR 50 OR 51 OR 52 OR 53 OR 54 OR 55 OR 56 OR 57 OR 58 OR 59 OR 60 OR 61 OR 62 OR 63 OR 64

Phase VI ( combining all previous phases)

66 29 AND 42 AND 65

CENTRAL search strategy:
#1 GTT
#2 GTD
#3 GTN
#4 (GESTATIONAL AND TROPHOBLASTIC)AND TUMO*
#5 (GESTATIONAL AND TROPHOBLASTIC) AND DISEASE
#6 (GESTATIONAL AND TROPHOBLASTIC) AND NEOPLAS*
#7INVASIVE MOLE
#8 CHORIOCRACINOMA
#9 HYDATIDIFORM
#10 PERSISTENT TROPHOBLASTIC DISEASE
#11 (OR/ #1‐#10)
#12 METHOTREXATE
#13 Act DINOMYCIN
#14 ETOPSIDE
#15 CYCLOPHOSPHAMIDE
#16 CISPLATIN
#17 VINCRISTINE
#18 CHLORAMBUCIL
#19 DOXORUBICIN
#20 MELPHALAN
#21 HYDROXYUREA
#22 CHAMOCA
#23 EMA‐CO
#24 MAC
#25 EMA
#26 VPB
#27 EMACE
#28 5‐FU‐ADRIA
#29 CHEMO*
#30 THERAPY
#31 TREATMENT
#32 (OR/ #12‐#31)
#33 (#11 AND #32)

Embasesearch strategy:
Study identification:
#1 Clinical trial/
#2 Randomized controlled trials/
#3 Random Allocation/
#4 Single‐Blind Method/
#5 Double‐Blind Method/
#6 Cross‐Over Studies/
#7 Placebos/
#8 Randomi?ed controlled trial$.tw.
#9 RCT.tw.
#10 Random allocation.tw.
#11 Randomly allocated.tw.
#12 Allocated randomly.tw.
#13 (allocated adj2 random).tw.
#14 Single blind$.tw.
#15 Double blind$.tw.
#16 ((treble or triple) adj blind$).tw.
#17 Placebo$.tw.
#18 Prospective Studies/
#19 or/1‐18
#20 Case study/
#21 Case report.tw.
#22 Abstract report/ or letter/
#23 or/20‐22
#24 19 not 23
#25 animal/
#26 human/
#27 25 not 26
#28 24 not 27

Location of gestational trophoblastic tumours:
#29 exp trophoblastic tumours
#30 exp trophoblastic disease
#31 invasive mole
#32 choriocarcinoma
#33 gestational trophoblastic tumo$
#34 gestational trophoblastic disease
#35 gestational trophoblastic neoplasm$
#36 hydatidiform mole
#37 persistent trophoblastic disease
#38 GTT
#39 GTD
#40 GTN
#41 or/ 29‐40

Location of chemotherapy:
#42 exp cancer chemotherapy
#43 exp antineoplastic agents
#44 DT.FS
#45 TU.FS
#46 chemo*
#47 methotrexate
#48 actinomycin D
#49 etopside
#50 cyclophosphamide
#51 cisplatin
#52 vincristine
#53 chlorambucil
#54 doxorubicin
#55 melphalan
#56 hydroxyurea
#57 CHAMOCA
#58 EMA‐CO
#59 MAC
#60 EMA
#61 VPB
#62 EMACE
#63 5‐FU‐Adria
#64 or/42‐63

Combining phases:
#65 #28 and #41and #64

Randomisation

The method of randomisation was noted on the data extraction form. We assessed the randomisation as:

• low risk of bias: e.g. a computer‐generated random sequence or a table of random numbers;

• high risk of bias: e.g. date of birth, clinic id‐number or surname;

• unclear risk of bias: e.g. details not reported.

Allocation concealment

We assessed the concealment of allocation sequence from treatment providers and participants as:

• low risk of bias: e.g. where the allocation sequence could not be foretold;

• high risk of bias: e.g. the computer‐generated random sequence was displayed so treatment providers could see which arm of the trial the next participant was assigned to, or kept in a sealed opaque envelope;

• unclear risk of bias: allocation concealment not reported.

Blinding

We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding would be unlikely to affect results. We assessed blinding separately for different outcomes or classes of outcomes and assessed the methods as:

• low, high or unclear risk of bias for participants;

• low, high or unclear risk of bias for personnel.

Incomplete outcome data

We recorded the proportion of participants whose outcomes were not reported at the end of the study and we noted if loss to follow‐up was not reported.

We assessed methods as:

• low risk of bias, if fewer than 20% of patients were lost to follow‐up and reasons for loss to follow‐up were similar in both treatment arms;

• high risk of bias, if more than 20% of patients were lost to follow‐up or reasons for loss to follow‐up differed between the treatment arms;

• unclear risk of bias if loss to follow‐up was not reported.

Selective reporting

We assessed the methods of outcome reporting as:

• low risk of bias (where it is clear that all of the study’s pre‐specified outcomes and all expected outcomes of interest have been reported);

• high risk of bias (where not all the study’s pre‐specified outcomes were reported; one or more reported primary outcomes were not pre‐specified; outcomes of interest were reported incompletely and so could not be used; study fails to include results of a key outcome that would have been expected to have been reported);

• unclear risk of bias.

Other bias

We described for each included study any important concerns we had about other possible sources of bias. We assessed whether each study was free of other problems that could put it at risk of bias and assessed the risk as follows:

• low risk of other bias;

• high risk of other bias;

• unclear whether there is risk of other bias.